Stearoyl-coenzyme A desaturase 1 (SCD1) catalyzes the rate-limiting step of de novo lipogenesis and modulates lipid homeostasis. Although numerous SCD1 inhibitors were tested for treating metabolic disorders both in preclinical and clinic studies, the tissue-specific roles of SCD1 in modulating obesity-associated metabolic disorders and determining the pharmacological effect of chemical SCD1 inhibition remain unclear. Here a novel role for intestinal SCD1 in obesity-associated metabolic disorders was uncovered. Intestinal SCD1 was found to be induced during obesity progression both in humans and mice. Intestine-specific, but not liver-specific, SCD1 deficiency reduced obesity and hepatic steatosis. A939572, an SCD1-specific inhibitor, ameliorated obesity and hepatic steatosis dependent on intestinal, but not hepatic, SCD1. Mechanistically, intestinal SCD1 deficiency impeded obesity-induced oxidative stress through its novel function of inducing metallothionein 1 in intestinal epithelial cells. These results suggest that intestinal SCD1 could be a viable target that underlies the pharmacological effect of chemical SCD1 inhibition in the treatment of obesity-associated metabolic disorders.

This cohort study was undertaken over 54 months to observe the effectiveness of primary surgery and long-term oral methotrexate (MXT) treatment on lower lip squamous cell carcinoma (SCC) in Milne Bay Province and National Capital District, Papua New Guinea (PNG). The current standard treatment for lower lip SCC depends on the stage of the disease: stage 1 is treated with either surgery or radiotherapy only, while stages 2 and 3 are treated with surgery followed by chemotherapy and radiotherapy; stage 4 is metastatic disease and is treated with palliative chemotherapy and radiotherapy. Due to limited treatment options available in Papua New Guinea for cancer patients, this study was conducted with the primary aim of finding an alternative, affordable and effective treatment option for lower lip SCC in our setting. There were 20 patients recruited in the study with histologically confirmed SCC of the lower lip. They had primary surgeries which included selective neck dissection (SND) for positive neck involvement (stages 2, 3 and 4) (8; 40%) and tumour resection and reconstruction (20; 100%), and, once the wounds had healed well, they were commenced on long-term oral MXT treatment for 24 months. The follow-up period was approximately 54 months and the results of the primary outcomes measured were: no local recurrence, no neck metastasis, no distant metastasis and no mortality. In conclusion, even though we acknowledge the small number of subjects recruited, this cohort study does give some hope to health care practitioners, including surgeons, in PNG that lower lip SCC can be alternatively treated with surgery and methotrexate when there are no other treatment modalities available in their health facility.

Hirschsprung's disease (HD) is a disease entity synonymous with infants and newborns. We present a case of HD in a 21-year-old female that was never diagnosed in her infancy. This case highlights the diagnosis of HD in adults and enlightens us that this congenital disease may rarely be diagnosed in adults.