Effects of rituximab-based B-cell depletion therapy on skin manifestations of lupus erythematosus--report of 17 cases and review of the literature

Cutaneous manifestations occur frequently in systemic lupus erythematosus (SLE) and are pathognomonic in subacute-cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Although B-cell depletion therapy (BCDT) has demonstrated efficacy in SLE with visceral involvement, its usefulness for patients with predominant skin manifestations has not been fully established. In this single-centre, retrospective study 14 consecutive SLE, one CCLE and two SCLE patients with recalcitrant skin involvement were treated with 2 × rituximab 1 g, and 1 × cyclophosphamide 750 mg. Six months after BCDT, nine of 17 (53%) patients were in complete (CR) or partial remission (PR). Relapses occurred in 12 patients (71%) at a mean time of 10 ± 1.8 months after BCDT. A second cycle of BCDT achieved a more sustained remission in seven of nine patients (78%) lasting for a mean time of 18.4 ± 2.7 months. Minor adverse events were experienced by three patients. Mean follow-up was 30 months. Our own results and the literature review demonstrate that BCDT based on rituximab is well tolerated and may be effective for cutaneous lesions of lupus erythematosus. Randomized controlled trials are necessary to further evaluate the value of BCDT for this group of patients

Robert Burns: Recovering Scotland's Memory of the Black Atlantic

This article contributes to the reassessment of Scottish history and identity in light of the recovery of its connections with black Atlantic issues such as slavery and empire. The ‘paradox’ of the national bard seeking employment as a book-keeper on Jamaica remains an uncomfortable area for modern Scotland. This article considers Burns's biographical and textual (dis-)entanglement with the Caribbean in relation to the subsequent competition over his memory. It reads Robert Burns as a lieu de mémoire (Pierre Nora) that opens up a conflicted account of the nature of free labour ideology, slavery and abolition in the late eighteenth century

Established maternal obesity in the rat reprograms hypothalamic appetite regulators and leptin signaling at birth

Objective: Key appetite regulators and their receptors are already present in the fetal hypothalamus, and may respond to hormones such as leptin. Intrauterine food restriction or hyperglycemia can reprogram these circuits, possibly predisposing individuals to adverse health outcomes in adulthood. Given the global obesity epidemic, maternal overweight and obesity is becoming more prevalent. Earlier, we observed rapid growth of pups from obese dams during the suckling period. However, it is unclear whether this is because of alterations in leptin and hypothalamic appetite regulators at birth. Design: Female Sprague-Dawley rats were fed palatable high-fat diet (HFD) or chow for 5 weeks to induce obesity before mating. The same diet continued during gestation. At day 1, after birth, plasma and hypothalamus were collected from male and female pups. Measurements: Body weight and organ mass were recorded. Leptin and insulin levels were measured in the plasma by radioimmunoassay. Hypothalamic mRNA expression of neuropeptide-Y (NPY), pro-opiomelanocortin, leptin receptor and its downstream signal, STAT3 (signal transducer and activator of transcription 3), were measured using real-time PCR. Results: Body and organ weights of pups from obese dams were similar to those from lean dams, across both genders. However, plasma leptin levels were significantly lower in offspring from obese dams (male: 0.53±0.13 vs 1.05±0.21 ng ml-1; female: 0.33±0.09 vs 2.12±0.57 ng ml-1, respectively; both P<0.05). Hypothalamic mRNA expression of NPY, pro-opiomelanocortin, leptin receptor and STAT3 were also significantly lower in pups from obese dams. Conclusion: Long-term maternal obesity, together with lower leptin levels in pups from obese dams may contribute to the lower expression of key appetite regulators on day 1 of life, suggesting altered intrauterine neuron development in response to intrauterine overnutrition, which may contribute to eating disorders later in life. © 2009 Macmillan Publishers Limited All rights reserved

Maternal overnutrition impacts offspring adiposity and brain appetite markers-modulation by postweaning diet

