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Introduction: Melatonin has been suggested an adjunctive therapy in neonatal encephalopathy (NE). Melatonin reduces oxidative stress and neutrophil activation; however, the immunological effects in NE have not been studied. Methods: Infants with NE and neonatal controls were prospectively recruited. Whole blood was sampled in the first week of life. Following endotoxin and or melatonin treatment, diurnal variation was measured by RT PCR for circadian rhythm genes (brain and Muscle Arnt-Like protein [BMAL1], circadian locomotor output cycles kaput [CLOCK], Nuclear Receptor Subfamily 1 Group D Member 2 [REV Erβ], and cryptochrome circadian clock [CRY]). Neutrophil and monocyte cell surface markers of activation CD11b, reactive oxygen intermediates (ROIs), and Toll-like receptor (TLR)-4 were also examined by flow cytometry in matching samples. Results: Serum and RNA samples from forty infants were included (controls n = 20; NE n = 20) over the first week of life. Melatonin reduced neutrophil CD11b and TLR-4 expression in response to LPS in infants with NE compared to controls. There were no differences in ROIs. BMAL1 and CLOCK baseline gene expression levels were similar. BMAL1 was significantly decreased with LPS stimulation in NE. There was no significant diurnal variation in melatonin, neutrophil, and monocyte function or circadian genes. Conclusions: Melatonin alters immune function ex vivo in infants with NE. Infants with NE have altered immune circadian responses following LPS stimulation, which have potential for modulation. [ABSTRACT FROM AUTHOR]

The case follows the journey of Irish social enterprise FoodCloud as it rises to the extensive task of reducing global food waste by providing an environmentally-sensitive, sociallyresponsible, and economically-viable alternative. From its humble beginnings as a socially oriented technology start-up pioneered by Aoibheann O'Brien and Iseult Ward, FoodCloud has utilised both its innovative technology platform and an innate ability to form successful partnerships as the strategy to pave its international expansion. The case illustrates the sizable challenges in leading on social enterprise initiatives. The organization's development path is described to provide a good sense of the growth trajectory that emerged for FoodCloud during its young history to date. Notably, FoodCloud have developed strategic capabilities that are arguably, critical to the survival and success of any social enterprise entity. [ABSTRACT FROM AUTHOR]