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Background Children hospitalized with severe acute malnutrition (SAM) have poor long-term outcomes following discharge, with high rates of mortality, morbidity, and impaired neurodevelopment. There is currently minimal guidance on how to support children with SAM following discharge from inpatient treatment. Objectives This systematic review and meta-analysis aimed to examine whether postdischarge interventions can improve outcomes in children recovering from complicated SAM. Methods Systematic searches of 4 databases were undertaken to identify studies of interventions delivered completely or partially after hospital discharge in children aged 6–59 mo, following inpatient treatment of SAM. The main outcome of interest was mortality. Random-effects meta-analysis was undertaken where ≥2 studies were sufficiently similar in intervention and outcome. Results Ten studies fulfilled the inclusion criteria, recruiting 39–1781 participants in 7 countries between 1975 and 2015. Studies evaluated provision of zinc (2 studies), probiotics or synbiotics (2 studies), antibiotics (1 study), pancreatic enzymes (1 study), and psychosocial stimulation (4 studies). Six studies had unclear or high risk of bias in ≥2 domains. Compared with standard care, pancreatic enzyme supplementation reduced inpatient mortality (37.8% compared with 18.6%, P

Introduction: Acetaminophen (APAP) is the most common medication taken in the United States. Using the 2003-2004 U.S. National Health and Nutrition Examination Survey (NHANES), the authors previously explored and reported the relationship of concomitant consumption of light to moderate alcohol (LMA) and therapeutic doses of APAP to early risk of renal dysfunction among adults in the United States. Statistically significant increased odds of renal dysfunction were noted among respondents who reported use of therapeutic doses of APAP and LMA by adjusting for hypertension, diabetes, and obesity. In this study the authors explored further on of potential disparities in the above relationship in the population. The relationship was verified with the 2009 Chronic Kidney Disease-Epidemiology Collaboration creatine-based estimated Glomerular Filtration Rate (GFR). Methods: Subgroup logistic regression analyses to assess disparities based on gender, race, age, education, and income were performed for renal dysfunction measured in terms of serum creatinine (SCr) directly as well as self-report using NHANES 2003-2004 data. Results: Early stage renal dysfunction, as determined by self-reports, and SCr and GFR values may occur among those who concomitantly ingested therapeutic doses of APAP and described alcohol use when compared to those who do not. Risks were more profound among females, particularly in minority racial groups, below legal drinking age of 21, and with household income below $25K. Conclusion: Potential risks for renal dysfunction are apparent in a disparate manner resulting in possible health inequity. Further research could increase the sample size of minority groups and specifically assess for effect modifiers that NHANES does not include for assessment.

Author(s): Balcomb, Christie C; Heller, Meera C; Chigerwe, Munashe; Knych, Heather K; Meyer, Allison M | Abstract: BackgroundAbomasal ulceration is recognized in neonatal and adult cattle, but research regarding treatment is limited. Histamine-2 receptor antagonists (H2 RA), such as famotidine, are used clinically with little evidence-based research about efficacy in adult cattle.Hypothesis and objectivesIntravenous famotidine administered at 0.4 mg/kg will increase the pH of abomasal outflow digesta compared to saline control in adult cattle. The objectives were to assess the effect of famotidine, administered as a single dose and as multiple doses, on abomasal outflow fluid pH in adult cattle. A third objective was to describe the pharmacokinetic parameters of IV famotidine in cattle.AnimalsFour clinically healthy adult Angus-cross steers previously fitted with duodenal cannulae placed orad to the biliary and pancreatic ducts.MethodsRandomized, 2-way cross-over clinical trial. Steers received IV famotidine (0.4 mg/kg) as a single and 3-dose regimen (every 8 hours) versus saline control. Blood for analysis of serum famotidine concentration was collected intermittently for 12 hours, and abomasal outflow fluid pH was measured at intervals for a 24-hour period. After a 34-hour washout period, the opposite treatments were administered and the sampling repeated.ResultsAbomasal outflow fluid pH was higher in steers treated with famotidine for up to 4 hours after a single dose but the effect decreased with subsequent doses. The median (range) elimination half-life was 3.33 (3.21-3.54) hours.Conclusions and clinical importanceFamotidine may be useful for treatment or prevention of abomasal ulceration in adult cattle, but the duration of effect may decrease with time.

