Fully biodegradable amphiphilic thermoresponsive star block copolymers featuring 4 and 6 arms are reported for micellar delivery of doxorubicin.

Prior work established that exercise alleviates muscle function loss in a clinically relevant rodent model mimicking the clinical sequelae of severely burned patients. On the basis of these data, we posit that pharmacologic treatment with insulin combined with exercise further mitigates loss of muscle function following severe burn with immobilization. Twenty‐four Sprague–Dawley rats were assessed and trained to complete a climbing exercise. All rats followed a standardized protocol to mimic severe burn patients (40% total body surface area scald burn); all rats were immediately placed into a hindlimb unloading apparatus to simulate bedrest. The rats were then randomly assigned to four treatment groups: saline vehicle injection without exercise (VEH/NEX), insulin (5 U/kg) injection without exercise (INS/NEX), saline vehicle with daily exercise (VEH/EX), and insulin with daily exercise (INS/EX). The animals were assessed for 14 days following injury. The groups were compared for multiple variables. Isometric tetanic (Po) and twitch (Pt) forces were significantly elevated in the plantaris and soleus muscles of the INS/EX rats ( P < 0.05). Genomic analysis revealed mechanistic causes with specific candidate changes. Molecular analysis of INS/EX rats revealed Akt phosphorylated by PDPK1 was increased with this treatment, and it further activated downstream signals mTOR, eEF2, and GSK3‐ β ( P < 0.05). Furthermore, muscle RING‐finger protein‐1 (MuRF‐1), an E3 ubiquitin ligase, was reduced in the INS/EX group ( P < 0.05). Insulin and resistance exercise have a positive combined effect on the muscle function recovery in this clinically relevant rodent model of severe burn. Both treatments altered signaling pathways of increasing protein synthesis and decreasing protein degradation.

Background & Aims Characterization of relative adrenal insufficiency (RAI) in cirrhosis is heterogeneous with regard to studied patient populations and diagnostic methodology. We aimed to describe the prevalence and prognostic importance of RAI in non‐critically ill patients with cirrhosis. Methods A systematic review and meta‐analysis was performed using MeSH terms and Boolean operators to search five large databases (Ovid‐MEDLINE, ScienceDirect, Web of Science, Cochrane Library and http://clinicaltrials.gov). The population of interest was patients with cirrhosis and without critical illness. The primary outcome was the pooled prevalence of RAI as defined by a peak total cortisol level <18 μg/dl, delta total cortisol <9 μg/dl or composite of the two thresholds in response either a standard‐dose or low‐dose short synacthen test. Odds ratios and standardized mean differences from random‐effects models estimated important clinical outcomes and patient characteristics by adrenal functional status. Results Twenty‐two studies were included in final analysis, comprising 1991 patients with cirrhosis. The pooled prevalence of RAI was 37% (95% CI 33–42%). The prevalence of RAI varied by Child–Pugh classification, type of stimulation test used, specific diagnostic threshold and by severity of illness. Ninety‐day mortality was significantly higher in patients with RAI (OR 2.88, 95% CI 1.69–4.92, I2 = 15%, p < 0.001). Conclusions Relative adrenal insufficiency is highly prevalent in non‐critically ill patients with cirrhosis and associated with increased mortality. Despite the proposed multifactorial pathogenesis, no studies to date have investigated therapeutic interventions in this specific population.