Postpartum Seizure and Subarachnoid Haemorrhage Secondary to Moyamoya Disease.

Postpartum seizures secondary to subarachnoid haemorrhage (SAH) are rare. The incidence of pregnancy-related SAH is increasing and is highest during the delivery and postpartum periods. While there have been cases in the literature of SAH occurring postpartum, very few are associated with Moyamoya disease. We present a rare case of a young woman diagnosed with Moyamoya disease following immediate postpartum seizures secondary to a SAH. She was medically managed and discharged without any neurological deficits. This case highlights how seizures and SAH may develop in the immediate postpartum period in an otherwise healthy young woman.

Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice.

BCL-2 proteins are known to engage each other to determine the fate of a cell after a death stimulus. However, their evolutionary conservation and the many other reported binding partners suggest an additional function not directly linked to apoptosis regulation. To identify such a function, we studied mice lacking the BH3-only protein BIM. BIM-/- cells had a higher mitochondrial oxygen consumption rate that was associated with higher mitochondrial complex IV activity. The consequences of increased oxygen consumption in BIM-/- mice were significantly lower body weights, reduced adiposity and lower hepatic lipid content. Consistent with reduced adiposity, BIM-/- mice had lower fasting blood glucose, improved insulin sensitivity and hepatic insulin signalling. Lipid oxidation was increased in BIM-/- mice, suggesting a mechanism for their metabolic phenotype. Our data suggest a role for BIM in regulating mitochondrial bioenergetics and metabolism and support the idea that regulation of metabolism and cell death are connected.

Polycystic ovarian syndrome: Prevalence and impact on the wellbeing of Australian women aged 16-29 years.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is the most common condition among reproductive-aged women. However, its exact prevalence is unknown. AIMS: To determine the prevalence of PCOS in Australian women aged 16-29 years using the National Institutes of Health (NIH) criteria compared to self-reported PCOS, to compare co-morbidities between the groups and to determine the most distressing aspect of a diagnosis of PCOS for these young women. MATERIALS AND METHODS: Participants were recruited from the Young Female Health Initiative (YFHI) and Safe-D studies. Participants completed questionnaires, physical examinations and blood tests from 2012 to 2016. In March 2016, two supplementary questionnaires were distributed: the first, comprising questions on reproductive health and impact of diagnosis, was sent to participants who self-reported having PCOS in the original studies. The second, comprising general reproductive health questions, was sent to the remainder. RESULTS: The prevalence of PCOS, according to the NIH criteria, was 12% (31/254), while the prevalence of self-reported PCOS was 8% (23/300). Only 35% (8/23) of those with self-reported PCOS actually fulfilled the NIH criteria for PCOS. Comorbidities were relatively similar among groups. Finally, approximately 65% (15/23) were unhappy or worried about their initial PCOS diagnosis, with 72% (13/18) stating fertility concerns were the most distressing aspect of their diagnosis. CONCLUSIONS: The lack of consistent and accurate diagnosis of PCOS in young women potentially leads to over-diagnosis. This creates unnecessary fears of health complications, particularly infertility. Therefore, we recommend the development of standardised criteria with set parameters that allow for better diagnosis of PCOS.

Lipotoxic Stress Induces Pancreatic ß-Cell Apoptosis through Modulation of Bcl-2 Proteins by the Ubiquitin-Proteasome System.

Pancreatic ß-cell loss induced by saturated free fatty acids (FFAs) is believed to contribute to type 2 diabetes. Previous studies have shown induction of endoplasmic reticulum (ER) stress, increased ubiquitinated proteins, and deregulation of the Bcl-2 family in the pancreas of type 2 diabetic patients. However, the precise mechanism of ß-cell death remains unknown. In the present study we demonstrate that the FFA palmitate blocks the ubiquitin-proteasome system (UPS) and causes apoptosis through induction of ER stress and deregulation of Bcl-2 proteins. We found that palmitate and the proteasome inhibitor MG132 induced ER stress in ß-cells, resulting in decreased expression of the prosurvival proteins Bcl-2, Mcl-1, and Bcl-XL, and upregulation of the prodeath BH3-only protein PUMA. On the other hand, pharmacological activation of the UPS by sulforaphane ameliorated ER stress, upregulated prosurvival Bcl-2 proteins, and protected ß-cells from FFA-induced cell death. Furthermore, transgenic overexpression of Bcl-2 protected islets from FFA-induced cell death in vitro and improved glucose-induced insulin secretion in vivo. Together our results suggest that targeting the UPS and Bcl-2 protein expression may be a valuable strategy to prevent ß-cell demise in type 2 diabetes.

A mutant p53/let-7i-axis-regulated gene network drives cell migration, invasion and metastasis.

Most p53 mutations in human cancers are missense mutations resulting in a full-length mutant p53 protein. Besides losing tumor suppressor activity, some hotspot p53 mutants gain oncogenic functions. This effect is mediated in part, through gene expression changes due to inhibition of p63 and p73 by mutant p53 at their target gene promoters. Here, we report that the tumor suppressor microRNA let-7i is downregulated by mutant p53 in multiple cell lines expressing endogenous mutant p53. In breast cancer patients, significantly decreased let-7i levels were associated with missense mutations in p53. Chromatin immunoprecipitation and promoter luciferase assays established let-7i as a transcriptional target of mutant p53 through p63. Introduction of let-7i to mutant p53 cells significantly inhibited migration, invasion and metastasis by repressing a network of oncogenes including E2F5, LIN28B, MYC and NRAS. Our findings demonstrate that repression of let-7i expression by mutant p53 has a key role in enhancing migration, invasion and metastasis.