Use of A Collagen/Elastin Matrix As Transport Carrier System to Transfer Proliferating Epidermal Cells to Human Dermis in Vitro

This in vitro study describes a novel cell culture, transport, and transfer protocol that may be highly suitable for delivering cultured proliferating keratinocytes and melanocytes to large open skin wounds (e.g., burns). We have taken into account previous limitations identified using other keratinocyte transfer techniques, such as regulatory issues, stability of keratinocytes during transport (single cell suspensions undergo terminal differentiation), ease of handling during application, and the degree of epidermal blistering resulting after transplantation (both related to transplanting keratinocyte sheets). Large numbers of proliferating epidermal cells (EC) (keratinocytes and melanocytes) were generated within 10-14 days and seeded onto a three-dimensional matrix composed of elastin and collagen types I, III, and V (Matriderm®), which enabled easy and stable transport of the EC for up to 24 h under ambient conditions. All culture conditions were in accordance with the regulations set by the Dutch Central Committee on Research Involving Human Subjects (CCMO). As an in vitro model system for clinical in vivo transfer, the EC were then transferred from Matriderm onto human acellular dermis during a period of 3 days. After transfer the EC maintained the ability to regenerate into a fully differentiated epidermis containing melanocytes on the human dermis. Proliferating keratinocytes were located in the basal layer and keratin-10 expression was located in differentiating suprabasal layers similar to that found in human epidermis. No blistering was observed (separation of the epidermis from the basement membrane). Keratin-6 expression was strongly upregulated in the regenerating epidermis similar to normal wound healing. In summary, we show that EC-Matriderm contains viable, metabolically active keratinocytes and melanocytes cultured in a manner that permits easy transportation and contains epidermal cells with the potential to form a pigmented reconstructed epidermis. This in vitro study has produced a robust protocol that is ready for clinical studies in the future

‘Missing out’: Reflections on the positioning of ethnographic research within an evaluative framing

Contemporary approaches to evaluating ‘complex’ social and health interventions are opening up spaces for methodologies attuned to examining contextual complexities, such as ethnography. Yet the alignment of the two agendas – evaluative and ethnographic – is not necessarily comfortable in practice. I reflect on experiences of conducting ethnographic research alongside a public health evaluation of a community-based initiative in the UK, using the lens of ‘missing out’ to examine intersections between my own ethnographic concerns and those of the communities under study. I examine potential opportunities posed by the discomfort of ‘missing out’, particularly for identifying the processes and spaces of inclusion and exclusion that contributed both to my ethnographic experiences and to the realities of the communities engaging with the initiative. This reveals productive possibilities for a focus on ‘missing out’ as a form of relating for evaluations of the impacts of such initiatives on health and social inequalities

The precautions of clinical waste: disposable medical sharps in the United Kingdom

This article deals with recent changes in UK guidance on clinical waste, in particular a shift to disposable, single-use instruments and sharps. I use interviews conducted with nurses from a GP practice and two clinical waste managers at alternative treatment and incineration sites as a springboard for reflection on the relationship between the legislation on clinical waste management and its implementation. Scrutinizing the UK guidance, European legislation and World Health Organization principles, I draw out interviewees’ concerns that the changed practices lead to an expansion of the hazardous waste category, with an increased volume going to incineration. This raises questions regarding the regulations’ environmental and health effects, and regarding the precautionary approach embedded in the regulations. Tracing the diverse reverberations of the term ‘waste’ in different points along the journeys made by sharps in particular, and locating these questions in relation to existing literature on waste, I emphasize that public health rationales for the new practices are not made clear in the guidance. I suggest that this relative silence on the subject conceals both the uncertainties regarding the necessity for these means of managing the risks of infectious waste, and the tensions between policies of precautionary public health and environmental sustainability

Anti-angiogenic drugs: direct anti-cancer agents with mitochondrial mechanisms of action

