Inflammatory cytokines and peripheral mediators in the pathophysiology of pruritus in cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) includes a diverse group of neoplasms, including mycosis fungoides and Sézary syndrome. One of the earliest and most common symptoms of CTCL is pruritus, which affects up to 88% of patients. The severity of pruritus can range from mild to very debilitating, producing tremendous discomfort and a significant decrease in quality of life. Patients with advanced disease, in particular, may experience a more chronic, intractable pruritus. However, the underlying mechanism of pruritus in CTCL remains unknown. Conventional antipruritic agents, such as antihistamines, gamma-aminobutyric acid analogs and antidepressants, are only partially effective in relieving symptoms, suggesting a more complex, unique pathophysiology. In this review, we summarize the current research on cytokines and peripheral mediators implicated in pruritus in CTCL.

Fully printed high performance humidity sensors based on two-dimensional materials.

Fully printed humidity sensors based on two-dimensional (2D) materials are described. Monolayer graphene oxide (GO) and few-layered black phosphorus (BP) flakes were dispersed in low boiling point solvents suitable for inkjet printing. The humidity sensors were fabricated by printing GO and BP sensing layers on printed silver nanoparticle electrodes. The electrical response of the GO and BP sensors to humidity levels ranges from 11 to 97% relative humidity, which revealed a high capacitance sensitivity of 4.45 × 104 times for the GO sensor and 5.08 × 103 times for the BP sensor at 10 Hz operation frequency. Response/recovery times of the GO and BP sensor were found to be 2.7/4.6 s and 4.7/3.0 s respectively. These sensors also showed sensitive and fast response to a proximal human fingertip, showing potential applications in contactless switching.

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults.

BACKGROUND: T-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults. METHODS: We conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18-46years and 24 subjects aged 50years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18months. FINDINGS: Both vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP+M1 vaccination was significantly higher compared to ChAdOx1 NP+M1. In a mixed regression model, T-cell responses over 18months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP+M1. INTERPRETATION: A two dose heterologous vaccination regimen of MVA/ChAdOx1 NP+M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A. FUNDING SOURCE: Medical Research Council UK, NIHR BMRC Oxford.

Pruritic arthropod bite-like papules in T-cell large granular lymphocytic leukaemia and chronic myelomonocytic leukaemia.

T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features. Because of the rarity of T-LGLL, its cutaneous manifestations are poorly documented, but include vasculitis, vasculopathy, persistent ulcerations, generalized pruritus and disseminated granuloma annulare. Various types of skin lesions have been observed in patients with CMML and reportedly occur in approximately 10% of cases. We report the extraordinary case of a patient with MDS who developed T-LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite-like papules and intractable pruritus.

High magnetic relaxivity in a fluorescent CdSe/CdS/ZnS quantum dot functionalized with MRI contrast molecules.

Light emitting semiconducting quantum dots show great promise as solar cells, optoelectronic devices and multimodal imaging probes. Here we demonstrate successful grafting of a thiol-functionalised GdIII MRI contrast agent onto the surface of core-multishell CdSe/CdS/ZnS quantum dots. The resulting nanoprobe exhibits intense photoluminescence and unprecedentedly large T1 relaxivity of 6800 mM-1 s-1 per nanoparticle due to secure implanting of ca. 620 magnetic centers per quantum dot unit.

"I don't know how I'm still standing" a Bakhtinian analysis of social housing and health narratives in East London.

Housing is a significant determinant of health and substandard housing is a public health issue. East London has long had a shortage of social and affordable housing, worsened in recent years by a combination of stressors. In one of East London's most deprived boroughs, Newham, changes brought about by the 2011 Localism Act and the unique demands of being the host Olympic borough in 2012 have brought considerable pressures to bear on social infrastructure. This paper examines how these pressures were experienced by local residents via their narratives of social housing and health. The data reported here are from a qualitative study comprising two waves of data collection. Narrative family interviews and go-along interviews were conducted with 40 Newham residents at wave one and 28 at wave two. A narrative analysis with a Bakhtinian interpretation was undertaken. This revealed that residents framed experiences of social housing in terms of an inherent system-level ideology based on notions of need and waiting. A particularly striking feature of this ideology was the extent to which descriptions of ill health and impairment were implicated in constructions of housing need; participants directly attributed a range of health complaints to their housing predicaments, including stress, depression, cancer scares, panic attacks and loss of sleep. Understanding the contested ideology of social housing can illuminate both the dynamic processes of social exclusion and the ways in which its subjects seek to resist it.

"Everyone was looking at you smiling": East London residents' experiences of the 2012 Olympics and its legacy on the social determinants of health.

Mega-sporting event regeneration, as a specific approach to urban renewal, uses impending host-city status as a catalyst for revitalisation and has the potential to improve health both through addressing deprivation and by promoting increased sport and physical activity among the host-city's population. This qualitative study explored how hosting of the London 2012 Games impacted upon the way East London residents perceived and experienced the social determinants of health in their local neighbourhood. We conducted narrative family interviews, go-along interviews and video focus group workshops with 66 Newham residents, aged 12-55 years, immediately after the Games. A narrative analytic approach examined accounts of health and wellbeing experiences in terms of neighbourhood change and the spectacle of the Games. Participants of this qualitative study generally welcomed the respite and the unexpected chance to live in a cleaner, safer and more unified environment. However, this positivity was underscored by an acute awareness that this was a very temporary situation and one that was intended to support the event rather than residents.