The N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) mouse model is an attractive model system of muscle-invasive bladder cancer (MIBC) as it recapitulates the histology of human tumors in a background with intact immune system. However, it was unknown whether this carcinogen-induced model also mimicked human MIBC at the molecular and mutational level. In our study, we analyzed gene expression and mutational landscape of the BBN model by next-generation sequencing followed by a bioinformatic comparison to human MIBC using data from The Cancer Genome Atlas and other repositories. BBN tumors showed overexpression of markers of basal cancer subtype, and had a high mutation burden with frequent Trp53 (80%), Kmt2d (70%), and Kmt2c (90%) mutations by exome sequencing, similar to human MIBC. Many variants corresponded to human cancer hotspot mutations, supporting their role as driver mutations. We extracted two novel mutational signatures from the BBN mouse genomes. The integrated analysis of mutation frequencies and signatures highlighted the contribution of aberrations to chromatin regulators and genetic instability in the BBN tumors. Together, our study revealed several similarities between human MIBC and the BBN mouse model, providing a strong rationale for its use in molecular and drug discovery studies.

OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep. ANIMALS 16 healthy adult mixed-breed sheep. PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration. RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.

Aims: To survey eye care practitioners from around the world regarding their current practice for anterior eye health recording to inform guidelines on best practice. Methods: The on-line survey examined the reported use of: word descriptions, sketching, grading scales or photographs; paper or computerised record cards and whether these were guided by proforma headings; grading scale choice, signs graded, level of precision, regional grading; and how much time eye care practitioners spent on average on anterior eye health recording. Results: Eight hundred and nine eye care practitioners from across the world completed the survey. Word description (p

Mechanisms underlying motor neuron degeneration in spinal muscular atrophy (SMA), the leading inherited cause of infant mortality, remain largely unknown. Many studies have established the importance of hyperphosphorylation of the microtubule-associated protein tau in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, tau phosphorylation in SMA pathogenesis has yet to be investigated. Here we show that tau phosphorylation on serine 202 (S202) and threonine 205 (T205) is increased significantly in SMA motor neurons using two SMA mouse models and human SMA patient spinal cord samples. Interestingly, phosphorylated tau does not form aggregates in motor neurons or neuromuscular junctions (NMJs), even at late stages of SMA disease, distinguishing it from other tauopathies. Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because tau phosphorylation at these sites is significantly reduced in Cdk5 knock-out mice; genetic knock-out of Cdk5 activating subunit p35 in an SMA mouse model also leads to reduced tau phosphorylation on S202 and T205 in theSMA;p35−/−compound mutant mice. In addition, expression of the phosphorylation-deficient tauS202A,T205A mutant alleviates motor neuron defects in a zebrafish SMA modelin vivoand mouse motor neuron degeneration in culture, whereas expression of phosphorylation-mimetic tauS202E,T205E promotes motor neuron defects. More importantly, genetic knock-out oftauin SMA mice rescues synapse stripping on motor neurons, NMJ denervation, and motor neuron degenerationin vivo. Altogether, our findings suggest a novel mechanism for SMA pathogenesis in which hyperphosphorylation of non-aggregating tau by Cdk5 contributes to motor neuron degeneration.

For many decades, health specialists have successfully used their clinical ingenuity to increase the efficiency of opiate detoxification protocols. However, even if drop-out rate has decreased significantly in today's protocols, relapse after opiate detoxification remains a major problem. Therefore, naltrexone hydrochloride, an opiate antagonist, has been considered by many as a potential tool to support abstinence in what has been called “antagonist-assisted abstinence” (AAA). Nevertheless, while naltrexone implants are becoming more accessible, a large majority of centers still use oral naltrexone and adherence to treatment remains a major obstacle to AAA's efficiency. As the personality profile could give an insight into compliance, we investigated the relationship between personality profiles and naltrexone adherence in a cohort of 30 patients. The results indicate that the Axis II profile influences the likely pattern of oral naltrexone compliance. As clinicians need to identify opiate dependent patients who are most likely to benefit from oral naltrexone treatment, it therefore carries important implications and could lead to a better adjustment of therapeutic strategies for opiate dependent patients.

