The 'Parekh Report' - national identities with nations and nationalism

‘Multiculturalists’ often advocate national identities. Yet few study the ways in which ‘multiculturalists’ do so and in this article I will help to fill this gap. I will show that the Commission for Multi-Ethnic Britain’s report reflects a previously unnoticed way of thinking about the nature and worth of national identities that the Commission’s chair, and prominent political theorist, Bhikhu Parekh, had been developing since the 1970s. This way of thinking will be shown to avoid the questionable ways in which conservative and liberal nationalists discuss the nature and worth of national identities while offering an alternative way to do so. I will thus show that a report that was once criticised for the way it discussed national identities reflects how ‘multiculturalists’ think about national identities in a distinct and valuable way that has gone unrecognised

Challenges in corneal endothelial cell culture

Corneal endothelial cells (CECs) facilitate the function of maintaining the transparency of the cornea. Damage or dysfunction of CECs can lead to blindness, and the primary treatment is corneal transplantation. However, the shortage of cornea donors is a significant problem worldwide. Thus, cultured CEC therapy has been proposed and found to be a promising approach to overcome the lack of tissue supply. Unfortunately, CECs in humans rarely proliferate in vivo and, therefore, can be extremely challenging to culture in vitro. Several promising cell isolation and culture techniques have been proposed. Multiple factors affecting the success of cell expansion including donor characteristics, preservation and isolation methods, plating density, media preparation, trans-differentiation and biomarkers have been evaluated. However, there is no consensus on standard technique for CEC culture. This review aimed to determine the challenges and investigate potential options that would facilitate the standardization of CEC culture for research and therapeutic application

A contextual definition of longitudinal integrated clerkships within the UK and Ireland: a bi-national modified Delphi study

Disagreement exists within the UK and Ireland regarding how Longitudinal Integrated Clerkships should be defined, and the relevance of international definitions. In this modified, online Delphi study, we presented the UK and Ireland experts in Longitudinal Integrated Clerkships with statements drawn from international definitions, published LIC literature, and the research team's experience in this area and asked them to rate their level of agreement with these statements for inclusion in a bi-national consensus definition. We undertook three rounds of the study to try and elicit consensus, making adaptations to statement wording following rounds 1 and 2 to capture participants' qualitative free text-comments, following the third and final round, nine statements were accepted by our panel, and constitute our proposed definition of Longitudinal Integrated Clerkships within the UK and Ireland. This definitional statement corresponds with some international literature but offers important distinctions, which account for the unique context of healthcare (particularly primary care) within the UK and Ireland (for example, the lack of time-based criteria within the definition). This definition should allow UK and Irish researchers to communicate more clearly with one another regarding the benefits of LICs and longitudinal learning and offers cross-national collaborative opportunities in LIC design, delivery and evaluation

Adam Smith and Colonialism

In the context of debates about liberalism and colonialism, the arguments of Adam Smith have been taken as illustrative of an important line of anti-colonial liberal thought. The reading of Smith presented here challenges this interpretation. It argues that Smith’s opposition to colonial rule derived largely from its impact on the metropole, rather than on its impact on the conquered and colonised; that Smith recognised colonialism had brought ‘improvement’ in conquered territories and that Smith struggled to balance recognition of moral diversity with a universal moral framework and a commitment to a particular interpretation of progress through history. These arguments have a wider significance as they point towards some of the issues at stake in liberal anti-colonial arguments more generally

Community-engaged primary care medical education

BACKGROUND: Community-engaged medical education (CEME) requires medical schools to partner with local communities to help address community priorities, whilst enhancing the learning experiences of students. Current literature on CEME has focused on evaluating its effects on students; however, there remains a gap in exploring whether CEME initiatives can have a sustainable impact for communities. APPROACH: The Community Action Project (CAP) at Imperial College London, is an eight-week, community-engaged, quality improvement project for Year 3 medical students. Students initially consult with clinicians, patients and wider community stakeholders to understand local needs and assets, and identify a health priority to address. They then work with relevant stakeholders to design, implement and evaluate a project to help address their identified priority. EVALUATION: All CAPs (n = 264) completed in the 2019-2021 academic years were evaluated for evidence of several key areas, including community engagement and sustainability. 91% of projects evidenced a needs analysis, 71% demonstrated patient involvement in their development, and 64% demonstrated sustainable impacts from their projects. Analysis revealed the topics frequently addressed, and the formats used by students. Two CAPs are described in more detail to demonstrate their community impact. IMPLICATIONS: The CAP demonstrates how the principles of CEME (meaningful community engagement and social accountability) can lead to sustainable benefits for local communities through purposeful collaboration with patients and local communities. Strengths, limitations and future directions are highlighted

GW627368X inhibits proliferation and induces apoptosis in cervical cancer by interfering with EP4/EGFR interactive signaling