Hydrodynamic chromatography - inductively coupled plasma mass spectrometry, with post-column injection capability for simultaneous determination of nanoparticle size, mass concentration and particle number concentration (HDC-PCi-ICP-MS).

Hydrodynamic chromatography - inductively coupled plasma mass spectrometry (HDC-ICP-MS) is a technique that is widely used in the size-characterisation of nanoparticles. In this work, a system was modified to facilitate the injection of NIST-traceable standards into the post-column effluent, which then allowed the response from an eluting nanoparticle to be quantified against the response from the post-column standards. Combining the simultaneously acquired particle sizing data and mass concentration data allowed accurate quantification of the particle number concentration to be made in a single analytical run. This unique single-method approach was successfully validated against a nanoparticle system which had previously been characterised in a number of recent peer-reviewed publications. In addition to this, its robustness was assessed using extracts from a study investigating the fate of nanoparticles in sewage sludge, and found to provide much improved data compared to what might have been achieved using an external calibration approach. With in-vial limits of detection of 2 and 10 ng ml(-1) for titanium and silver respectively, it is insufficient for use with environmental waters, but is foreseen as being useful in screening nanoparticle production processes, or in the characterisation of higher concentration materials. As this instrumental configuration is likely to be of use to researchers involved in the general area of quantitative trace element speciation, detailed description of construction of the interface is given as ESI.

Economic-based projections of future land use in the conterminous United States under alternative policy scenarios.

Land-use change significantly contributes to biodiversity loss, invasive species spread, changes in biogeochemical cycles, and the loss of ecosystem services. Planning for a sustainable future requires a thorough understanding of expected land use at the fine spatial scales relevant for modeling many ecological processes and at dimensions appropriate for regional or national-level policy making. Our goal was to construct and parameterize an econometric model of land-use change to project future land use to the year 2051 at a fine spatial scale across the conterminous United States under several alternative land-use policy scenarios. We parameterized the econometric model of land-use change with the National Resource Inventory (NRI) 1992 and 1997 land-use data for 844 000 sample points. Land-use transitions were estimated for five land-use classes (cropland, pasture, range, forest, and urban). We predicted land-use change under four scenarios: business-as-usual, afforestation, removal of agricultural subsidies, and increased urban rents. Our results for the business-as-usual scenario showed widespread changes in land use, affecting 36% of the land area of the conterminous United States, with large increases in urban land (79%) and forest (7%), and declines in cropland (-16%) and pasture (-13%). Areas with particularly high rates of land-use change included the larger Chicago area, parts of the Pacific Northwest, and the Central Valley of California. However, while land-use change was substantial, differences in results among the four scenarios were relatively minor. The only scenario that was markedly different was the afforestation scenario, which resulted in an increase of forest area that was twice as high as the business-as-usual scenario. Land-use policies can affect trends, but only so much. The basic economic and demographic factors shaping land-use changes in the United States are powerful, and even fairly dramatic policy changes, showed only moderate deviations from the business-as-usual scenario. Given the magnitude of predicted land-use change, any attempts to identify a sustainable future or to predict the effects of climate change will have to take likely land-use changes into account. Econometric models that can simulate land-use change for broad areas with fine resolution are necessary to predict trends in ecosystem service provision and biodiversity persistence.

Reducing microbial contamination in storm runoff from high use areas on California coastal dairies.

High use areas are a fundamental part of California coastal dairies and grazing livestock ranches as feeding areas, nurseries, and sick pens. High stocking densities and daily use in these areas lead to soil surfaces devoid of vegetation and covered in manure, with high potential for manure transport during winter rains to receiving waters regulated for shellfish harvesting and recreation. We characterized the association between California's Mediterranean climate and a series of existing and proposed management practices on fecal coliform bacteria (FCB) transport from high use areas on dairies and ranches. Results from 351 storm runoff samples collected below 35 high-use areas indicate that removal of cattle during winter, locating high use areas on level ground, application of straw and seeding, and vegetative buffer strip implementation were significantly associated with FCB concentration and load reductions. These results complement our findings for reductions of specific pathogens in runoff from these areas. These findings have practical significance because they document surface water quality benefits that the studied management practices provide in application on working farms and ranches. This direction is critical and timely for on-farm management efforts seeking to reduce microbial pollution in runoff and comply with indicator bacteria water quality criteria.

Influence of the A and B subunits of cholera toxin (CT) and Escherichia coli toxin (LT) on TNF-alpha release from macrophages.

