Disruption of hmgA by DNA Duplication is Responsible for Hyperpigmentation in a Vibrio anguillarum Strain.

Vibrio anguillarum 531A, isolated from a diseased fish in the Atlantic Ocean, is a mixture composed of about 95 and 5% of highly pigmented cells (strain 531Ad) and cells with normal levels of pigmentation (strain 531Ac), respectively. Analysis of the V. anguillarum 531Ad DNA region encompassing genes involved in the tyrosine metabolism showed a 410-bp duplication within the hmgA gene that results in a frameshift and early termination of translation of the homogentisate 1,2-dioxygenase. We hypothesized that this mutation results in accumulation of homogentisate that is oxidized and polymerized to produce pyomelanin. Introduction in E. coli of recombinant clones carrying the V. anguillarum hppD (4-hydroxyphenylpyruvate-dioxygenase), and a mutated hmgA produced brown colored colonies. Complementation with a recombinant clone harboring hmgA restored the original color to the colonies confirming that in the absence of homogentisate 1,2-dioxygenase the intermediary in tyrosine catabolism homogentisate accumulates and undergoes nonenzymatic oxidation and polymerization resulting in high amounts of the brown pigment. Whole-genome sequence analysis showed that V. anguillarum 531 Ac and 531Ad differ in the hmgA gene mutation and 23 mutations, most of which locate to intergenic regions and insertion sequences.

Osteoporosis: A Review of Treatment Options.

Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.

The Culture of Patient Safety Practice: Systematic Review.

INTRODUCTION: Regulations and guidelines are essential components of maintaining safety in multiple industries. In health care these processes exist to help distinguish weaknesses in patient care and identify adverse events. We review the processes that have been established in health care to promote the culture of patient safety. METHODS: Sources were acquired through the NCBI (National Center for Biotechnology Information) database using the keywords "safety," "World Health Organization" and "Joint Commission on Accreditation of Healthcare Organizations." Other sources were obtained through research into specific safety processing topics of industrial and nonindustrial institutions. RESULTS: The organizational properties of patient care expand beyond the number of incidents an institution experiences and include standardized safety values for specific patient care procedures. Tools such as SBAR (Situation, Background, Assessment, Recommendation), Reason's Swiss cheese model and the general guidelines established by the WHO have been used to detect and reduce the likelihood of errors in patient practice. These tools also demonstrate the importance of adopting regulated checklists and protocols that are essential at every stage of patient care. CONCLUSIONS: While various systems have been implemented throughout the health care industry to overcome processing weaknesses, a continued display of effectiveness and improvement of current subspecialty specific guidelines are necessary for the assurance of safety in contemporary patient care.