PGE2, the major product of cyclooxygenases implicated in carcinogenesis, is significantly upregulated in cervical cancer. PGE2 via prostanoid receptor EP4 stimulates proliferation and motility while inhibiting apoptosis and immune surveillance. It promotes angiogenesis by stimulating the production of pro-angiogenic factors. The present study demonstrates GW627368X, a highly selective competitive EP4 antagonist, which hinders cervical cancer progression by inhibiting EP4/Epithelial Growth Factor Receptor (EGFR) interactive signaling. GW627368X reduced Protein Kinase A (PKA) phosphorylation which in turn leads to decreased cAMP response element-binding protein (CREB) activation. Decreased PKA phosphorylation also directly enhanced Bax activity and in part reduced glycogen synthase kinase 3 (GSK3)β phosphorylation. Owing to the interactive signaling between EP4 and EGFR, GW627368X lowered EGFR phosphorylation in turn reducing Akt, Mitogen-activated Protein Kinase (MAPK) and GSK3β activity significantly. Sublethal dose of GW627368X was found to reduce the nuclear translocation of β-catenin in a time dependent manner along with time-dependent decrease in cytoplasmic as well as whole-cell β-catenin. Decreased CREB and β-catenin transcriptional activity restricts the aberrant transcription of key genes like EP4, cyclooxygenase (COX)-2, vascular endothelial growth factor and c-myc, which ultimately control cell survival, proliferation and angiogenesis. Reduced activity of EGFR resulted in enhanced expression of 15-hydroxyprostaglandin dehydrogenase increasing PGE2 degradation thereby blocking a positive feedback loop. In xenograft model, dose-dependent decrease in cancer proliferation was observed characterized by reduction in tumor mass and volume and a marked decrease in Ki67 expression. A diminished CD31 specific staining signified decreased tumor angiogenesis. Reduced expression of pAkt, pMAPK, pEGFR and COX-2 validated in vitro results. GW627368X therefore effectively inhibits tumor survival, motility, proliferation and angiogenesis by blocking EP4/EGFR interactive signaling. EP4 is a potent therapeutic target in cervical cancer and can be explored in combination with conventional therapies to attain superior outcomes and to overcome complications associated with organ toxicities, therapeutic resistance and disease relapse

Quantitative nanohistological investigation of scleroderma: An atomic force microscopy-based approach to disease characterization

Scleroderma (or systemic sclerosis, SSc) is a disease caused by excess crosslinking of collagen. The skin stiffens and becomes painful, while internally, organ function can be compromised by the less elastic collagen. Diagnosis of SSc is often only possible in advanced cases by which treatment time is limited. A more detailed analysis of SSc may provide better future treatment options and information of disease progression. Recently, the histological stain picrosirius red showing collagen register has been combined with atomic force microscopy (AFM) to study SSc. Skin from healthy individuals and SSc patients was biopsied, stained and studied using AFM. By investigating the crosslinking of collagen at a smaller hierarchical stage, the effects of SSc were more pronounced. Changes in morphology and Young’s elastic modulus were observed and quantified; giving rise to a novel technique, we have termed “quantitative nanohistology”. An increase in nanoscale stiffness in the collagen for SSc compared with healthy individuals was seen by a significant increase in the Young’s modulus profile for the collagen. These markers of stiffer collagen in SSc are similar to the symptoms experienced by patients, giving additional hope that in the future, nanohistology using AFM can be readily applied as a clinical tool, providing detailed information of the state of collagen

Cell Membrane Penetration without Pore Formation : Chameleonic Properties of Dendrimers in Response to Hydrophobic and Hydrophilic Environments

The mechanism by which cell-penetrating peptides and antimicrobial peptides cross plasma membranes is unknown, as is how cell-penetrating peptides facilitate drug delivery, mediating the transport of small molecules. Once nondisruptive and nonendocytotic pathways are excluded, pore formation is one of the proposed mechanisms, including toroidal, barrel-stave, or carpet models. Spontaneous pores are observed in coarse-grained simulations and less often in molecular dynamics simulations. While pores are widely assumed and inferred, there is no unambiguous experimental evidence of the existence of pores. Some recent experimental studies contradict the mechanistic picture of pore formation, however, highlighting the possibility of a direct translocation pathway that is both nondisruptive and nonendocytotic. In this work, a model is proposed a model for peptide (linear and dendritic) translocation which does not require the presence of pores and which potentially accords with such experiments. It is suggested that a charged peptide, as it experiences an increasingly hydrophobic environment within the membrane surface, can utilize a proton chain transfer mechanism to shed its protons to counter ions or potentially phospholipid head groups in the membrane skin region, thereby becoming compatible with the hydrophobic interior of the membrane. This increases the likelihood to move into the highly hydrophobic core of the membrane and ultimately reach the opposite leaflet to re-acquire protons again, suggesting a potential "chameleon" mechanism for non-disruptive and non-endocytotic membrane translocation. The molecular dynamics simulations reveal stability of peptide bridges joining two membrane leaflets and demonstrate that this can facilitate cross-membrane transport of small drug molecules.Peer reviewe