Aims/hypothesis
The innate immune cells, invariant natural killer T cells (iNKT cells), are implicated in the pathogenesis of psoriasis, an inflammatory condition associated with obesity and other ...metabolic diseases, such as diabetes and dyslipidaemia. We observed an improvement in psoriasis severity in a patient within days of starting treatment with an incretin-mimetic, glucagon-like peptide-1 (GLP-1) receptor agonist. This was independent of change in glycaemic control. We proposed that this unexpected clinical outcome resulted from a direct effect of GLP-1 on iNKT cells.
Methods
We measured circulating and psoriatic plaque iNKT cell numbers in two patients with type 2 diabetes and psoriasis before and after commencing GLP-1 analogue therapy. In addition, we investigated the in vitro effects of GLP-1 on iNKT cells and looked for a functional GLP-1 receptor on these cells.
Results
The Psoriasis Area and Severity Index improved in both patients following 6 weeks of GLP-1 analogue therapy. This was associated with an alteration in iNKT cell number, with an increased number in the circulation and a decreased number in psoriatic plaques. The GLP-1 receptor was expressed on iNKT cells, and GLP-1 induced a dose-dependent inhibition of iNKT cell cytokine secretion, but not cytolytic degranulation in vitro.
Conclusions/interpretation
The clinical effect observed and the direct interaction between GLP-1 and the immune system raise the possibility of therapeutic applications for GLP-1 in inflammatory conditions such as psoriasis.
This paper investigates the β-phase depletion behaviour during oxidation of free-standing CoNiCrAlY (Co–31.7%Ni–20.8%Cr–8.1%Al–0.5%Y, all in wt.%) bond coats prepared by high velocity oxy-fuel (HVOF) ...thermal spraying. The microstructure of the coatings was characterised using scanning electron microscopy with energy dispersive X-ray (EDX) analysis and electron backscatter diffraction (EBSD). It comprises a two phase structure of fcc γ-Ni and bcc β-NiAl, with grain sizes varying largely from 0.5 to 2μm for both phases. Isothermal oxidation tests of the free-standing coatings were carried out at 1100°C for times up to 250h. The β phase depletion behaviour at the surface was measured and was also simulated using Thermo-Calc and DICTRA software. An Al flux function derived from an oxide growth model was employed as the boundary condition in the diffusion model. The diffusion calculations were performed using the TTNi7 thermodynamic database together with the MOB2 mobility database. Reasonable agreement was achieved between the measured and the predicted element concentration and phase fraction profiles after various time periods. Grain boundary diffusion is likely to be important to element diffusion in this HVOF sprayed CoNiCrAlY coating due to the sub-micron grain size.
•A fine grain structure was found in this HVOF sprayed CoNiCrAlY coating.•The width of the β depletion zone was significantly affected by surface roughness.•β-phase depletion behaviour during oxidation was modelled.•An initial β depletion zone was considered.•Grain boundary diffusion has a significant effect on the apparent diffusion.
Summary
This pilot and feasibility study evaluated wrist‐worn accelerometers to measure recovery from day‐case surgery in comparison with daily quality of recovery‐15 scores. The protocol was ...designed with extensive patient and public involvement and engagement, and delivered by a research network of anaesthesia trainees. Forty‐eight patients recruited through pre‐operative assessment clinics wore wrist accelerometers for 7 days before (pre‐operative) and immediately after elective surgery (early postoperative), and again at 3 months (late postoperative). Validated activity and quality of recovery questionnaires were administered. Raw accelerometry data were archived and analysed using open source software. The mean (SD) number of valid days of accelerometer wear per participant in the pre‐operative, early and late postoperative periods were 5.4 (1.7), 6.6 (1.1) and 6.6 (1.0) days, respectively. On the day after surgery, Euclidian norm minus one (a summary measure of raw accelerations), step count, light physical activity and moderate/vigorous physical activity decreased to 57%, 47%, 59% and 35% of baseline values, respectively. Activity increased progressively on a daily basis but had not returned to baseline values by 7 days. Patient questionnaires suggested subjective recovery by postoperative day 3 to 4; however, accelerometry data showed that activity levels had not returned to baseline at this point. All activity measures had returned to baseline by 3 months. Wrist‐worn accelerometery is acceptable to patients and feasible as a surrogate measure for monitoring postoperative recovery from day‐case surgery. Our results suggest that patients may overestimate their rate of recovery from day‐case surgery, which has important implications for future research.