Maternal obesity has long-term consequences for the development of hypothalamic neurones involved in energy homeostasis and the metabolic profile in offspring. In the present study, we compared the effects of maternal obesity induced by longstanding high-fat diet (HFD) with milder postnatal overfeeding during suckling induced by litter size reduction. Female Sprague-Dawley rats consumed chow (C) or HFD. On postnatal day 1, litters from chow dams were adjusted to three per dam (small litter, CS) versus 12 control (normal litter, CN). Litters from HFD dams were adjusted to 12 per dam and fed HFD after weaning to induce obesity (HN). Thus, two degrees of maternal overnutrition were produced (CS and HN). To test whether postweaning diet can amplify the effects of maternal obesity, male offspring weaned onto chow or HFD were followed to 21 weeks. Maternal postnatal overnutrition (CS) and HFD-induced maternal obesity (HN) increased body weight and fat mass in offspring compared to those from control dams (CN). Significant glucose intolerance was induced by both degrees of maternal overnutrition, but only in offspring consuming HFD. HFD-induced maternal obesity (HN) was linked to increased offspring leptin, insulin, lipids, insulin resistance and hyperphagia, and was exaggerated by postweaning HFD. No effect of maternal postnatal overnutrition (CS) was seen on these parameters. Hypothalamic signal transducer and activator of transcription-3 and suppressor of cytokine signalling-3 mRNA were significantly elevated by maternal HFD (HN) in the HFD-fed offspring. The data obtained suggest that even mild maternal overnutrition (CS) led to increased adiposity, glucose intolerance and altered brain appetite regulators in offspring. A greater impact of HFD-induced maternal obesity was evident. Marked additive effects were observed when animals consumed a HFD postweaning. © 2010 The Authors. Journal Compilation © 2010 Blackwell Publishing Ltd

Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions

Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development

New Approaches for Teaching Advertising: Looking through the Lens of Social Justice to Affect Career Behaviors and Choices

This exploratory study reviewed how a way of teaching advertising and strategic communication through the lens of social justice and as an active agent to impact society influenced student perspectives. Weaving together engaged scholarship and engagement of hope as a framework for investigation, an introductory advertising course was designed to incorporate social justice, diversity, equity, and inclusion (DEI). Students were interviewed about their learnings, feelings, and career hopes and choices. Assignments and year end reflections were also examined for ideas of social justice and pedagogical approaches. Findings indicate students are knowledgeable of the power and influence of advertising and are sensitive to social justice and DEI issues and the role of brands advocating these ideas. A structure for emphasizing social justice in an introductory advertising course is offered

Pattern of access to cafeteria-style diet determines fat mass and degree of spatial memory impairments in rats.

Repeated 'cycling' between healthy and unhealthy eating is increasingly common but the effects of such cycling on cognitive function are unknown. Here we tested the effects of cycling between chow and a cafeteria diet (CAF) rich in saturated fat and refined carbohydrates on fat mass and place recognition memory in rats. Rats fed the chow diet (control group) were compared with groups fed CAF for either: 3 consecutive days per week followed by 4 days of chow, (3CAF:4CHOW group); 5 consecutive days per week followed by 2 days of chow (5CAF:2CHOW group); or 7 days per week (7CAF group). Total days of exposure to CAF were matched between the latter groups by staggering the introduction of CAF diet. After 16-18 days of CAF, spatial recognition memory was significantly worse in the 7CAF group relative to controls. After 23-25 days of CAF, both the 7CAF and 5CAF:2CHOW groups, but not the 3CAF:4CHOW group, were impaired relative to controls, mirroring changes in fat mass measured by EchoMRI. CAF feeding did not affect object recognition memory or total exploration time. These results indicate that even when matching total exposure, the pattern of access to unhealthy diets impairs spatial memory in a graded fashion

INTEREST: INteractive Tool for Exploring REsults from Simulation sTudies

Simulation studies allow us to explore the properties of statistical methods. They provide a powerful tool with a multiplicity of aims; among others: evaluating and comparing new or existing statistical methods, assessing violations of modelling assumptions, helping with the understanding of statistical concepts, and supporting the design of clinical trials. The increased availability of powerful computational tools and usable software has contributed to the rise of simulation studies in the current literature. However, simulation studies involve increasingly complex designs, making it difficult to provide all relevant results clearly. Dissemination of results plays a focal role in simulation studies: it can drive applied analysts to use methods that have been shown to perform well in their settings, guide researchers to develop new methods in a promising direction, and provide insights into less established methods. It is crucial that we can digest relevant results of simulation studies. Therefore, we developed INTEREST: an INteractive Tool for Exploring REsults from Simulation sTudies. The tool has been developed using the Shiny framework in R and is available as a web app or as a standalone package. It requires uploading a tidy format dataset with the results of a simulation study in R, Stata, SAS, SPSS, or comma-separated format. A variety of performance measures are estimated automatically along with Monte Carlo standard errors; results and performance summaries are displayed both in tabular and graphical fashion, with a wide variety of available plots. Consequently, the reader can focus on simulation parameters and estimands of most interest. In conclusion, INTEREST can facilitate the investigation of results from simulation studies and supplement the reporting of results, allowing researchers to share detailed results from their simulations and readers to explore them freely