Cost-benefit of stockpiling drugs for influenza pandemic

We analyzed strategies for the use of stockpiled antiviral drugs in the context of a future influenza pandemic and estimated cost-benefit ratios. Current stockpiling of oseltamivir appears to be cost-saving to the economy under several treatment strategies, including therapeutic treatment of patients and postexposure prophylactic treatment of patients' close contacts.     

Mutations in the fourth β‐propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers

Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani‐Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly. LRP4 inhibits LRP6/LRP5‐mediated activation of canonical Wnt signaling and mediates sclerostin‐dependent inhibition of bone formation. p.D1403H and p.Q1564K are located within the fourth β‐propeller of the extracellular protein domain that has yet to be associated with human disease. Functional analyses of p.D1403H and p.Q1564K show that they significantly decrease LRP4's inhibition of Wnt signaling. These results suggest that variants in the fourth β‐propeller of the extracellular protein domain may cause a phenotype distinct from previously characterized LRP4 variants.     

Clinical and Epidemiological Significance of Carbapenem Resistance in Acinetobacter baumannii Infections

Carbapenems are considered the treatment of choice for Acinetobacter baumannii infections. Many facilities implement preventive measures toward only carbapenem-resistant A. baumannii (CRAB). However, the independent role of the carbapenem resistance determinant on patient outcomes remains controversial. In a 6-year analysis of adults with A. baumannii bloodstream infection (BSI), the outcomes of 149 CRAB isolates were compared to those of 91 patients with carbapenem-susceptible A. baumannii. In bivariable analyses, CRAB BSIs were significantly associated with worse outcomes and with a delay in the initiation of appropriate antimicrobial therapy (DAAT). However, in multivariable analyses, carbapenem resistance status was no longer associated with poor outcomes, while DAAT remained an independent predictor. The epidemiological significance of A. baumannii should not be determined by its resistance to carbapenems.     

Minimally invasive colorectal resection is associated with a rapid and sustained decrease in plasma levels of epidermal growth factor (EGF) in the colon cancer setting

Background  

Epidermal growth factor (EGF) stimulates tumor growth directly via tumor cell EGF receptors or indirectly via its proangiogenic effects. This study’s purpose was to determine the impact of minimally invasive colorectal resection (MICR) on postoperative (postop) plasma EGF levels in the colorectal cancer (CRC) and benign disease settings and to see if preoperative (PreOp) EGF levels are altered in cancer patients.     

Varying environments can speed up evolution

Simulations of biological evolution, in which computers are used to evolve systems toward a goal, often require many generations to achieve even simple goals. It is therefore of interest to look for generic ways, compatible with natural conditions, in which evolution in simulations can be speeded. Here, we study the impact of temporally varying goals on the speed of evolution, defined as the number of generations needed for an initially random population to achieve a given goal. Using computer simulations, we find that evolution toward goals that change over time can, in certain cases, dramatically speed up evolution compared with evolution toward a fixed goal. The highest speedup is found under modularly varying goals, in which goals change over time such that each new goal shares some of the subproblems with the previous goal. The speedup increases with the complexity of the goal: the harder the problem, the larger the speedup. Modularly varying goals seem to push populations away from local fitness maxima, and guide them toward evolvable and modular solutions. This study suggests that varying environments might significantly contribute to the speed of natural evolution. In addition, it suggests a way to accelerate optimization algorithms and improve evolutionary approaches in engineering.     

Molecular targets for tendon neoformation

Tendons and ligaments are unique forms of connective tissue that are considered an integral part of the musculoskeletal system. The ultimate function of tendon is to connect muscles to bones and to conduct the forces generated by muscle contraction into movements of the joints, whereas ligaments connect bone to bone and provide joint stabilization. Unfortunately, the almost acellular and collagen I-rich structure of tendons and ligaments makes them very poorly regenerating tissues. Injured tendons and ligaments are considered a major clinical challenge in orthopedic and sports medicine. This Review discusses the several factors that might serve as molecular targets that upon activation can enhance or lead to tendon neoformation.     

Light intensity mediated polarotaxis in Pontella karachiensis (Pontellidae, Copepoda)

Polarization sensitivity provides animals with information not available in the intensity or spectral domains. We examined the polarotaxis reactions in the epiplanktonic copepod Pontella karachiensis. Polarotaxis reactions were intensity dependent. At intensities corresponding to ambient daylight, P. karachiensis showed an attraction to a polarized light field; while at low intensities, corresponding to nighttime illumination, it showed negative polarotaxis. P. karachiensis’s eye contained two classes of photoreceptors, each class with microvilli at orthogonal orientation to the other. P. karachiensis’ eye structure can provide information regarding the polarization percentage but is not sufficient to calculate the exact e-vector orientation. The threshold for polarotoxisis response was 20-30%. Animals responded similarly to horizontal and vertical polarization; and also showed negative phototaxis, affected by light polarization. Results suggest that P. karachiensis responds to polarized light analogously to changes in brightness. The dynamic pattern of polarotaxis responses suggests that polarization sensitivity may enable P. karachiensis to detect other planktonic animals.     

Oxytrex Minimizes Physical Dependence While Providing Effective Analgesia: A Randomized Controlled Trial in Low Back Pain

Physical dependence or withdrawal is an expected effect of prolonged opioid therapy. Oxytrex (oxycodone + ultralow-dose naltrexone) is an investigational drug shown here to minimize physical dependence while providing strong analgesia with twice-daily dosing. In this 719-patient, double-blind, placebo- and active-controlled Phase III clinical trial in chronic low back pain, patients were randomized to receive placebo, oxycodone qid, or oxytrex qid or bid. Each oxytrex tablet contains 1 microg naltrexone; oxytrex bid and qid treatments provide 2 and 4 microg naltrexone/day, respectively. Following a washout, patients with pain >or=5 on a 0-10 scale were dose-escalated weekly from 10 up to 80 mg/day until reaching adequate pain relief (相似文献