The process of angiogenesis has been well documented, but little is known about the biology of lymphatic endothelial cells and the molecular mechanisms controlling lymphangiogenesis. The homeobox ...gene Prox1 is expressed in a subpopulation of endothelial cells that, after budding from veins, gives rise to the mammalian lymphatic system. In Prox1−/− embryos, this budding becomes arrested at around embryonic day (E)11.5, resulting in embryos without lymphatic vasculature. Unlike the endothelial cells that bud off in E11.5 wild‐type embryos, those of Prox1‐null embryos did not co‐express any lymphatic markers such as VEGFR‐3, LYVE‐1 or SLC. Instead, the mutant cells appeared to have a blood vascular phenotype, as determined by their expression of laminin and CD34. These results suggest that Prox1 activity is required for both maintenance of the budding of the venous endothelial cells and differentiation toward the lymphatic phenotype. On the basis of our findings, we propose that a blood vascular phenotype is the default fate of budding embryonic venous endothelial cells; upon expression of Prox1, these budding cells adopt a lymphatic vasculature phenotype.
Lymphatic vessels are essential for immune surveillance, tissue fluid homeostasis and fat absorption. Defects in lymphatic vessel formation or function cause lymphedema. Here we show that the ...vascular endothelial growth factor C (VEGF-C) is required for the initial steps in lymphatic development. In Vegfc-/- mice, endothelial cells commit to the lymphatic lineage but do not sprout to form lymph vessels. Sprouting was rescued by VEGF-C and VEGF-D but not by VEGF, indicating VEGF receptor 3 specificity. The lack of lymphatic vessels resulted in prenatal death due to fluid accumulation in tissues, and Vegfc+/- mice developed cutaneous lymphatic hypoplasia and lymphedema. Our results indicate that VEGF-C is the paracrine factor essential for lymphangiogenesis, and show that both Vegfc alleles are required for normal lymphatic development.
There is some evidence for a bidirectional association between obesity and depression. However, studies examining weight change and depression are scarce and report inconsistent findings.
The ...objective was to investigate the relationship between average annual percentage weight change and depression in mid-aged women.
This was a prospective cohort study.
A total of 8246 women aged 45-50 years at baseline participating in the Australian Longitudinal Study on Women's Health were surveyed every 3 years over a 12-year period. Information on body mass index and depression was collected at each survey. We used regression models to investigate the effect of weight change predicting depression and vice versa, by calculating odds ratios (ORs) with 95% confidence intervals (CIs).
Weight gain was associated with an increased risk of prevalence (OR 1.39, 95% CI 1.25-1.56) and incidence (OR 1.30, 95% CI 1.14-1.49) of depression. However, in time-lagged analyses, where weight change between the two preceding surveys was used to predict incidence of depression at the current survey, no statistically significant associations with depression were found. Compared with women without depression, women with prevalent and incident depression had an increased risk of weight gain (OR 1.29, 95% CI 1.19-1.40 and OR 1.20, 95% CI 1.05-1.38, respectively). When incidence of depression was lagged with respect to weight change between the two subsequent surveys, depression remained associated with an increased risk (OR 1.19, 95% CI 1.00-1.41) of gaining weight.
These findings suggest that depression may cause weight gain over the next 3 years, but that weight change (loss or gain) may not lead to depression. Further research at shorter intervals, perhaps 6 monthly or yearly is needed to ascertain whether weight change is an independent predictor of depression in the shorter term.