The phenylacetic acid (PAA) degradation pathway is a widely distributed funneling pathway for the catabolism of aromatic compounds, including the environmental pollutants styrene and ethylbenzene. However, bacterial chemotaxis to PAA has not been studied. The chemotactic strain Pseudomonas putida F1 has the ability to utilize PAA as a sole carbon and energy source. We identified a putative PAA degradation gene cluster ( paa ) in P. putida F1 and demonstrated that PAA serves as a chemoattractant. The chemotactic response was induced during growth with PAA and was dependent on PAA metabolism. A functional cheA gene was required for the response, indicating that PAA is sensed through the conserved chemotaxis signal transduction system. A P. putida F1 mutant lacking the energy taxis receptor Aer2 was deficient in PAA taxis, indicating that Aer2 is responsible for mediating the response to PAA. The requirement for metabolism and the role of Aer2 in the response indicate that P. putida F1 uses energy taxis to detect PAA. We also revealed that PAA is an attractant for Escherichia coli ; however, a mutant lacking a functional Aer energy receptor had a wild-type response to PAA in swim plate assays, suggesting that PAA is detected through a different mechanism in E. coli . The role of Aer2 as an energy taxis receptor provides the potential to sense a broad range of aromatic growth substrates as chemoattractants. Since chemotaxis has been shown to enhance the biodegradation of toxic pollutants, the ability to sense PAA gradients may have implications for the bioremediation of aromatic hydrocarbons that are degraded via the PAA pathway.

Ethnopharmacological relevance Ginkgo biloba, which is one of the most frequently used herbal medicines, is commonly used in the management of several conditions, including memory impairment. Previously, it was reported to decrease the expression of peripheral benzodiazepine receptor and the biosynthesis of glucocorticoids, thereby regulating glucocorticoid levels. However, it is not known whether Ginkgo biloba extract regulates the function of the glucocorticoid receptor. Aim of the study We determined whether Ginkgo biloba extract and several of its chemical constituents affect the activity of human glucocorticoid receptor (hGR). Materials and methods A hGR-dependent reporter gene assay was conducted in HepG2 human hepatocellular carcinoma cells and hGR target gene expression assays were performed in primary cultures of human hepatocytes. Results Multiple lots and concentrations of the extract and several of its chemical constituents (ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide) did not increase hGR activity, as assessed by a cell-based luciferase reporter gene assay. The extract did not influence the expression of hGR target genes, including tyrosine aminotransferase (hTAT), constitutive androstane receptor (hCAR), or pregnane X receptor (hPXR), in primary cultures of human hepatocytes. Moreover, hGR antagonism by mifepristone (also known as RU486) did not attenuate the extent of induction of hCAR- and hPXR-regulated target genes CYP2B6 and CYP3A4 by Ginkgo biloba extract. Conclusion Ginkgo biloba extract, ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide are not activators of hGR. Furthermore, the extract does not influence the hGR-hCAR or the hGR-hPXR signaling pathway in primary cultures of human hepatocytes.

OBJECTIVE To evaluate the use of a percutaneous transabdominal catheter (PTC) for urinary bladder drainage in goats, sheep, and potbellied pigs with obstructive urolithiasis. DESIGN Retrospective case series. ANIMALS 43 goats, 10 sheep, and 16 potbellied pigs (all males) with obstructive urolithiasis evaluated at the University of California-Davis Veterinary Medical Teaching Hospital. PROCEDURES Medical records of goats, sheep, and potbellied pigs examined because of obstructive urolithiasis from January 2000 through December 2014 were reviewed. Records of animals for which a standard PTC had been placed into the urinary bladder as part of disease management were selected. Data were collected regarding signalment, complications associated with PTC placement, and duration of PTC placement prior to removal. RESULTS 42 of 43 goats, 5 of 10 sheep, and all potbellied pigs were castrated. Median (range) duration of PTC placement was 2 (1 to 4) days for goats, 1 (1 to 4) day for sheep, and 1 (1 to 3) day for potbellied pigs. Complications associated with PTC placement included blockage of the catheter by urine sediment, perforation of the cecum, and migration of the catheter out of the urinary bladder. CONCLUSIONS AND CLINICAL RELEVANCE Placement of a PTC into the urinary bladder allowed for effective stabilization of goats, sheep, and potbellied pigs with obstructive urolithiasis while acid-base and electrolyte imbalances were corrected. Use of a PTC should be considered for urinary bladder drainage during medical management or prior to surgical management of obstructive urolithiasis for these species.

