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Joseph V Pergolizzi Jr,1 Robert B Raffa,2,3 Marco Pappagallo,4 Charles Fleischer,1 Joseph Pergolizzi III,1 Gianpietro Zampogna,5 Elizabeth Duval,1 Janan Hishmeh,1 Jo Ann LeQuang,1 Robert Taylor Jr1 1NEMA Research, Inc., Naples, FL, 2University of Arizona College of Pharmacy, University of Arizona, Tucson, AZ, 3Temple University School of Pharmacy, Temple University, Philadelphia, PA, 4Department of Medicine, Albert Einstein College of Medicine, New York, NY, 5Department of Medicine, St. Luke’s Hospital, Cleveland, OH, USA Abstract: Opioid-induced constipation (OIC), a prevalent and distressing side effect of opioid therapy, does not reliably respond to treatment with conventional laxatives. OIC can be a treatment-limiting adverse event. Recent advances in medications with peripherally acting μ-opioid receptor antagonists, such as methylnaltrexone, naloxegol, and alvimopan, hold promise for treating OIC and thus extending the benefits of opioid analgesia to more chronic pain patients. Peripherally acting μ-opioid receptor antagonists have been clinically tested to improve bowel symptoms without compromise to pain relief, although there are associated side effects, including abdominal pain. Other treatment options include fixed-dose combination products of oxycodone analgesic together with naloxone. Keywords: opioid-induced constipation, opioid bowel disorder, PAMORA, peripherally acting mu-opioid receptor antagonist, noncancer pain patients, opioid-associated side effects

Joseph V Pergolizzi Jr,1 Robert B Raffa,2,3 Charles Fleischer,1 Gianpietro Zampogna,1 Robert Taylor Jr1 1NEMA Research, Naples, FL, 2University of Arizona College of Pharmacy, Tucson, AZ, 3Temple University School of Pharmacy, Philadelphia, PA, USA Abstract: With a global prevalence of ~9%–12%, low back pain (LBP) is a serious public health issue, associated with high costs for treatment and lost productivity. Chronic LBP (cLBP) involves central sensitization, a neuropathic pain component, and may induce maladaptive coping strategies and depression. Treating cLBP is challenging, and current treatment options are not fully satisfactory. A new BioErodible MucoAdhesive (BEMA®) delivery system for buprenorphine has been developed to treat cLBP. The buccal buprenorphine (BBUP) film developed for this product (Belbuca™) allows for rapid delivery and titration over a greater range of doses than was previously available with transdermal buprenorphine systems. In clinical studies, BBUP was shown to effectively reduce pain associated with cLBP at 12 weeks with good tolerability. The most frequently reported side effects with the use of BBUP were nausea, constipation, and vomiting. There was no significant effect on the QT interval vs placebo. Chronic pain patients using other opioids can be successfully rotated to BBUP without risk of withdrawal symptoms or inadequate analgesia. The role of BBUP in managing cLBP remains to be determined, but it appears to be a promising new product in the analgesic arsenal in general. Keywords: buccal, transmucosal, buprenorphine, chronic low back pain, BEMA, drug delivery Belbuca

This study investigated the use of the transactional leadership style (TLB) by restaurant managers and its effect on food safety compliance by restaurant employees in the United States. Utilizing parallel mediation analyses, the study investigated the impact that fear, responsibility, knowledge, and gain had on compliance. Results provide theoretical and practical implications related to the effective use of TLB in motivating compliance amongst employees. The importance of implementing disciplinary actions for noncompliance is suggested and results indicate that compliance was more likely when employees felt a sense of responsibility, understood food safety rules, and believed they would experience gain. [ABSTRACT FROM AUTHOR]

A pharmacokinetic dosing study with camphor was used to determine whether selection lines of high-juniper-consuming goats (HJC, n = 12) and low-juniper-consuming goats (LJC, n = 12) differed in their respective disposition kinetics. Postdosing plasma camphor concentrations were used to examine whether a timed single blood sample collected after intraruminal administration of camphor would be a useful screening test to aid in the identification of HJC. Yearling female Boer x Spanish goats (n = 24) received a single intraruminal dose of monoterpene cocktail (0.270 g/ kg of BW) containing 4 different monoterpenes that represented their composition previously reported for Ashe juniper (Juniperus ashei). Camphor, the predominant monoterpene in Ashe juniper, was 49.6% of the mix and was the monoterpene analyzed for this study. Blood samples were taken at 15 time points from 0 to 8 h after dosing. Concentrations of camphor were measured in plasma using solid phase extraction and gas chromatography/flame-ionization detection analysis. Maximal plasma concentration of camphor was greater for LJC than HJC (P = 0.01), and area under the curve extrapolated to infinity was greater for LJC than HJC (P < 0.01). Total systemic exposure (area under the curve) to camphor was 5 times less in HJC goats. We conclude that 1) HJC goats possess internal mechanisms to reduce the bioavailability of camphor, and 2) a blood sample taken at 45 rain or at 60 rain after intraruminal administration of camphor may be useful for identifying HJC individual animals from within large populations of goats. Key words: camphor, goat, juniper, monoterpene, pharmacokinetics doi: 10.2527/jas.2009-2585

