Quantitative retinal vascular perfusion density mapping agreed closely with grading based on clinical features and may offer an objective method for monitoring disease progression in diabetic retinopathy.

The fetal and neonatal immune systems are uniquely poised to generate tolerance to self, maternal and environmental antigens encountered in the womb and shortly after birth. However, the tolerogenic nature of fetal and neonatal immunity can be detrimental in the context of pathogens, leading to overwhelming bacterial infections or chronic viral infections. A variety of mechanisms contribute to fetal and neonatal tolerance, including a propensity to generate Foxp3 + regulatory T cells (Treg cells). However, the mechanism(s) of fetal Foxp3 + T-cell differentiation, the specific antigen-presenting cells required and factors that inhibit Treg generation after the neonatal period are poorly understood. Here, we demonstrate that a subset of CD14 + monocytes expressing the scavenger molecule, CD36, can generate CD4 + and CD8 + T cells that coexpress Foxp3 and Tbet from both umbilical cord blood. These Foxp3 + T-bet + T cells potently suppress T-cell proliferation and ameliorate xenogeneic graft-versus-host disease. CD14 + CD36 + monocytes provide known Treg-inducing signals: membrane-bound transforming growth factor-beta and retinoic acid. Unexpectedly, adult peripheral blood monocytes are also capable of inducing Foxp3 + T cells from both cord blood and adult peripheral na€ ıve T cells. The induction of Foxp3 + T cells in umbilical cord blood by monocytes was inhibited by the lymphoid fraction of adult peripheral blood cells. These studies highlight a novel immunoregulatory role of monocytes and suggest that antigen presentation by CD36 hi monocytes may contribute to the peripheral development of Foxp3 + T-bet + T cells with regulatory functions in both neonates and adults.

Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single‐blinded randomized cross‐over protocols, blood glucose levels, plasma concentrations of insulin, C‐peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor‐heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0–2.5 mA, 30 min) or sham‐taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects ( n = 16) were fasted throughout the protocol and in a second protocol, subjects ( n = 10) received a high‐calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham‐taVNS. No significant effects of taVNS on heart rate variability and baroreceptor‐heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: −115.5 ± 28.3 pg/ml vs. sham‐taVNS: −51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow‐up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.

SummarySouth-East Asia’s bird trade is of global conservation concern as it has massively depleted wild populations of many species. Parrots (Order Psittaciformes) are especially vulnerable because they are the most heavily traded group of birds globally under the Convention on International Trade in Endangered Species (CITES) appendices. Singapore’s involvement in the global pet bird trade as a transhipment hub is well documented, particularly for parrots. Yet, much less is known about the links between its domestic and international trade. We attempt to quantify this relationship by comparing bird trade data on the CITES database with past market surveys of pet shops, complemented with semi-structured interviews with 30 parrot owners in Singapore. We report a decline in total imports and exports of CITES-listed birds in Singapore from 2005 to 2016, consistent with global trends after the European Union trade ban on wild bird imports. However, parrots continue to make up the majority of total imports; and there was a yearly increase in the percentage of parrot imports out of total imports. In addition, we report a difference in imports and exports of 54,207 CITES I, II and III listed birds into Singapore i.e. birds imported but not re-exported. A substantial proportion of these birds were possibly channelled into the domestic pet trade or used as breeding stock. Interviews with parrot owners confirmed the growing demand and popularity of parrots and particularly of larger species. We conclude that the domestic demand for parrots may have been previously underestimated, and make recommendations to manage Singapore’s international and domestic pet bird trade such as implementing a licensing and records system to track the movement of birds.

Background: Some patients with diabetic macular edema (DME) fail to completely respond to anti-vascular endothelial growth factor (VEGF) therapy. These patients have a high treatment burden in the absence of significant improvement. We investigate the role of intravitreal dexamethasone insert (IDI) in eyes with super-refractory DME. Methods: A non-randomized interventional study was performed among eyes with super-refractory DME refractory to anti-VEGF therapy. Eyes were treated with IDI after failing clinical response to anti-VEGF, with a minimum of 15 prior. Failure to respond was defined as failure of vision to improve at least one line on Snellen Acuity chart, central subfield thickness (CST) greater than 320 μm, or failure of CST to improve by 10% or more. Eyes with glaucoma or prior uncontrolled steroid-responsive ocular hypertension were excluded. Patient outcomes were analyzed at weeks 6, 12, 24, and year 1. Results: Six eyes of four patients were identified. All patients had failed aflibercept. The mean number of prior anti-VEGF injections was 34.5. Eyes received an average of 2.92 dexamethasone injections per person-year (PY) and required breakthrough anti-VEGF injection at 1.95/PY. Mean pre-treatment visual acuity was 0.475 LogMAR, improving to 0.342 at week 6, and 0.375 at 1 year. Mean CST pre-injection was 386.5 mm, improving to 315 mm at 1 year. No glaucoma developed. Conclusions: Intravitreal dexamethasone insert appears effective in eyes with super-refractory DME. IDI resulted in excellent anatomic improvement on SD-OCT as well as modest visual improvement. Injection burden was reduced in those who may otherwise receive years of monthly treatments.