In this chapter, we describe a highly efficient genetic modification strategy for human pancreatic progenitor cells using modified mRNA-encoding GFP and Neurogenin-3. The properties of modified mRNA offer an invaluable platform to drive protein expression, which has broad applicability in pathway regulation, directed differentiation, and lineage specification. This approach can also be used to regulate expression of other pivotal transcription factors during pancreas development and might have potential therapeutic values in regenerative medicine.

Aim To assess racial/ethnic differences in diabetes self-management behaviors and quality of care in Texas. Methods This cross-sectional study assessed self-management behaviors and quality of care in 1720 adults with diabetes in the 2002–2004 Texas Behavioral Risk Factor Surveillance Survey. Multiple logistic regression models were used for assessing the independent association between race/ethnicity, self-management behaviors, and quality of care variables controlling for covariates. SAS (SAS Institute Inc, 2002-2003) was used for statistical analysis. Results Eighteen percent of Hispanics, 14% of Blacks, and 10% of Whites reported never performing home glucose testing. Seventeen percent of Hispanics, 11% of Blacks, and 10% of Whites reported never doing home foot exam. Thirty-two percent of Hispanics, 21% of Blacks, and 16% of Whites did not have an A1C test in the prior 12 months. Twelve percent of Hispanics, 10% of Blacks, and 6% of Whites did not have a dilated eye exam in the prior 12 months. Fifty-four percent of Whites, 42% of Blacks, and 40% of Hispanics received a flu shot. Forty-nine percent of Whites, 30% of Blacks, and 26% of Hispanics received a pneumonia shot. In adjusted models, Hispanics were more likely to be sedentary (OR, 1.64; 95% CI, 1.08–2.49) compared to Whites. Blacks did not differ significantly from Whites (OR, 1.46; 95% CI, 0.92–2.34). Hispanics (OR, 1.61; 95% CI, 1.01–2.57) and Blacks (OR, 1.83; 95% CI, 1.10–3.03) were more likely to get an annual foot exam by a provider compared to Whites. Hispanics (OR, 0.54; 95% CI, 0.34–0.85) and Blacks (OR, 0.58; 95% CI, 0.35–0.98) were less likely to get a pneumonia shot compared to Whites. Conclusions Hispanics have poorer access to care and poorer health status compared to Whites or Blacks. Controlling for socioeconomic and access to care variables eliminated disparities in self-management but did not eliminate disparities in quality of diabetes care.

Aims: To survey eye care practitioners from around the world regarding their current practice for anterior eye health recording to inform guidelines on best practice. Methods: The on-line survey examined the reported use of: word descriptions, sketching, grading scales or photographs; paper or computerised record cards and whether these were guided by proforma headings; grading scale choice, signs graded, level of precision, regional grading; and how much time eye care practitioners spent on average on anterior eye health recording. Results: Eight hundred and nine eye care practitioners from across the world completed the survey. Word description (p

Objective: To describe a case of tramadol withdrawal in a neonate and treatment with clonidine after exposure to long-term maternal use of high-dose tramadol. Case Summary: A 34-week gestational age neonate displayed symptoms of tramadol withdrawal within 48 hours of delivery. Due to a confusing initial clinical picture, including presumed congenital Chlamydia, questionable seizures, and an original report of maternal use of ketorolac (Toradol), diagnosis was delayed until day of life 5. Symptoms included jitteriness, myoclonic movements, and irritability. Upon further questioning of the mother, it was revealed that she was actually taking tramadol 600–800 mg daily. The infant was placed on maintenance therapy with oral clonidine (from 1 to 3 μg/kg orally every 3 hours) until discontinuation on day of life 11. After 3 days off treatment, he began to display symptoms of withdrawal again. Clonidine was restarted at 1 μg/kg orally every 8 hours and he was discharged home on maintenance clonidine therapy at 18 days postnatal age. A 7-day tapering regimen was initiated 2 weeks after discharge, and no further withdrawal symptoms occurred. Discussion: Few published articles are available to guide clinicians on the clinical course and treatment strategies for tramadol dependence and withdrawal. In neonates, the reports are particularly sparse. Traditional agents used in neonatal opioid withdrawal are narcotics (morphine, tincture of opium, methadone), benzodiazepines (diazepam, lorazepam), and phenobarbital. Clonidine use for neonatal abstinence syndrome from narcotics has been shown to be effective alone or in combination with agents such as other opiates and chloral hydrate. Potential benefits of clonidine therapy include shorter duration of therapy, reduced withdrawal symptoms, and decreased length of hospital stay. Conclusions: Withdrawal can be prolonged in infants exposed to maternal tramadol use. Clonidine may be a safe and effective option for managing symptoms of neonatal tramadol abstinence.

