Complete genome sequences of Streptomyces griseus phages Spelly and Phredrick.

We present the complete genome sequences of two viruses with siphovirus morphology, isolated from soils collected in Southwestern Indiana using the host Streptomyces griseus. Spelly is a BE2 cluster phage with a 131,347-bp genome. Phredrick is a BK1 cluster phage with a 128,873-bp genome.

Development of a Virtual Pharmacy Resident Conference.

A virtual conference for pharmacists and residents offered a cost-effective means to share research findings across facilities.

Modulation of gamma-secretase reduces beta-amyloid deposition in a transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized pathologically by the abundance of senile plaques and neurofibrillary tangles in the brain. We synthesized over 1200 novel gamma-secretase modulator (GSM) compounds that reduced Abeta(42) levels without inhibiting epsilon-site cleavage of APP and Notch, the generation of the APP and Notch intracellular domains, respectively. These compounds also reduced Abeta(40) levels while concomitantly elevating levels of Abeta(38) and Abeta(37). Immobilization of a potent GSM onto an agarose matrix quantitatively recovered Pen-2 and to a lesser degree PS-1 NTFs from cellular extracts. Moreover, oral administration (once daily) of another potent GSM to Tg 2576 transgenic AD mice displayed dose-responsive lowering of plasma and brain Abeta(42); chronic daily administration led to significant reductions in both diffuse and neuritic plaques. These effects were observed in the absence of Notch-related changes (e.g., intestinal proliferation of goblet cells), which are commonly associated with repeated exposure to functional gamma-secretase inhibitors (GSIs).

Early weight bearing after complete tibial shaft fractures in children.

This study determined the prevalence of complications related to early weight bearing and the factors associated with time to healing in children after a complete tibial shaft fracture. Radiographs and medical records were reviewed from patients with unilateral, closed, complete tibial shaft fractures who were treated nonoperatively with a long leg cast. There were 55 males (68.8%) and 25 females (31.2%) with a mean ± SD age of 6.0 ± 4.0 years (range 1-16). There were few complications (2.5%) and patients healed faster if they bore weight earlier (0.3 days faster for each day earlier to weight bearing, P = 0.02), were younger (2.3 days faster per year younger, P < 0.001), were female (2.7 days faster than males, P = 0.02), or did not have a closed reduction (3.8 days faster, P = 0.002) (R = 0.63). Time to weight bearing after complete tibial shaft fracture was not associated with an increased risk of complications. Earlier weight bearing was associated with a shorter time to healing. This study provides support for treatment with early weight bearing in children with closed, complete tibial shaft fractures.

Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection.

The emergence of H5N1 avian influenza and the threat of new or adapted viruses in bioterrorism have created an urgent interest in identifying agents to enhance the immune response to primary virus infection. Active hexose correlated compound (AHCC) is a natural mushroom extract reported to increase natural killer (NK) cell activity, survival, and bacterial clearance in young mice. However, the effects of AHCC on the response to viral infections have not been studied. In this study, young C57BL/6 mice were supplemented with 1 g AHCC/(kg body weight x d) for 1 wk prior to and throughout infection with influenza A (H1N1, PR8). Supplementation increased survival, decreased the severity of infection, and shortened recovery time following intranasal infection with flu, as determined by the recovery of body weight and epithelial integrity in the lungs. AHCC increased NK activity in lungs at d 1 (P < 0.05) and d 4 (P < 0.01) and in the spleen at d 2 postinfection (P < 0.01). Supplementation increased the percentage (P < 0.05) and number (P < 0.01) of NK1.1+ cells in the lung and reduced the infiltration of lymphocytes and macrophages compared with controls (P < 0.01). These data suggest that AHCC supplementation boosts NK activity, improves survival, and reduces the severity of influenza infection in young mice. Bolstering innate immunity with dietary bioactives may be one avenue for improving the immune response to primary flu infection.

Direct current stimulation for spine fusion in a nicotine exposure model.

BACKGROUND CONTEXT: Decreased effectiveness in spinal fusion procedures in patients who smoke before, during, or after the operation has been noted in several clinical studies. In previous work, direct current (DC) electrical stimulation has been shown to enhance inter-transverse process fusion in a rabbit model. PURPOSE: To test the efficacy of DC stimulation on bone healing in spinal fusion in rabbits exposed to nicotine. STUDY DESIGN/SETTING: A randomized and controlled interventional study. METHODS: Thirty male New Zealand white rabbits received a single level posterolateral, inter-transverse process fusion with autologous iliac crest bone. One group (control) acted as a control without nicotine or electrical stimulation. A second group (Nic) received a continuous dose of nicotine via a transdermal patch to simulate a heavy smoker, and a third group, nicotine/stimulator group (Nic/Stim), additionally received a 100-microamp DC stimulator. The fusion masses (L5-L6) and the adjacent unfused control segment (L4-L5) were evaluated radiographically, manually, and biomechanically. RESULTS: The Nic group showed significantly higher fusion rate compared with the control group. The Nic/Stim group also demonstrated significantly higher fusion rate and X-ray trabeculation compared with the control group. However, the Nic/Stim group was not significantly higher than the Nic group in fusion rate or X-ray trabeculation. CONCLUSIONS: Nicotine significantly improved fusion rate compared with controls, and DC stimulation significantly increased X-ray trabeculation of nicotine treated rabbits compared with controls.

Correlation between serum alanine aminotransferase activity and age: an inverted U curve pattern.

BACKGROUND: Alanine aminotransferase (ALT) activity is the most widely used laboratory test for the recognition of liver disease. Normality limits for values of serum ALT activity have been questioned lately. One reason for this recent uncertainty may be an unrecognized decline in aminotransferase levels in the aging population. AIMS: Cross-sectional evaluation of the association between age and ALT activity. METHODS: Laboratory data of residents in single home for the aged and of adult subjects in three general practice clinics in Jerusalem, Israel were reviewed, excluding subjects with known liver disease. A single laboratory performed all the tests. We examined the associations of serum aminotransferase levels with age, sex, body-mass-index (BMI), and estimated glomerular filtration rate (GFR). Polynomial regression and analysis of variance (ANOVA) with corrections for multiple comparisons were utilized for the statistical analyses. RESULTS: One hundred and twenty-eight individuals from the home for the aged and 207 individuals from three family practices were included. ALT activity linearly regressed with age (r = 0.22, p < 0.0001). However, polynomial regression revealed a better fit (r = 0.33, p < 0.0001), creating an inverted U curve with a peak at 40-55 yr. According to age groups, serum ALT level was 19 +/- 13 U/L in those under 40 yr, 25 +/- 19 U/L in 40-55 yr olds, 22 +/- 10 U/L in 56-72 yr olds, 17 +/- 9 U/L in 73-83 yr olds, and 13 +/- 5 U/L in 83-100 yr olds (p < 0.0001). GFR (r = 0.1, p < 0.05) and BMI (r = 0.14, p < 0.01) weakly correlated with ALT. Gender also associated with ALT; 22 +/- 15 U/L in men, and 17 +/- 11 U/L in women (p < 0.005). Multiple regression analysis including age, gender, GFR, and BMI revealed that age (p= 0.01) and gender (p= 0.04) retained association with ALT activity. No such associations were noted for aspartate aminotransferase (AST) activity. CONCLUSIONS: Our data suggest a significant association between age and serum ALT activity. This association is not a simple linear correlation, but rather an inverted-U-like relation. Thus, when interpreting the laboratory results of a subject suspected of liver disease, age should probably be taken into account. Larger-scale studies are needed to better characterize this issue.