Components of the mitochondrial electron transport chain have recently gained much interest as potential therapeutic targets. Since mitochondria are essential for the supply of energy that is required for both angiogenic and tumourigenic activity, targeting the mitochondria represents a promising potential therapeutic approach for treating cancer. Here we investigate the established anti-angiogenesis drugs combretastatin A4, thalidomide, OGT 2115 and tranilast that we hypothesise are able to exert a direct anti-cancer effect in the absence of vasculature by targeting the mitochondria. Drug cytotoxicity was measured using the MTT assay. Mitochondrial function was measured in intact isolated mitochondria using polarography, fluorimetry and enzymatic assays to measure mitochondrial oxygen consumption, membrane potential and complex I–IV activities respectively. Combretastatin A4, OGT 2115 and tranilast were both shown to decrease mitochondrial oxygen consumption. OGT 2115 and tranilast decreased mitochondrial membrane potential and reduced complex I activity while combretastatin A4 and thalidomide did not. OGT 2115 inhibited mitochondrial complex II–III activity while combretastatin A4, thalidomide and tranilast did not. Combretastatin A4, thalidomide and OGT 2115 induced bi-phasic concentration-dependent increases and decreases in mitochondrial complex IV activity while tranilast had no evident effect. These data demonstrate that combretastatin A4, thalidomide, OGT 2115 and tranilast are all mitochondrial modulators. OGT 2115 and tranilast are both mitochondrial inhibitors capable of eliciting concentration-dependent reductions in cell viability by decreasing mitochondrial membrane potential and oxygen consumption

Story in health and social care

This paper offers a brief consideration of how narrative, in the form of people‟s own stories, potentially figures in health and social care provision as part of the impulse towards patient-centred care. The rise of the epistemological legitimacy of patients‟ stories is sketched here. The paper draws upon relevant literature and original writing to consider the ways in which stories can mislead as well as illuminate the process of making individual treatment care plans

Increased epidermal thickness and abnormal epidermal differentiation in keloid scars

Background: The pathogenesis underlying keloid formation is still poorly understood. Research has focused mostly on dermal abnormalities, while the epidermis has not yet been studied. Objectives: To identify differences within the epidermis of mature keloid scars compared with normal skin and mature normotrophic and hypertrophic scars. Methods: Rete ridge formation and epidermal thickness were evaluated in tissue sections. Epidermal proliferation was assessed using immunohistochemistry (Ki67, keratins 6, 16 and 17) and with an in vitro proliferation assay. Epidermal differentiation was evaluated using immunohistochemistry (keratin 10, involucrin, loricrin, filaggrin, SPRR2, SKALP), reverse-transcriptase polymerase chain reaction (involucrin) and transmission electron microscopy (stratum corneum). Results: All scars showed flattening of the epidermis. A trend of increasing epidermal thickness correlating to increasing scar abnormality was observed when comparing normal skin, normotrophic scars, hypertrophic scars and keloids. No difference in epidermal proliferation was observed. Only the early differentiation marker involucrin showed abnormal expression in scars. Involucrin was restricted to the granular layer in healthy skin, but showed panepidermal expression in keloids. Normotrophic scars expressed involucrin in the granular and upper spinous layers, while hypertrophic scars resembled normotrophic scars or keloids. Abnormal differentiation was associated with ultrastructural disorganization of the stratum corneum in keloids compared with normal skin. Conclusions: Keloids showed increased epidermal thickness compared with normal skin and normotrophic and hypertrophic scars. This was not due to hyperproliferation, but possibly caused by abnormal early terminal differentiation, which affects stratum corneum formation. Our findings indicate that the epidermis is associated with keloid pathogenesis and identify involucrin as a potential diagnostic marker for abnormal scarring

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120

The discursive construction of childhood and youth in AIDS interventions in Lesotho's education sector: Beyond global-local dichotomies