The many recent discoveries concerning the molecular biologic bases of malformations of cortical development and the discovery of new such malformations have rendered previous classifications out of ...date. A revised classification of malformations of cortical development is proposed, based on the stage of development (cell proliferation, neuronal migration, cortical organization) at which cortical development was first affected. The categories have been created based on known developmental steps, known pathologic features, known genetics (when possible), and, when necessary, neuroimaging features. In many cases, the precise developmental and genetic features are uncertain, so classification was made based on known relationships among the genetics, pathologic features, and neuroimaging features. A major change since the prior classification has been the elimination of the separation between diffuse and focal/multifocal malformations, based on the recognition that the processes involved in these processes are not fundamentally different; the difference may merely reflect mosaicism, X inactivation, the influence of modifying genes, or suboptimal imaging. Another change is the listing of fewer specific disorders to reduce the need for revisions; more detail is added in other smaller tables that list specific malformations and malformation syndromes. This classification is useful to the practicing physician in that its framework allows a better conceptual understanding of the disorders, while the component of neuroimaging characteristics allows it to be applied to all patients without necessitating brain biopsy, as in pathology-based classifications.
We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and ...wave events and to explore the timing of activity in these regions.
Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs.
Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity.
In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.
The coconut rhinoceros beetle (CRB: Oryctes rhinoceros Linnaeus) is one of the most damaging pests to coconut and oil palms in Asia and the Pacific Islands. Adults bore into the crown and damage ...developing fronds, which affects tree development and yield. The insect is native to South and Southeast Asia and was inadvertently introduced into the Pacific in 1909. It has since spread to several Pacific island nations and territories, causing significant economic impact on these important coconut and palm-growing regions. In the 1950s and 1960s, an international biological control effort was initiated to search for and release natural enemy species. Release of the Oryctes rhinoceros nudivirus Huger (OrNV) and the species complex of Metarhizium Sorokin (Hypocreales: Clavicipitaceae) was successful in controlling CRB in its invaded range. Recently a new biotype of the beetle, known as CRB-G, has spread into the Pacific Islands causing unprecedented levels of damage due to the failure of previously successful biological control agents (BCAs) to suppress this biotype. The re-emergence of CRB as a serious pest warrants a rigorous re-evaluation of potential BCAs and a new search for effective natural enemies if necessary. In this article, we review literature on CRB to 1) analyze past introductions of BCAs and their effectiveness; 2) identify potentially important natural enemies and their geographical origins; and 3) assess possible approaches for utilization of BCAs against the new wave of CRB invasion. Research gaps and directions deserving future attention are highlighted and a strategy for renovation of biological controls for CRB suggested.
Recent and historical deposition of mercury (Hg) was examined over a broad geographic area from southwestern Northwest Territories to Labrador and from the U.S. Northeast to northern Ellesmere Island ...using dated sediment cores from 50 lakes (18 in midlatitudes (41−50°N), 14 subarctic (51−64°N) and 18 in the Arctic (65−83°N)). Distinct increases of Hg over time were observed in 76% of Arctic, 86% of subarctic and 100% of midlatitude cores. Subsurface maxima in Hg depositional fluxes (μg m−2 y−1) were observed in only 28% of midlatitude lakes and 18% of arctic lakes, indicating little recent reduction of inputs. Anthropogenic Hg fluxes adjusted for sediment focusing and changes in sedimentation rates (ΔF adj,F ) ranged from −22.9 to 61 μg m−2 y−1 and were negatively correlated (r = −0.57, P < 0.001) with latitude. Hg flux ratios (FRs; post-1990)/pre-1850) ranged from 0.5 to 7.7. The latitudinal trend for Hg ΔF adj,F values showed excellent agreement with predictions of the global mercury model, GRAHM for the geographic location of each lake (r = 0.933, P < 0.001). The results are consistent with a scenario of slow atmospheric oxidation of mercury, and slow deposition of reactive mercury emissions, declining with increasing latitude away from emission sources in the midlatitudes, and support the view that there are significant anthropogenic Hg inputs in the Arctic.
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