The Na/K-ATPase α1/Src interaction regulates metabolic reserve and Western diet intolerance.

AIM: Highly prevalent diseases such as insulin resistance and heart failure are characterized by reduced metabolic flexibility and reserve. We tested whether Na/K-ATPase (NKA)-mediated regulation of Src kinase, which requires two NKA sequences specific to the α1 isoform, is a regulator of metabolic capacity that can be targeted pharmacologically. METHODS: Metabolic capacity was challenged functionally by Seahorse metabolic flux analyses and glucose deprivation in LLC-PK1-derived cells expressing Src binding rat NKA α1, non-Src-binding rat NKA α2 (the most abundant NKA isoform in the skeletal muscle), and Src binding gain-of-function mutant rat NKA α2. Mice with skeletal muscle-specific ablation of NKA α1 (skα1-/-) were generated using a MyoD:Cre-Lox approach and were subjected to treadmill testing and Western diet. C57/Bl6 mice were subjected to Western diet with or without pharmacological inhibition of NKA α1/Src modulation by treatment with pNaKtide, a cell-permeable peptide designed by mapping one of the sites of NKA α1/Src interaction. RESULTS: Metabolic studies in mutant cell lines revealed that the Src binding regions of NKA α1 are required to maintain metabolic reserve and flexibility. Skα1-/- mice had decreased exercise endurance and mitochondrial Complex I dysfunction. However, skα1-/- mice were resistant to Western diet-induced insulin resistance and glucose intolerance, a protection phenocopied by pharmacological inhibition of NKA α1-mediated Src regulation with pNaKtide. CONCLUSIONS: These results suggest that NKA α1/Src regulatory function may be targeted in metabolic diseases. Because Src regulatory capability by NKA α1 is exclusive to endotherms, it may link the aerobic scope hypothesis of endothermy evolution to metabolic dysfunction.

Patients with pelvic fractures from blunt trauma. What is the cause of mortality and when?

BACKGROUND: Mortality in patients sustaining pelvic fractures has been reported to be 4% to 15%. We sought to investigate the cause of death based on timing and evaluate if type of fracture and Injury Severity Score have an influence on the survival time. METHODS: Sixty-nine patients of eight hundred sixty seven with a pelvic fracture who died during their hospital admission were included. Fractures were classified using the Arbeitsgemeinschaft Osteosynthesefragen/Orthopaedic Trauma Association system. Cause determined by autopsy in 48/69. RESULTS: The leading cause of death within 6 hours was abdominal and pelvic hemorrhage; 6 to 24 hours head injury, and greater than 24 hours multiple organ dysfunction syndrome. Survival time did not correlate between fracture type (P < .12) or Injury Severity Score. Only 2 patients died of isolated pelvic hemorrhage. CONCLUSIONS: Despite the advances made in acute management of the traumatized patient in the emergency department, mortality is unavoidable in a small group of patients with hemorrhage being the commonest cause of early death but isolated pelvic hemorrhage rare.

The impact of buccal corridors on smile attractiveness.

The aim of this study was to assess the impact of various sized buccal corridors (BCs) on smile attractiveness. One female smiling photograph, displaying first molar to first molar (M1-M1), was digitally altered to produce (1) smiles that filled 84, 88, 92, 96, and 100 per cent of the oral aperture; (2) second premolar to second premolar smiles (PM2-PM2) that filled 84, 88, 92, and 96 per cent of the oral aperture; and (3) smiles with asymmetrical BC that filled 88, 90, 94, and 96 per cent of the oral aperture. The 18 smiles produced were evaluated by 82 orthodontists (70 males and 12 females) and 94 laypeople (40 males and 54 females). Paired t-tests were used to evaluate differences within the orthodontist and laypeople groups: independent t-tests were used to compare the two groups. The effect of age and gender on the ratings was evaluated by two-way analysis of variance. Orthodontists and laypeople rated smiles with small BCs as significantly (P < 0.05) more attractive than those with large BCs. Orthodontists rated M1-M1 smiles as more attractive than PM2-PM2 smiles, whereas laypeople preferred PM2-PM2 smiles. Orthodontists rated only two of eight asymmetrical smiles as less attractive than would be expected for symmetrical smiles with similar arch widths; laypeople did not rate any asymmetrical smiles as less attractive than would be expected. Rater age and gender did not significantly influence the impact of BCs on smile attractiveness.