Loss of mitochondrial pyruvate carrier 1 supports proline-dependent proliferation and collagen biosynthesis in ovarian cancer.

The pyruvate transporter MPC1 (mitochondrial pyruvate carrier 1) acts as a tumour-suppressor, loss of which correlates with a pro-tumorigenic phenotype and poor survival in several tumour types. In high-grade serous ovarian cancers (HGSOC), patients display copy number loss of MPC1 in around 78% of cases and reduced MPC1 mRNA expression. To explore the metabolic effect of reduced expression, we demonstrate that depleting MPC1 in HGSOC cell lines drives expression of key proline biosynthetic genes; PYCR1, PYCR2 and PYCR3, and biosynthesis of proline. We show that altered proline metabolism underpins cancer cell proliferation, reactive oxygen species (ROS) production, and type I and type VI collagen formation in ovarian cancer cells. Furthermore, exploring The Cancer Genome Atlas, we discovered the PYCR3 isozyme to be highly expressed in a third of HGSOC patients, which was associated with more aggressive disease and diagnosis at a younger age. Taken together, our study highlights that targeting proline metabolism is a potential therapeutic avenue for the treatment of HGSOC.

Neurodevelopmental Therapy for Cerebral Palsy: A Meta-analysis.

BACKGROUND AND OBJECTIVE: Bobath therapy, or neurodevelopmental therapy (NDT) is widely practiced despite evidence other interventions are more effective in cerebral palsy (CP). The objective is to determine the efficacy of NDT in children and infants with CP or high risk of CP. METHODS: Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Embase, and Medline were searched through March 2021. Randomized controlled trials comparing NDT with any or no intervention were included. Meta-analysis was conducted with standardized mean differences calculated. Quality was assessed by using Cochrane Risk of Bias tool-2 and certainty by using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Of 667 records screened, 34 studies (in 35 publications, 1332 participants) met inclusion. Four meta-analyses were conducted assessing motor function. We found no effect between NDT and control (pooled effect size 0.13 [-0.20 to 0.46]), a moderate effect favoring activity-based approaches (0.76 [0.12 to 1.40]) and body function and structures (0.77 [0.19 to 1.35]) over NDT and no effect between higher- and lower-dose NDT (0.32 [-0.11 to 0.75]). A strong recommendation against the use of NDT at any dose was made. Studies were not all Consolidated Standards of Reporting Trials-compliant. NDT versus activity-based comparator had considerable heterogeneity (I2 = 80%) reflecting varied measures. CONCLUSIONS: We found that activity-based and body structure and function interventions are more effective than NDT for improving motor function, NDT is no more effective than control, and higher-dose NDT is not more effective than lower-dose. Deimplementation of NDT in CP is required.

Rehabilitation Evidence-Based Decision-Making: The READ Model.

Evidence-based practice is the foundation of rehabilitation for maximizing client outcomes. However, an unacceptably high number of ineffective or outdated interventions are still implemented, leading to sub-optimal outcomes for clients. This paper proposes the Rehabilitation Evidence bAsed Decision-Making (READ) Model, a decision-making algorithm for evidence-based decision-making in rehabilitation settings. The READ Model outlines a step-by-step layered process for healthcare professionals to collaboratively set goals, and to select appropriate interventions. The READ Model acknowledges the important multi-layered contributions of client's preferences and values, family supports available, and external environmental factors such as funding, availability of services and access. Healthcare professionals can apply the READ Model to choose interventions that are evidence-based, with an appropriate mode, dose, and with regular review, in order to achieve client's goals. Two case studies are used to demonstrate application of the READ Model: cerebral palsy and autism spectrum disorder. The READ Model applies the four central principles of evidence-based practice and can be applied across multiple rehabilitation settings.

State of the Evidence Traffic Lights 2019: Systematic Review of Interventions for Preventing and Treating Children with Cerebral Palsy.

PURPOSE OF REVIEW: Cerebral palsy is the most common physical disability of childhood, but the rate is falling, and severity is lessening. We conducted a systematic overview of best available evidence (2012-2019), appraising evidence using GRADE and the Evidence Alert Traffic Light System and then aggregated the new findings with our previous 2013 findings. This article summarizes the best available evidence interventions for preventing and managing cerebral palsy in 2019. RECENT FINDINGS: Effective prevention strategies include antenatal corticosteroids, magnesium sulfate, caffeine, and neonatal hypothermia. Effective allied health interventions include acceptance and commitment therapy, action observations, bimanual training, casting, constraint-induced movement therapy, environmental enrichment, fitness training, goal-directed training, hippotherapy, home programs, literacy interventions, mobility training, oral sensorimotor, oral sensorimotor plus electrical stimulation, pressure care, stepping stones triple P, strength training, task-specific training, treadmill training, partial body weight support treadmill training, and weight-bearing. Effective medical and surgical interventions include anti-convulsants, bisphosphonates, botulinum toxin, botulinum toxin plus occupational therapy, botulinum toxin plus casting, diazepam, dentistry, hip surveillance, intrathecal baclofen, scoliosis correction, selective dorsal rhizotomy, and umbilical cord blood cell therapy. We have provided guidance about what works and what does not to inform decision-making, and highlighted areas for more research.

What has change management in industry got to do with improving patient safety?

BACKGROUND: Healthcare is often in a constant state of change - for political, technological, patient related, and scientific reasons. Yet, for a business where change is the norm, too little time is spent thinking theoretically about how change occurs. One area where change is still needed is in patient safety. METHODS: Presented is an analysis of the literature on change to suggest how this may inform patient safety. RESULTS: No one change approach guarantees success in patient safety. Success very much depends on selecting the best fit change framework and adapting it to local context. Well regarded change models, like that of Kotter, are not well tested within a healthcare context. Those that are, such as Pettigrew, do not specifically address all the issues associated with patient safety. Kotter's phases of change may be applied in a healthcare context to enhance patient safety. CONCLUSION: Kotter's model is well studied in non-healthcare contexts and has potential to be adapted for improving patient safety.