Endurance running has evolved over the course of millions of years and it is now one of the most popular sports today. However, the risk of stress injury in distance runners is high because of the repetitive ground impact forces exerted. These injuries are not only detrimental to the runner, but also place a burden on the medical community. Preventative measures are essential to decrease the risk of injury within the sport. Common running injuries include patellofemoral pain syndrome, tibial stress fractures, plantar fasciitis, and Achilles tendonitis. Barefoot running, as opposed to shod running (with shoes), has recently received significant attention in both the media and the market place for the potential to promote the healing process, increase performance, and decrease injury rates. However, there is controversy over the use of barefoot running to decrease the overall risk of injury secondary to individual differences in lower extremity alignment, gait patterns, and running biomechanics. While barefoot running may benefit certain types of individuals, differences in running stance and individual biomechanics may actually increase injury risk when transitioning to barefoot running. The purpose of this article is to review the currently available clinical evidence on barefoot running and its effectiveness for preventing injury in the runner. Based on a review of current literature, barefoot running is not a substantiated preventative running measure to reduce injury rates in runners. However, barefoot running utility should be assessed on an athlete-specific basis to determine whether barefoot running will be beneficial.

The yeast amphiphysin homologue Rvs167p plays a role in regulation of the actin cytoskeleton, endocytosis, and sporulation. Rvs167p is a phosphoprotein in vegetatively growing cells and shows increased phosphorylation upon treatment with mating pheromone. Previous work has shown that Rvs167p can be phosphorylated in vitro by the cyclin-dependent kinase Pho85p complexed with its cyclin Pcl2p. Using chymotryptic phosphopeptide mapping, we have identified the sites on which Rvs167p is phosphorylated in vitro by Pcl2p-Pho85p. We have shown that these same sites are phosphorylated in vivo during vegetative growth and that phosphorylation at two of these sites is Pcl-Pho85p dependent. In cells treated with mating pheromone, the MAP kinase Fus3p is needed for full phosphorylation of Rvs167p. Functional genomics and genetics experiments revealed that mutation of other actin cytoskeleton genes compromises growth of a strain in which phosphorylation of Rvs167p is blocked by mutation. Phosphorylation of Rvs167p inhibits its interaction in vitro with Las17p, an activator of the Arp2/3 complex, as well as with a novel protein, Ymr192p. Our results suggest that phosphorylation of Rvs167p by a cyclin-dependent kinase and by a MAP kinase is an important mechanism for regulating protein complexes involved in actin cytoskeleton function.

A mutant allele (pol3-L612M) of the DNA polymerase ␦ gene in Saccharomyces cerevisiae that confers sensitivity to the antiviral drug phosphonoacetic acid (PAA) was constructed. We report that PAA-sensitivity tagging DNA polymerases is a useful method for selectively and reversibly inhibiting one type of DNA polymerase. Our initial studies reveal that replication by the L612M-DNA pol ␦ requires Rad27 flap endonuclease activity since the pol3-L612M strain is not viable in the absence of RAD27 function. The L612M-DNA pol ␦ also strongly depends on mismatch repair (MMR). Reduced viability is observed in the absence of any of the core MMR proteins-Msh2, Mlh1, or Pms1-and severe sensitivity to PAA is observed in the absence of the core proteins Msh6 or Exo1, but not Msh3. We propose that pol3-L612M cells need the Rad27 flap endonuclease and MMR complexes composed of Msh2/Msh6, Mlh1/Pms1, and Exo1 for correct processing of Okazaki fragments. E UKARYOTIC DNA polymerase ␦ (DNA pol ␦) is reacid (foscarnet) are effective antiviral drugs that inhibit replication by herpes and vaccinia DNA polymerases quired for chromosome replication, recombination, and repair, but there are several other DNA polymerases (Mao et al. 1975;Ö berg 1989;Taddie and Traktman 1991) and the HIV reverse transcriptase (Larder et al. in the cell, which makes it difficult to study DNA pol ␦ specifically. DNA polymerase inhibitors have the poten-1987). PAA appears to act as a pyrophosphate analog in the polymerase active center of sensitive DNA polytial to be useful, but the currently available inhibitors merases to severely reduce the polymerization reaction are not specific. Aphidicolin, for example, inhibits all (Leinbach et al. 1976). Thus, since yeast like other euthree replicative DNA polymerases, DNA pols ␣, ␦, and karyotes is relatively resistant to PAA, PAA sensitivity is ε (Burgers and Bauer 1988). Mutations that confer expected to increase substantially if the wild-type DNA temperature sensitivity (ts) provide a way to block replipol ␦ is converted to a PAA-sensitive mutant. cation by a selected DNA polymerase, but ts DNA pol ␦ To construct a yeast DNA pol ␦ mutant with PAA sensimutants lose viability rapidly after exposure to the restrictivity, we used mutational studies of the bacteriophage T4 tive temperature (Weinert and Hartwell 1993), which DNA polymerase as a guide (Reha-Krantz 1995). The prevents studies of recovery mechanisms. We report a bacteriophage T4 DNA polymerase, like eukaryotic DNA new method for inhibiting DNA pol ␦ selectively: we pols ␣, ␦, and ε, is relatively resistant to PAA; however, constructed a mutant DNA pol ␦ in Saccaromyces cerevisiae several mutant T4 DNA polymerases were identified that is inhibited by the antiviral drug phosphonoacetic with markedly increased sensitivity (Reha-Krantz et al. acid (PAA).1993; Reha-Krantz and Nonay 1994). T4 DNA poly-PAA was chosen as a new DNA pol ␦ inhibitor primarmerase and eukaryotic DNA pol ␦ are members of a ily for two reasons. First, PAA does not need to be prol...

In vitro gamma interferon release assays (IGRAs) are increasingly used as an alternative to the traditional tuberculin skin test for the diagnosis of latent Mycobacterium tuberculosis infection. Evaluation of the Quanti-FERON-TB Gold in-tube assay (QFT-IT) prior to large-scale implementation at the Stanford Hospital and Clinics for a health care worker screening program revealed a critical preanalytical factor affecting the results. We found that incubation delay significantly increased the frequency of indeterminate results. In this study, QFT-IT was performed with samples from healthy volunteers, and replicate tubes were incubated at 37°C either immediately or after a delay at room temperature for 6 and 12 h. No indeterminate results (0/41) were seen when the assay was performed with immediate incubation. Incubation delays of 6 and 12 h yielded indeterminate results at rates of 10% (2/20) (P ‫؍‬ 0.10) and 17.1% (7/41) (P ‫؍‬ 0.01), respectively. The increased rate of indeterminate results was due to a decrease in the mean values for the mitogen-nil tubes when incubation was delayed for 6 h (P ‫؍‬ 0.004) and 12 h (P < 0.001). The rates of concordance of positive or negative results obtained following immediate incubation and following 6-and 12-h delays were 77.8% (14/18) and 79.4% (27/34), respectively. Subsequent implementation of the immediate incubation procedure in our screening program for 14,830 health care workers yielded an indeterminate result rate of 0.36% over a period of 12 months, a significant improvement over the reported rates of 5 to 40% for QFT-IT. We conclude that immediate incubation of QFT-IT tubes is an effective way to minimize indeterminate results. The effect of incubation delay on the accuracy of QFT-IT remains to be determined.