Femoral neck fracture during physical therapy following surface replacement arthroplasty: a preventable complication? A case report

This case report describes two cases of peri-prosthetic fracture during physical therapy in patients who underwent a hip resurfacing, or surface replacement arthroplasty. The fractures occurred with forceful passive combined flexion and external rotation. Functional results were ultimately obtained in both cases, requiring conversion to total hip arthroplasty. Recognizing patient risk factors and cautioning therapists about the possibility of fracture may have prevented these complications

Postnatal PPARδ Activation and Myostatin Inhibition Exert Distinct yet Complimentary Effects on the Metabolic Profile of Obese Insulin-Resistant Mice

BACKGROUND: Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice. METHODOLOGY/PRINCIPAL FINDINGS: Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. CONCLUSIONS/SIGNIFICANCE: The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

A Universal Mathematical Model for a New Combined-Cycle

ABSTRACT A Universal Mathematical Model (UMM) has been developed and applied to a combined-cycle, fossil-fuel power system. The UMM includes static and dynamic models of the system. The static model allows for thermodynamic and thermochemical analyses of the basic system components (reformer, turbine, membrane separator, fuel cell, air compressor, heat exchanger, and other components) and the entire system. The dynamic model provides for mode-to-mode (a partial load to a full or nominal load) time determination for the individual system components and for the entire system. System transient modes were studied, and it was determined that the reforming reactor transition time should be no less than 200 sec, which results in a system mode-tomode transition time of three to four minutes

A Universal Mathematical Model for a New Combined-Cycle

ABSTRACT A universal mathematical model (UMM) has been developed and applied to the LAJ (for Labinov, Armstrong, and Judkins) cycle, a new combined-cycle, fossil-fuel power system. The UMM includes static and dynamic models of the system. The static model allows for thermodynamic and thermochemical analyses of the basic system components (reformer, turbine, membrane separator, fuel cell, air compressor, heat exchanger, and other components) and the entire system. Equilibrium compositions of reforming products are defined by minimizing Gibbs free energy of the mixtures using the Lagrangian multiplier method. The dependence of the main system parameters on pressure (P), temperature (T), and water-to -methane molar ratios (N) at the steam reformer have been evaluated. For selected reforming parameters, viz., P = 4.0 MPa and T = 1200 K, the degree of methane conversion is near 95% with N = 5. However, in view of mass and size limitations on equipment, a lower value of N = 3 is preferred, in which case the degree of methane conversion is 88%. The dependence of the system static model parameters on N has been investigated, and economic characteristics of the model have been evaluated for an output power of 250 kW. It is shown that when, N = 3, the fuel cost contribution to overall electricity costs is 1 cent/kWh. INTRODUCTION A combined-cycle, fossil -fuel power plant is a complex system composed of a considerable number of components. The system operation efficiency depends not only on the efficiency of each component but also on optimal integration and interaction of components. These optimal characteristics must be maintained when the system passes from operation under a nominal load to operation under a partial load. Therefore, mode-to-mode time must meet the user's demands. A mathematical simulation mode

The Relationship among Hypoxia, Proliferation, and Outcome in Patients with De Novo Glioblastoma: A Pilot Study1

The hypoxia and proliferation index increase with grade in human glial tumors, but there is no agreement whether either has prognostic importance in glioblastomas. We evaluated these end points individually and together in 16 de novo human glioblastomas using antibodies against the 2-nitroimidazole hypoxia detection agent EF5 and the proliferation detection agent Ki-67. Frozen tumor tissue sections were fluorescence-stained for nuclei (Hoechst 33342), hypoxia (anti-EF5 antibodies), and proliferation (anti-Ki-67 antibodies). EF5 binding adjacent to Ki-67+ cells, overall EF5 binding, the ratio of these values, and the proliferation index were evaluated. Patients were classified using recursive partitioning analysis and followed up until recurrence and/or death. Recursive partitioning analysis was statistically significant for survival (P = .0026). Overall EF5 binding, EF5 binding near Ki-67+ cells, and proliferation index did not predict recurrence. Two additional survival analyses based on ratios of the overall EF5 binding to EF5 binding near Ki-67+ cells were performed. High and low ratio values were determined by two cutoff points: (a) the 50% value for the ratio [EF5/Ki-67Binding]/[Tumorbinding] = RatioEF5 50% and (b) the median EF5 value (75.6%) of the ratio [EF5/Ki-67Binding]/[Tumorbinding] = Ratiopatients median. On the basis of the RatioEF5 50%, recurrence (P = .0074) and survival (P = .0196) could be predicted. Using the Ratiopatients median, only survival could be predicted (P = .0291). In summary, patients had a worse prognosis if the [EF5/Ki-67Binding]/[Tumorbinding] ratio was high. A hypothesis for the mechanisms and translational significance of these findings is discussed