Signal transducer and activator of transcription (STAT) 1 and STAT3 are expressed in the human ovary and have Janus kinase 1-independent functions in the COV434 human granulosa cell line.

Ovarian granulosa cells are fundamental for oocyte maintenance and maturation. Recent studies have demonstrated the importance of members of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signalling pathway in the granulosa cell population of mouse and horse ovaries, with perturbation of JAK1 signalling in the mouse shown to impair oocyte maintenance and accelerate primordial follicle activation. The presence and role of the JAK/STAT pathway in human granulosa cells has yet to be elucidated. In this study, expression of JAK1, STAT1 and STAT3 was detected in oocytes and granulosa cells of human ovarian sections from fetal (40 weeks gestation) and premenopausal ovaries (34-41 years of age; n=3). To determine the effects of JAK1 signalling in granulosa cells, the human granulosa-like cell line COV434 was used, with JAK1 inhibition using ruxolitinib. Chemical inhibition of JAK1 in COV434 cells with 100nM ruxolitinib for 72h resulted in significant increases in STAT3 mRNA (P=0.034) and p-Y701-STAT1 protein (P=0.0117), demonstrating a role for JAK1 in modulating STAT in granulosa cells. This study implicates a conserved role for JAK/STAT signalling in human ovary development, warranting further investigation of this pathway in human granulosa cell function.

Long-term change in respiratory function following spinal cord injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To model the effect of time since injury on longitudinal respiratory function measures in spinal cord injured-individuals and to investigate the effect of patient characteristics. SETTING: A total of 173 people who sustained a spinal cord injury between 1966 and April 2013 and who had previously participated in research or who underwent clinically indicated outpatient respiratory function tests at the Austin Hospital in Melbourne, Australia, were included in the study. At least two measurements over time were available for analysis in 59 patients. METHODS: Longitudinal data analysis was performed using generalised linear regression models to determine changes in respiratory function following spinal cord injury from immediately post injury to many years later. Secondly, we explored whether injury severity, age, gender and body mass index (BMI) at injury altered the time-dependent change in respiratory function. RESULTS: The generalised linear regression model showed no significant change (P=0.276) in respiratory function measured in (forced) vital capacity ((F)VC) after the spinal cord injury. However, significant (P<0.05) differences in respiratory function over time were found when categorising age and BMI. CONCLUSION: This clinical cohort with long-term, repeated measurements of respiratory function showed no significant overall change in respiratory function over 23 years. However, a decline in respiratory function over time was observed in subgroups of individuals older than 30 years at the onset of injury and in those with a BMI>30 kg m(-2).

Validation of the Dutch clinical prediction rule for ambulation outcomes in an inpatient setting following traumatic spinal cord injury.

STUDY DESIGN: Retrospective study. OBJECTIVES: To determine the accuracy of a previously described Dutch clinical prediction rule for ambulation outcome in routine clinical practice. SETTING: Adult (⩾18 years) patients who were admitted to the Austin Hospital with a traumatic spinal cord injury between January 2006 and August 2014. METHODS: Data from medical records were extracted to determine the score of the Dutch clinical ambulation prediction rule proposed by van Middendorp et al. in 2011. A receiver-operating characteristics (ROC) curve was generated to investigate the performance of the prediction rule. Univariate analyses were performed to investigate which factors significantly influence ambulation after a traumatic spinal cord injury. RESULTS: The area under the ROC curve (AUC) obtained during the current study (0.939, 95% confidence interval (CI) (0.892, 0.986)) was not significantly different from the AUC from the original Dutch clinical prediction model (0.956, 95% CI (0.936, 0.976)). Factors that were found to have a significant influence on ambulation outcome were time spent in the ICU, number of days hospitalised and injury severity. Age at injury initially showed a significant influence on ambulation however, this effect was not apparent after inclusion of the 24 patients who died due to the trauma (and therefore did not walk after their injuries). CONCLUSION: The Dutch ambulation prediction rule performed similarly in routine clinical practice as in the original, controlled study environment in which it was developed. The potential effect of survival bias in the original model requires further investigation.