This is the post-print version of this article. The definitive, peer-reviewed and edited version of this article is published in Environment and Planning D,Society and Space 28(5) 791 – 810, 2010, available from the link below. Copyright @ 2010 Pion.In southern Africa interventions to halt the spread of AIDS and address its social impacts are commonly targeted at young people, in many cases through the education sector. In Lesotho, education-sector responses to AIDS are the product of negotiation between a range of ‘local’ and ‘global’ actors. Although many interventions are put forward as government policy and implemented by teachers in schools, funding is often provided by bilateral and multilateral donors, and the international ‘AIDS industry’—in the form of UN agencies and international NGOs—sets agendas and makes prescriptions. This paper analyses interviews conducted with policy makers and practitioners in Lesotho and a variety of documents, critically examining the discourses of childhood and youth that are mobilised in producing changes in education policy and practice to address AIDS. Focusing on bursary schemes, life-skills education, and rights-based approaches, the paper concludes that, although dominant ‘global’ discourses are readily identified, they are not simply imported wholesale from the West, but rather are transformed through the organisations and personnel involved in designing and implementing interventions. Nonetheless, the connections through which these discourses are made, and children are subjectified, are central to the power dynamics of neoliberal globalisation. Although the representations of childhood and youth produced through the interventions are hybrid products of local and global discourses, the power relations underlying them are such that they, often unintentionally, serve a neoliberal agenda by depicting young people as individuals in need of saving, of developing personal autonomy, or of exercising individual rights.RGS-IB