Data from goats (n = 505), collected over a 4-yr period, were used to estimate the heritability of juniper consumption. Juniper consumption was determined by near-infrared spectroscopy on fecal samples (n = 1,080) collected from female Boer-cross goats grazing pastures with a variety of plants, including juniper. The animals with records were progeny of 72 sires. Individual goats had from 1 to 4 observations over a 4-yr period. Predicted juniper consumption for individual observations ranged from -5 to +62% of the diet. Data were analyzed with a mixed model that included management group as a fixed effect, BW as a covariate, and permanent environment, animal, and residual as random effects. Management group was a significant source of variation. Least squares means of juniper consumption, as a percentage of the total intake, for management groups varied from 19 to 47%. Heritability of juniper consumption was 13%. Repeatability of juniper consumption was 31%. These results suggest that progress to selection for goats that will consume greater amounts of juniper is obtainable, but is expected to be slow. Key words: diet selection, goat, juniper

The effects of breed, sex, and age of goats on fecal near-infrared reflectance spectroscopy-predicted percentage juniper in the diet were investigated, as were spectral differences in feces from goats differing in estimated genetic merit for juniper consumption. Eleven goats from each breed, sex, and age combination, representing 2 breeds (Angora and meattype), 3 sex classifications (female, intact male, and castrated male), and 2 age categories [adult and kid (less than 12 mo of age)] were fed complete, pelleted rations containing 0 or 14% juniper. After 7 d on the same diet, fecal samples were collected for 3 d, and the spectra from the 3 replicate samples were averaged. Fecal samples were assigned to calibration or validation data sets. In a second experiment, Angora and meat goats with high or low estimated genetic merit for juniper consumption were fed the same diet to determine the effect of consumer group on fecal spectra. Feces were scanned in the 1,100- to 2,500-nm range with a scanning reflectance monochromator. Fecal spectra were analyzed for the difference in spectral characteristics and for differences in predicted juniper in the diet using internal and independent calibration equations. Internal calibration had a high precision ([R.sup.2] = 0.94), but the precision of independent validations ([r.sup.2] = 0.56) was low. Spectral differences were affected by diet, sex, breed, and age (P [less than or equal to] 0.04). However, diet was the largest source of variation in spectral differences. Predicted percentage of juniper in the diet also showed that diet was the largest source of variation, accounting for 95% of the variation in predictions from internal calibrations and 51% of the variation in independent validations. Predictions from independent calibrations readily detected differences (P [less than or equal to] 0.001) in the percentage of juniper in the 2 diets, and the predicted differences were similar to the actual differences. Predicted juniper in the diet was also affected by sex. Feces from goats from different juniper consumer groups fed a common diet were spectrally different, and the difference may have resulted from a greater intake by high- compared with low-juniper-consuming goats. Fecal near-infrared reflectance spectroscopy predictions of botanical composition of diets should be considered an interval scale of measurement. Key words: diet composition, feces, goat, juniper, near-infrared reflectance spectroscopy

Some observers feel unless White House staff responsible for disclosing classified information to the press admit responsibility, a cover-up will probably be necessary. The most reliable process for discovering the truth will be a criminal investigation, since although the security leak may not have been criminal, a cover-up would be.

When dangers increase, liberties shrink. That has been our history, especially in wartime. And today we face dangers without precedent: a mass movement of militant Islamic terrorists who crave martyrdom, […]

Research has been conducted on the X-ray structurally characterized rhenium complexes. The preparation of these complexes from the protected amine-diamine-thiol ligands is discussed.

The legacy of former Supreme Court Justice Byron R. White is examined, focusing on his belief in judicial restraint. Topics include White's respect for the constitution, for representative democracy, and his view that the Constitution offered no support for abortion even though he favored it as a social policy.

Research is presented concerning the use of backcrossing and crossbreeding experiments involving atherosclerosis-resistant and atherosclerosis-susceptible species of pigeons to determine the inheritance of susceptibility to the disease.

Research was conducted to examine the synthesis, structure and solution forms of anti- and syn-Reo(L-cysteine-acetyl-cysteamine) and the dimethyl derivatives anti- and syn-ReO(L-penicillamine-acetyl-cysteamine). Results indicate that the introduction of an electron-withdrawing group into the ligand may lower the NH pKa of the complex below the physiologically relevant range and yield a species with a well-defined charge.

A novel method for investigating changes in fluxional Re(V)=O complexes of the analogous meso N2S2 ligands using nuclear magnetic resonance spectroscopy was developed. The new strategy used ligands with selected stereochemical features such as meso isomers of EC-type ligands. It was found that ReO has predominant from between pH 6 and 10 with the usual N2S2 basal donors. This form contains unusual determinant of chirality.