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The collection of antiquities of the American Academy in Rome
The foundation of the American Academy in Rome dates back more than one hundred years to the early decades of the last century. Over the years, the Academy has acquired a study collection of material goods from antiquity, including coins, statues and figurines, lamps, stucco and other architectural fragments, jewelry, and inscriptions. While most are Roman in origin, some pieces are Greek or Etruscan. Some were gifts, others come from long-ago excavations, a few were bought. The Collection of Antiquities of the American Academy in Rome, the latest addition to the Supplements to the Memoirs of the American Academy in Rome series, focuses on highlights of the collection.
Book
Psychedelics for the Treatment of Obsessive–Compulsive Disorder: Efficacy and Proposed Mechanisms
Abstract
Psychedelics are emerging as potential treatments for a range of mental health conditions, including anxiety and depression, treatment-resistant depression, and substance use disorders. Recent studies have also suggested that the psychedelic psilocybin may be able to treat obsessive–compulsive disorder (OCD). Since the 1960s, case studies have reported improvements to obsessive and compulsive behaviors in patients taking psychedelics recreationally. The effects of psilocybin were then systematically assessed in a small, open-label trial in 2006, which found that psilocybin significantly reduced the symptoms of OCD. Reduced compulsive behaviors have also been seen in rodent models of OCD after administration of psilocybin. Nonetheless, the mechanisms underlying the effects of psychedelics for OCD are unclear, with hypotheses including their acute pharmacological effects, changes in neuroplasticity and resting state neural networks, and their psychological effects. This review will evaluate the evidence supporting the theory that psychedelics can be used for the treatment of OCD, as well as the data regarding claims about their mechanisms. It will also discuss issues with the current evidence and the ongoing trials of psilocybin that aim to address these knowledge gaps.
Journal Article
Camping with Jesus: Theologically Reflecting on Evangelical Christian Festivals
Attending a Christian summer camp or festival is a regular feature of many evangelical church calendars within the UK. This article uses a practical theology approach to explore definitions and distinctives of evangelical camping, both within the literature on evangelical camping and through examining the websites and publicity materials of three specific camps—New Wine, Big Church Festival and Newday Generation. The analysis highlights the significance placed upon the location, size, rhythms and purposes of gathering in the festivals’ self-understandings. This leads into a theological reflection upon the biblical festival of Sukkot to examine the ways in which God’s work might be disclosed through the practice of evangelical camping. Three pairs of themes emerge from the comparison: located and temporal, secular and religious, and rejoicing and re-examining. These themes are drawn upon to propose ways in which God might be at work in the social world disrupting a sense of permanence, blurring the boundaries between faith and the world, and calling people into radical solidarity with creation and with the marginalized. Finally, suggested actions are proposed as to how evangelical festivals may better respond to God’s disclosure.
Journal Article
Rodent Models of Alzheimer’s Disease: Past Misconceptions and Future Prospects
Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no effective treatments, not least due to the lack of authentic animal models. Typically, rodent models recapitulate the effects but not causes of AD, such as cholinergic neuron loss: lesioning of cholinergic neurons mimics the cognitive decline reminiscent of AD but not its neuropathology. Alternative models rely on the overexpression of genes associated with familial AD, such as amyloid precursor protein, or have genetically amplified expression of mutant tau. Yet transgenic rodent models poorly replicate the neuropathogenesis and protein overexpression patterns of sporadic AD. Seeding rodents with amyloid or tau facilitates the formation of these pathologies but cannot account for their initial accumulation. Intracerebral infusion of proinflammatory agents offer an alternative model, but these fail to replicate the cause of AD. A novel model is therefore needed, perhaps similar to those used for Parkinson’s disease, namely adult wildtype rodents with neuron-specific (dopaminergic) lesions within the same vulnerable brainstem nuclei, ‘the isodendritic core’, which are the first to degenerate in AD. Site-selective targeting of these nuclei in adult rodents may recapitulate the initial neurodegenerative processes in AD to faithfully mimic its pathogenesis and progression, ultimately leading to presymptomatic biomarkers and preventative therapies.
Journal Article
Iron Deficiency Impairs Intra-Hepatic Lymphocyte Mediated Immune Response
Hepatic expression of iron homeostasis genes and serum iron parameters predict the success of immunosuppression withdrawal following clinical liver transplantation, a phenomenon known as spontaneous operational tolerance. In experimental animal models, spontaneous liver allograft tolerance is established through a process that requires intra-hepatic lymphocyte activation and deletion. Our aim was to determine if changes in systemic iron status regulate intra-hepatic lymphocyte responses. We used a murine model of lymphocyte-mediated acute liver inflammation induced by Concanavalin A (ConA) injection employing mice fed with an iron-deficient (IrDef) or an iron-balanced diet (IrRepl). While the mild iron deficiency induced by the IrDef diet did not significantly modify the steady state immune cell repertoire and systemic cytokine levels, it significantly dampened inflammatory liver damage after ConA challenge. These findings were associated with a marked decrease in T cell and NKT cell activation following ConA injection in IrDef mice. The decreased liver injury observed in IrDef mice was independent from changes in the gut microflora, and was replicated employing an iron specific chelator that did not modify intra-hepatic hepcidin secretion. Furthermore, low-dose iron chelation markedly impaired the activation of isolated T cells in vitro. All together, these results suggest that small changes in iron homeostasis can have a major effect in the regulation of intra-hepatic lymphocyte mediated responses.