Mary Ann VT Dimaguila,1,2 Peter Gal,1,3,4 Tiffany Wilson,1 John E Wimmer Jr,1,2 McCrae Smith,1,2 Rita Q Carlos,1,2 Christie C Davanzo,1,2 J Laurence Ransom1,2 1Women's Hospital of Greensboro, Cone Health, Greensboro, NC, USA; 2Piedmont Neonatology, Greensboro, NC, USA; 3Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 4Greensboro Area Health Education Center, Greensboro, NC, USA Background: A recent study showed that use of Lactobacillus reuteri as probiotic prophylaxis decreased the necrotizing enterocolitis (NEC) rate from 15.1% to 2.5% in neonates with birth weight below 1000 g. Given the controversies surrounding use of probiotics in neonatal intensive care units, we address one additional aspect of routine implementation of probiotics for NEC prophylaxis – the pharmacoeconomic impact. Methods: Using data from our initial published experience, and continuing data collection after instituting a higher dose of L. reuteri, we measured the reduction in NEC in neonates with birth weight below 1000 g. Cost savings from prior studies examining the cost and outcomes of medical and surgical NEC were used to calculate the financial impact of routine L. reuteri DSM 17938 prophylaxis. Results: Medical records for 354 neonates were reviewed, 232 in the years before introduction of L. reuteri prophylaxis and 79 who received L. reuteri prophylaxis dosed at 0.1 mL daily and 43 neonates given a total daily dose of 0.2 mL as one or two doses. The incidence of NEC was significantly lower in the neonates who received L. reuteri (two of 122 neonates [1.6%] versus 35 of 232 neonates [15.1%]). The expected benefits for our neonatal intensive care unit per 100 extremely low-birth-weight neonates treated were four fewer deaths, five fewer cases of medical NEC, eight fewer cases of surgical NEC, one less patient with short-bowel syndrome, and a cost saving of approximately $2.2 million. Conclusion: Prophylactic initiation of L. reuteri as a probiotic for prevention of NEC in neonates with birth weight ≤ 1000 g is a cost-effective strategy during their stay in neonatal intensive care. Keywords: necrotizing enterocolitis, probiotic, extremely low birth weight, Lactobacillus reuteri, pharmacoeconomics

During development, precise spatiotemporal patterns of gene expression are coordinately controlled by cis-regulatory modules known as enhancers. Their crucial role in development helped spur numerous studies aiming to elucidate the functional properties of enhancers within their physiological and disease contexts. In recent years, the role of enhancer malfunction in tissue-specific tumorigenesis is increasingly investigated. Here, we direct our focus to two primary players in enhancer regulation and their role in cancer pathogenesis: MLL3 and MLL4, members of the COMPASS family of histone H3 lysine 4 (H3K4) methyltransferases, and their complex-specific subunit UTX, a histone H3 lysine 27 (H3K27) demethylase. We review the most recent evidence on the underlying roles of MLL3/MLL4 and UTX in cancer and highlight key outstanding questions to help drive future research and contribute to our fundamental understanding of cancer and facilitate identification of therapeutic opportunities.

