TASK DEFINITION: Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: A severe complication in the replacement therapy of hemophilia A (HA) patients is the development of alloantibodies (inhibitors) against factor VIII, which neutralizes the substituted factor. The primary genetic risk factors influencing the development of inhibitors are F8 gene mutations. Interleukins and cytokines that are involved in the regulation of B-lymphocyte development are other possible targets as genetic risk factors. This study assesses the possible involvement of 9 selected single nucleotide gene polymorphisms (SNPs) with interleukins (IL-4, IL-5, and IL-10), transforming growth factor beta 1 (TGF-1), and interferon gamma (IFN-) in inhibitor development in severely affected HA patients carrying a null mutation in the F8 gene.', 'A total of 173 HA patients were screened for intron 22 inversion and null mutations (nonsense and deletions). Genotyping of a total of 9 SNPs in genes IL-4, IL-5, IL-10, TGF-1, and IFN- in 103 patients and 100 healthy individuals was carried out.', 'An association analysis between 42 inhibitor (+) and 61 inhibitor (-) patients showed a significant association with the T allele of rs2069812 in the IL-5 gene promoter and patients with inhibitors (p=0.0251). The TT genotype was also significantly associated with this group with a p-value of 0.0082, odds ratio of about 7, and confidence interval of over 90%, suggesting that it is the recessive susceptibility allele and that the C allele is the dominant protective allele.

SOLUTION: Is a Polymorphism in the IL-5 Gene Associated with Inhibitor Development in Severe Hemophilia A Patients?

PROBLEM: Large concentrations of meperidine inhibit N-methyl-D-aspartate-(NMDA) receptor channels by channel block mechanisms. Extracellular pH regulates the activity and drug sensitivity of NMDA-receptor channels. We examined the influence of extracellular pH on sensitivity to meperidine of epsilon/zeta heteromeric NMDA-receptor channels expressed in Xenopus oocytes. Inhibition of epsilon1/zeta1, epsilon2/zeta1, epsilon3/zeta1, and epsilon4/zeta1 channels by meperidine was dependent on pH, with more inhibition at acidic pH and less inhibition at alkaline pH. The degree of voltage-dependence of meperidine block was only slightly affected by changes in pH, whereas affinity for meperidine was greatly reduced at alkaline pH. Furthermore, interaction of meperidine with Mg(2+) block was reduced at alkaline pH. Because the percentage of the protonated form of meperidine is only slightly affected by pH, changes in properties of the meperidine binding site may be involved in mechanisms of alteration of meperidine potency by pH.

SOLUTION: Is n-methyl-D-aspartate receptor channel block by meperidine dependent on extracellular pH?

PROBLEM: An in vitro cadaveric study comparing cage-vertebra interface strengths for 3 different screw-cement configurations.', 'To determine the effects of cement augmentation of pedicle screws on cage-vertebra interface failure properties for 2 interbody device shapes (elliptical or cloverleaf); and to compare between pedicle and anterior vertebral body screws with cement augmentation.', 'Pedicle or anterior screw fixation is commonly used with interbody device fixation. Cement has recently been shown to augment screw fixation in the osteoporotic spine by improving the screw-bone interface strength. The effect of cement augmentation of pedicle or anterior screws on cage-vertebra interface properties has not been previously studied or compared.', 'An elliptical or a cloverleaf-shaped indentor covering 40% of the endplate was axially compressed against the superior endplate of 48 thoracolumbar vertebrae. Each vertebra had polymethylmethacrylate cement augmentation of 1) anterior screws, 2) pedicle screws, or 3) pedicle screws without cement. Compressive load was applied through a mechanism that allowed unconstrained rotation of the indentors.', 'Cement augmentation of pedicle screws resulted in significantly higher failure loads (54%) and failure strength (69%) for both shaped indentors when compared with uncemented pedicle screws. There was no significant difference in failure load and failure strength between pedicle and anterior screws with cement augmentation. Indentor shape was not a significant factor on failure load or failure strength.

SOLUTION:
Does cement augmentation of vertebral screws enhance the interface strength between interbody device and vertebral body?