In this study an in vitro model was developed with the aim of investigating the modulatory effect of cholera toxin (CT) and its counterpart the heat labile toxin of Escherichia coli (LT) on TNF-alpha release induced by murine macrophages and primary human monocytes. Previous studies have demonstrated that the enzymatic activity of CT and LT molecules can inhibit TNF-alpha release by macrophages. The results obtained in this study showed that CT and LT are both, in a dose dependent manner, able either to induce or inhibit TNF-alpha release by murine macrophages and primary human monocytes. The results also showed that recombinant B subunits of CT and LT in the absence of their A subunit induce high levels of TNF-alpha release by macrophages and, in addition, increase the level of TNF-alpha release induced by LPS. The ability of both B subunits (CTB and LTB) in inducing TNF-alpha release by macrophages is not related to the level of LPS contamination, since direct measurements of LPS made in the samples employed in this study showed only traces of LPS (3.4 x 10(-8) EU/ml) which is in our system does not induce TNF-alpha release by macrophages. In contrast to the results obtained with the B subunits, incubation of cells with the A subunit of CT (CTA) inhibit TNF-alpha release induced by native CT, native LT, recombinant LTB and LPS. This inhibitory effect must be related to the activity of the A subunit since viability tests performed in terms of metabolic rate demonstrated that high concentrations of CTA are not toxic to the cells. The data presented herein demonstrate that the A subunits of CT and LT have an inhibitory effect on TNF-alpha release in macrophages, whereas their B subunits have a stimulatory effect on TNF-alpha. The results also suggest that the dose dependent bi-modal effect of native CT and native LT on TNF-alpha release by macrophages is a result of the combined effect of their individual A and B subunits.

Farm factors associated with reducing Cryptosporidium loading in storm runoff from dairies.

A systems approach was used to evaluate environmental loading of Cryptosporidium oocysts on five coastal dairies in California. One aspect of the study was to determine Cryptosporidium oocyst concentrations and loads for 350 storm runoff samples from dairy high use areas collected over two storm seasons. Selected farm factors and beneficial management practices (BMPs) associated with reducing the Cryptosporidium load in storm runoff were assessed. Using immunomagnetic separation (IMS) with direct fluorescent antibody (DFA) analysis, Cryptosporidium oocysts were detected on four of the five farms and in 21% of storm runoff samples overall. Oocysts were detected in 59% of runoff samples collected near cattle less than 2 mo old, while 10% of runoff samples collected near cattle over 6 mo old were positive. Factors associated with environmental loading of Cryptosporidium oocysts included cattle age class, 24 h precipitation, and cumulative seasonal precipitation, but not percent slope, lot acreage, cattle stocking number, or cattle density. Vegetated buffer strips and straw mulch application significantly reduced the protozoal concentrations and loads in storm runoff, while cattle exclusion and removal of manure did not. The study findings suggest that BMPs such as vegetated buffer strips and straw mulch application, especially when placed near calf areas, will reduce environmental loading of fecal protozoa and improve stormwater quality. These findings are assisting working dairies in their efforts to improve farm and ecosystem health along the California coast.

Ability of SPI2 mutant of S. typhi to effectively induce antibody responses to the mucosal antigen enterotoxigenic E. coli heat labile toxin B subunit after oral delivery to humans.

We have evaluated an oral vaccine based on an Salmonella enteric serovar typhi (S. typhi) Ty2 derivative TSB7 harboring deletion mutations in ssaV (SPI-2) and aroC together with a chromosomally integrated copy of eltB encoding the B subunit of enterotoxigenic Escherichia coli heat labile toxin (LT-B) in volunteers. Two oral doses of 10(8) or 10(9)CFU were administered to two groups of volunteers and both doses were well tolerated, with no vaccinemia, and only transient stool shedding. Immune responses to LT-B and S. typhi lipopolysaccharide were demonstrated in 67 and 97% of subjects, respectively, without evidence of anti-carrier immunity preventing boosting of LT-B responses in many cases. Further development of this salmonella-based (spi-VEC) system for oral delivery of heterologous antigens appears warranted.

Changes in the chemical form of selenium observed during the manufacture of a selenium-enriched sourdough bread for use in a human nutrition study.

High-performance liquid chromatography interfaced with inductively coupled plasma mass spectrometry, and hydride generation-inductively coupled plasma mass spectrometry were used, respectively, to investigate changes in both the chemical form and the concentration of selenium during its bio-incorporation and bio-accumulation into rye seedlings. A 60-fold increase in the total level of selenium in the seedlings ('control' biomass = 0.99 mg kg(-1), 'enriched' biomass = 55.27 mg kg(-1)) was accompanied by a change from selenite to several organo-selenium forms, with more than 40% being present as selenomethionine. The seedling biomass was dried, ground and used as an ingredient in the production of a fermented sourdough bread (popular in Poland and many Eastern European countries). The selenium in the resulting bread was also characterized in terms of its speciation, as well as its total selenium content ('control' bread = 0.06 mg kg(-1), 'enriched' bread = 3.56 mg kg(-1)). The breads were then fed to 24 volunteers as part of a human intervention study designed to establish the efficacy of this mode of selenium supplementation. The human study data subsequently showed the bread was a good source of dietary selenium.