Background Necrotizing enterocolitis (NEC) is a disease in neonates, often resulting in death or serious medical or neurodevelopmental complications. The rate of NEC is highest in the smallest babies and many efforts have been tried to reduce the rate of NEC. In neonates born below 1500 grams, the rate of NEC has been significantly reduced with the use of various probiotics. This study examines the impact of routine use of a probiotic, Lactobacillus reuteri DSM 17938 (BioGaia®), on the rate of NEC in neonates at highest risk for developing NEC, those with birth weight ≤1000 grams. Methods This is a retrospective cohort study comparing the rates of NEC in neonates with birth weight ≤ 1000 grams. The groups are separated into those neonates born from January 2004 to June 30, 2009, before introduction of L. reuteri , and neonates born July 2009 through April 2011 who received routine L. reuteri prophylaxis. The chart review study was approved by our institutional review board and exempted from informed consent. Neonates were excluded if they died or were transferred within the first week of life. The remainder were categorized as having no NEC, medical NEC, surgical NEC, or NEC associated death. Since no major changes occurred in our NICU practice in recent years, and the introduction of L. reuteri as routine prophylaxis was abrupt, we attributed the post-probiotic changes to the introduction of this new therapy. Rates of NEC were compared using Chi square analysis with Fisher exact t-test. Results Medical records for 311 neonates were reviewed, 232 before- and 79 after-introduction of L. reuteri prophylaxis. The incidence of NEC was significantly lower in the neonates who received L. reuteri (2 of 79 neonates [2.5%] versus 35 of 232 untreated neonates [15.1%]). Rates of late-onset gram-negative or fungal infections (22.8 versus 31%) were not statistically different between treated and untreated groups. No adverse events related to use of L reuteri were noted. Conclusions Prophylactic initiation of L. reuteri as a probiotic for prevention of necrotizing enterocolitis resulted in a statistically significant benefit, with avoidance of 1 NEC case for every 8 patients given prophylaxis.

OBJECTIVE To compare the efficacy and safety of dexmedetomidine and fentanyl for sedation in mechanically ventilated premature neonates. METHODS This was a retrospective, observational case-control study in a level III neonatal intensive care unit. Forty-eight premature neonates requiring mechanical ventilation were included. Patients received fentanyl (n=24) or dexmedetomidine (n=24) for pain or sedation. Each group also received fentanyl and lorazepam boluses as needed for agitation. The primary outcomes were efficacy and frequency of acute adverse events associated with each drug. Days on mechanical ventilation, stooling patterns, feeding tolerance, and neurologic outcomes were also evaluated. RESULTS There were no significant differences in baseline demographics between the dexmedetomidine and fentanyl patients. Patients in the dexmedetomidine group required less adjunctive sedation and had more days free of additional sedation in comparison to fentanyl (54.1% vs. 16.5%, p CONCLUSIONS Dexmedetomidine was safe and effective for sedation in the premature neonates included in this study. Prospective randomized-controlled trials are needed before routine use of dexmedetomidine can be recommended.

Bilobalide is a naturally-occurring sesquiterpene trilactone with therapeutic potential in the management of ischemia and neurodegenerative diseases such as Alzheimer's disease. In the present study, we investigated the effect of bilobalide on the activity of rat constitutive androstane receptor (rCAR) and rat pregnane X receptor (rPXR) and compared that with human CAR (hCAR) and human PXR (hPXR). Bilobalide activated rCAR in a luciferase reporter gene assay and increased rCAR target gene expression in cultured rat hepatocytes, as determined by the CYP2B1 mRNA and CYP2B enzyme activity (benzyloxyresorufin O -dealkylation) assays. This increase in hepatocyte CYP2B1 expression by bilobalide was not accompanied by a corresponding increase in rCAR mRNA level. In contrast to the activation of rCAR, the activity of rPXR, hCAR, and hPXR was not influenced by this chemical in cell-based reporter gene assays. Consistent with these results, bilobalide did not alter rPXR, hCAR, or hPXR target gene expression in rat or human hepatocytes, as evaluated by the CYP3A23, CYP2B6, CYP3A4 mRNA assays and the CYP3A (testosterone 6β-hydroxylation) and CYP2B6 (bupropion hydroxylation) enzyme activity assays. Bilobalide was not an antagonist of rPXR, hCAR, or hPXR, as suggested by the finding that it did not attenuate rPXR activation by pregnenolone 16α-carbonitrile, hCAR activation by 6-(4-chlorophenyl)imidazo\[2,1- b \]\[1,3\]thiazole-5-carbaldehyde O -(3,4-dichlorobenzyl)oxime, or hPXR activation by rifampicin in reporter gene assays. In conclusion, bilobalide is an activator of rCAR, whereas it is not a ligand of rPXR, hCAR, or hPXR. Similarly, it is an inducer of rat CYP2B1, but not of rat CYP3A23, human CYP2B6, or human CYP3A4.

