A new cryptic host defense peptide identified in human 11-hydroxysteroid dehydrogenase-1 ß-like: from in silico identification to experimental evidence.

BACKGROUND: Host defence peptides (HDPs) are evolutionarily conserved components of innate immunity. Human HDPs, produced by a variety of immune cells of hematopoietic and epithelial origin, are generally grouped into two families: beta structured defensins and variably-structured cathelicidins. We report the characterization of a very promising cryptic human HDP, here called GVF27, identified in 11-hydroxysteroid dehydrogenase-1 ß-like protein. METHODS: Conformational analysis of GVF27 and its propensity to bind endotoxins were performed by NMR, Circular Dichroism, Fluorescence and Dynamic Light Scattering experiments. Crystal violet and WST-1 assays, ATP leakage measurement and colony counting procedures were used to investigate antimicrobial, anti-biofilm, cytotoxicity and hemolytic activities. Anti-inflammatory properties were evaluated by ELISA. RESULTS: GVF27 possesses significant antibacterial properties on planktonic cells and sessile bacteria forming biofilm, as well as promising dose dependent abilities to inhibit attachment or eradicate existing mature biofilm. It is unstructured in aqueous buffer, whereas it tends to assume a helical conformation in mimic membrane environments as well as it is able to bind lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Notably it is not toxic towards human and murine cell lines and triggers a significant innate immune response by attenuating expression levels of pro-inflammatory interleukins and release of nitric oxide in LPS induced macrophages. CONCLUSION: Human GVF27 may offer significant advantages as leads for the design of human-specific therapeutics. GENERAL SIGNIFICANCE: Human cryptic host defence peptides are naturally no immunogenic and for this they are a real alternative for solving the lack of effective antibiotics to control bacterial infections.

Obesity-related hospitalization costs to the U.S. Navy, 1993 to 1998.

The objective of this work was to estimate the cost to the U.S. Navy for obesity-related hospital admissions by examining (1) inpatient utilization associated with obesity; (2) the rank order, probability, and total facility costs of obesity-related diagnosis-related groups (DRGs); and (3) expected inpatient expenses. The frequency and probability of inpatient events in the Navy's active duty population were derived from the Department of Defense's Retrospective Case Mix Analysis System. Medicare-based facility costs per DRG were estimated. These measures were combined in a decision-analytic model. Expected facility costs per obesity-related admission for active duty Navy personnel increased by age group from $3,328 for 18 to 24 year olds to $5,746 for 45 to 64 year olds. The annual avoidable inpatient cost for the Navy was estimated to be $5,842,627 for the top 10 obesity-related DRGs. Improvements to the Navy Physical Readiness Program and other interventions that may reduce obesity, obesity-related health care use, and the public economic burden should be pursued.

The impact of a shipboard weight control program.

OBJECTIVE: The specific aim was to determine whether a multifaceted approach to weight loss and physical readiness could be implemented onboard a deployed combatant ship of the U.S. Navy. RESEARCH METHODS AND PROCEDURES: Thirty-nine men (31+/-6 years old, mean+/-standard deviation) assigned to the USS ENTERPRISE (CVN 65) during a 6-month Mediterranean deployment who had failed their previous Physical Readiness Test due to excessive body weight (108+/-11 kg overweight) were randomly assigned to nutrition, cognitive-behavioral obesity treatment plus exercise or to the Navy's usual treatment (control), which is exercise alone. RESULTS: Outcomes for the treatment group were significantly better than the controls, with 8.6+/-5.0 vs. 5.0+/-4.1 kg weight loss, 8% vs. 5% reduction in original body weight, and body fat loss of 7% vs. 5%. Triglycerides declined significantly greater in the treatment group than the controls (145 mg/dL to 109 mg/dL vs. 146 mg/dL to 145 mg/dL, p<0.05), whereas depression and eating behaviors significantly improved among treated men. Problematic environmental factors were the limited variety of heart healthy foods in the galley, short meal breaks, and long mess hall lines that led to eating snacks from vending machines and frequent port calls. DISCUSSION: Although greater weight loss than would be expected of a Navy usual care group diluted the treatment effect, the treated men still fared significantly better. The physical readiness implication of this research has the potential to impact Navy health promotion programs and policy, the health and well-being of its personnel, and the Navy's ability to meet mission requirements.