Klimaatverandering in beeld

De aarde met de daarbij behorende klimaatverandering is een onderwerp dat de laatste jaren steeds vaker in zowel de politiek, de media als de publieke opinie naar voren komt. De bezorgdheid die leeft onder wetenschappers over de zogenoemde global warming wordt steeds groter; de wereldwijde klimaatverandering vormt volgens velen een dreiging voor het mensenleven op aarde. Regeringen hebben gereageerd op deze waarschuwing door onder andere veranderingen in wet- en regelgeving en door zich aan te sluiten bij internationale discussies over het fenomeen. De diverse aspecten van de dreigende klimaatverandering en de gevolgen die de klimaatverandering heeft voor de aarde en daardoor voor de mens, zijn niet universeel geaccepteerd als één feit. Zo zijn er wetenschappers die van mening zijn dat de klimaatverandering een grote dreiging vormt voor de mensheid, terwijl andere wetenschappers vinden dat de klimaatverandering problemen kent die door de mensheid te overbruggen zijn. Tevens zijn er verschillende visies betreffende de manier waarop er met de klimaatverandering dient te worden omgegaan en welke oplossingen er moeten worden geboden. De hoofdvraag van mijn onderzoek is: Hoe ziet de fotoberichtgeving over de klimaatverandering in enkele Nederlandse natuurwetenschappelijke tijdschriften en opinietijdschriften eruit in de periode 2000-2008 en hoe verschilt de fotoberichtgeving in deze twee soorten tijdschriften van elkaar? Deze hoofdvraag wordt onderverdeeld in diverse deelvragen die betrekking hebben op de drie delen van mijn masterthesis: het theoretisch kader, de analyse en de comparatieve analyse. Het theoretisch kader behandelt het brede fenomeen klimaatverandering, de verschillende visies worden beschreven en zowel de oorzaken, gevolgen, aanpassingen als oplossingen omtrent klimaatverandering komen aan bod. Door middel van het theoretisch kader wordt tevens duidelijk welke foto’s behoren tot mijn onderzoek; de foto’s die een weergave tonen van de in het theoretisch kader behandelde aspecten van klimaatverandering. Niet alleen klimaatverandering zelf wordt beschreven, maar ook zal ik de verschillende onderzoeken die zijn uitgevoerd naar de representatie van klimaatverandering in de media beschrijven. Deze onderzoeken geven een beeld van onderzoeksbevindingen die ik wellicht in mijn onderzoek tegen kan komen en zijn zodoende een introductie betreffende mijn analyse. Ten slotte komt het fenomeen icoonfoto aan bod in het theoretisch kader. Nadat de diverse analyses zijn gevormd betreffende de fotografische weergave van klimaatverandering, zal namelijk gekeken worden naar de eventueel aanwezige icoonfoto’s betreffende klimaatverandering. De analyse betreft enkele vooraanstaande Nederlandse tijdschriften, namelijk de natuurwetenschappelijke tijdschriften National Geographic en Quest en de opinietijdschriften Elsevier en Vrij Nederland. In de analyse staan de volgende deelvragen centraal: Op welke wijze is de klimaatverandering in de geselecteerde tijdschriften fotografisch weergegeven? Op welke wijze is de klimaatverandering in de geselecteerde tijdschriften tekstueel weergegeven? Naar aanleiding van de analyse zal ik een comparatieve analyse vormen. In deze analyse worden de geselecteerde tijdschriften tegenover elkaar gezet: de twee natuurwetenschappelijke tijdschriften National Geographic en Quest worden tegenover elkaar gezet, net als de twee opinietijdschriften Elsevier en Vrij Nederland. In de conclusie van deze masterthesis worden de onderzoeksbevindingen beknopt samengevat vanuit het oogpunt van de lezer van het desbetreffende tijdschrift. Er wordt gekeken naar de manier waarop de lezer van de vier tijdschriften gedurende de periode 2000-2008 (Quest betreft de periode 2004-2008) wordt geïnformeerd over klimaatverandering door middel van de fotoberichtgeving. Op deze manier vertaalt deze conclusie de onderzoeksbevindingen als het ware naar de praktijk. Hieronder volgen de beknopte conclusies. De lezer van National Geographic krijgt een negatief beeld van het onderwerp klimaatverandering door middel van de fotoberichtgeving doordat de nadruk op oorzaken en gevolgen ligt met betrekking tot voornamelijk de natuur, en doordat de foto’s of negatief of neutraal zijn, en vrijwel nooit positief. De lezer van Quest krijgt vooral beelden te zien van aanpassingen en/of oplossingen en doordat de teneur van de foto’s meer neutraal of positief is, dan negatief, krijgt de Quest-lezer over het algemeen een positief beeld bij het onderwerp klimaatverandering door middel van de fotoberichtgeving. De Quest-lezer ziet welke aanpassingen er mogelijk/nodig zijn en welke oplossingen er zijn tegen klimaatverandering, veel meer dan dat de lezer met negatieve aspecten in aanraking komt, zoals de oorzaken en gevolgen. De lezer van Elsevier krijgt door middel van de fotoberichtgeving over klimaatverandering voornamelijk te maken met oplossingen tegen klimaatverandering, getoond op vooral foto’s van kleine of gemiddelde grootte. De teneur is of neutraal of positief, en vrijwel niet negatief, wat onder andere inhoudt dat de Elsevier-lezer nauwelijks in aanraking komt met negatieve aspecten van klimaatverandering. De lezer van Vrij Nederland komt door middel van de fotoberichtgeving over klimaatverandering voornamelijk met oplossingen in aanraking, neutrale of positieve beelden en opiniefoto’s en wetenschappelijke foto’s overheersen in de fotoberichtgeving over klimaatverandering in Elsevier. De lezer krijgt zodoende een neutraal of positief beeld en ziet nauwelijks de negatieve aspecten, zoals de oorzaken of gevolgen van klimaatverandering. Met mijn onderzoek heb ik diverse aspecten omtrent de fotoberichtgeving over klimaatverandering in vooraanstaande Nederlandse tijdschriften in kaart gebracht. Omdat mijn onderzoek zich richt op een veelzijdig onderwerp dat wordt ge(re)presenteerd via diverse media, is er nog een scala aan vervolgonderzoeken te benoemen en uit te voeren die een toevoeging vormen aan mijn onderzoek