Journal Article
Revised Phylogeny of the Cellulose Synthase Gene Superfamily
Cell walls are crucial for the integrity and function of all land plants and are of central importance in human health, livestock production, and as a source of renewable bioenergy. Many enzymes that mediate the biosynthesis of cell wall polysaccharides are encoded by members of the large cellulose synthase (CesA) gene superfamily. Here, we analyzed 29 sequenced genomes and 17 transcriptomes to revise the phylogeny of the CesA gene superfamily in angiosperms. Our results identify ancestral gene clusters that predate the monocot-eudicot divergence and reveal several novel evolutionary observations, including the expansion of the Poaceae-specific cellulose synthase-like CslF family to the graminids and restiids and the characterization of a previously unreported eudicot lineage, CslM, that forms a reciprocally monophyletic eudicot-monocot grouping with the CslJ clade. The CslM lineage is widely distributed in eudicots, and the CslJ clade, which was thought previously to be restricted to the Poales, is widely distributed in monocots. Our analyses show that some members of the CslJ lineage, but not the newly identified CslM genes, are capable of directing (1,3;1,4)-𝛽-glucan biosynthesis, which, contrary to current dogma, is not restricted to Poaceae.
Journal Article
Support for hospital doctors’ workplace well-being in England: the Care Under Pressure 3 realist evaluation
IntroductionThe vital role of medical workforce well-being for improving patient experience and population health while assuring safety and reducing costs is recognised internationally. Yet the persistence of poor well-being outcomes suggests that current support initiatives are suboptimal. The aim of this research study was to work with, and learn from, diverse hospital settings to understand how to optimise strategies to improve doctors’ well-being and reduce negative impacts on the workforce and patient care.MethodsRealist evaluation consistent with the Realist And Meta-narrative Evidence Synthesis: Evolving Standards (RAMESES) II quality standards. Realist interviews (n=124) with doctors, well-being intervention implementers/practitioners and leaders in eight hospital settings (England) were analysed using realist logic.ResultsThere were four key findings, underpinned by 21 context-mechanism-outcome configurations: (1) solutions needed to align with problems, to support doctor well-being and avoid harm to doctors; (2) doctors needed to be involved in creating solutions to their well-being problems; (3) doctors often did not know what support was available to help them with well-being problems and (4) there were physical and psychological barriers to accessing well-being support.Discussion and conclusionDoctors are mandated to ‘first, do no harm’ to their patients, and the same consideration should be extended to doctors themselves. Since doctors can be harmed by poorly designed or implemented well-being interventions, new approaches need careful planning and evaluation. Our research identified many ineffective or harmful interventions that could be stopped. The findings are likely transferable to other settings and countries, given the realist approach leading to principles and causal explanations.
Journal Article
Rebound activation of 5-HT neurons following SSRI discontinuation
Cessation of therapy with a selective serotonin (5-HT) reuptake inhibitor (SSRI) is often associated with an early onset and disabling discontinuation syndrome, the mechanism of which is surprisingly little investigated. Here we determined the effect on 5-HT neurochemistry of discontinuation from the SSRI paroxetine. Paroxetine was administered repeatedly to mice (once daily, 12 days versus saline controls) and then either continued or discontinued for up to 5 days. Whereas brain tissue levels of 5-HT and/or its metabolite 5-HIAA tended to decrease during continuous paroxetine, levels increased above controls after discontinuation, notably in hippocampus. In microdialysis experiments continuous paroxetine elevated hippocampal extracellular 5-HT and this effect fell to saline control levels on discontinuation. However, depolarisation (high potassium)-evoked 5-HT release was reduced by continuous paroxetine but increased above controls post-discontinuation. Extracellular hippocampal 5-HIAA also decreased during continuous paroxetine and increased above controls post-discontinuation. Next, immunohistochemistry experiments found that paroxetine discontinuation increased c-Fos expression in midbrain 5-HT (TPH2 positive) neurons, adding further evidence for a hyperexcitable 5-HT system. The latter effect was recapitulated by 5-HT 1A receptor antagonist administration although gene expression analysis could not confirm altered expression of 5-HT 1A autoreceptors following paroxetine discontinuation. Finally, in behavioural experiments paroxetine discontinuation increased anxiety-like behaviour, which partially correlated in time with the measures of increased 5-HT function. In summary, this study reports evidence that, across a range of experiments, SSRI discontinuation triggers a rebound activation of 5-HT neurons. This effect is reminiscent of neural changes associated with various psychotropic drug withdrawal states, suggesting a common unifying mechanism.
Journal Article
The interplay between sex, time of day, fasting status, and their impact on cardiac mitochondrial structure, function, and dynamics
Mitochondria morphology and function, and their quality control by mitophagy, are essential for heart function. We investigated whether these are influenced by time of the day (TOD), sex, and fed or fasting status, using transmission electron microscopy (EM), mitochondrial electron transport chain (ETC) activity, and mito-QC reporter mice. We observed peak mitochondrial number at ZT8 in the fed state, which was dependent on the intrinsic cardiac circadian clock, as hearts from cardiomyocyte-specific BMAL1 knockout (CBK) mice exhibit different TOD responses. In contrast to mitochondrial number, mitochondrial ETC activities do not fluctuate across TOD, but decrease immediately and significantly in response to fasting. Concurrent with the loss of ETC activities, ETC proteins were decreased with fasting, simultaneous with significant increases of mitophagy, mitochondrial antioxidant protein SOD2, and the fission protein DRP1. Fasting-induced mitophagy was lost in CBK mice, indicating a direct role of BMAL1 in regulating mitophagy. This is the first of its kind report to demonstrate the interactions between sex, fasting, and TOD on cardiac mitochondrial structure, function and mitophagy. These studies provide a foundation for future investigations of mitochondrial functional perturbation in aging and heart diseases.
Journal Article
Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation
Rationale
Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation.
Objectives
We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice.
Methods
Male mice received paroxetine (10 mg/kg/day,
s.c.
) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system.
Results
Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation.
Conclusions
This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.
Journal Article