Conflicting data exist as to whether meclizine is an activator of human pregnane X receptor (hPXR). Therefore, we conducted a detailed, systematic investigation to determine whether meclizine affects hPXR activity by performing a cell-based reporter gene assay, a time-resolved fluorescence resonance energy transfer competitive ligand-binding assay, a mammalian two-hybrid assay to assess coactivator recruitment, and a hPXR target gene expression assay. In pregnane X receptor (PXR)-transfected HepG2 cells, meclizine activated hPXR to a greater extent than rat PXR. It bound to hPXR ligand-binding domain and recruited steroid receptor coactivator-1 to the receptor. Consistent with its hPXR agonism, meclizine increased hPXR target gene expression (CYP3A4) in human hepatocytes. However, it did not increase but decreased testosterone 6β-hydroxylation, suggesting inhibition of CYP3A catalytic activity. Meclizine has also been reported to be an inverse agonist and antagonist of human constitutive androstane receptor (hCAR). Therefore, given that certain tissues (e.g., liver) express both hPXR and hCAR and that various genes are cross-regulated by them, we quantified the expression of a hCAR- and hPXR-regulated gene (CYP2B6) in cultured human hepatocytes treated with meclizine. This drug did not decrease constitutive CYP2B6 mRNA expression or attenuate hCAR agonist-mediated increase in CYP2B6 mRNA and CYP2B6-catalyzed bupropion hydroxylation levels. These observations reflect hPXR agonism and the lack of hCAR inverse agonism and antagonism by meclizine, which were assessed by a hCAR reporter gene assay and mammalian two-hybrid assay. In conclusion, meclizine is a hPXR agonist, and it does not act as a hCAR inverse agonist or antagonist in cultured human hepatocytes.

Background: This survey was conducted to assess the status of translating research findings into practice at a major academic healthcare system in Central Texas. Methods: We conducted a cross-sectional survey addressing knowledge of and participation in translational research of physicians, residents, nurses, and third and fourth year medical students in a major academic healthcare system in Central Texas. Some of the research questions were adapted from an in-house HMORN survey (personal communication). Results: Out of 508 respondents, 428 (84.3%) completed all questions. A total of 68.9% of faculty reported having sufficient education and training to conduct research vs. 44.4% of residents and 35.6% of nurses. Fifty-eight percent of faculty, 53% of residents and 9% of nurses reported current involvement in research activity. A total of 55.6% of residents reported that their departments provide them with protected time for research vs. 18.4% of faculty and 10.3% of nurses. In addition, 33.9% of nurses reported interest in participating in research but do not know how to start. A majority of faculty and residents and 58% of nurses indicated they were familiar with translational research. Yet only 42.7% of residents and 35% of faculty, 46.7% of residents and 35.6% of nurses indicated they were aware of any changes in delivery of care that resulted from research projects. Conclusions: The study results suggested failure to leverage members of the healthcare team in a systematic process to ensure translation of research findings into practice. Results highlighted the need to merge the culture of safety and quality improvement with research while dealing with the daily pressures of patient care.

While the concept of hospice care for humans has existed for decades and is an integral part of the dying process, providing hospice care for companion animals is a new and growing service. Veterinarians and pet-owners have recently recognized that there is a need and a demand to care for pets with terminal illnesses. The Colorado State University Pet Hospice program meets those needs through supporting pets, their owners, and veterinarians, and educating professional veterinary students in end-of-life care. Developed in 2003, Pet Hospice is a student-run program that trains veterinary students in animal hospice care, and matches them with the family and veterinarian of a terminally ill pet in the community. Since its inception, 101 veterinary student volunteers have been trained and provided support to 68 families. Continued expansion of the client base, enlargement of the network of veterinarians and volunteers, and positive program evaluations reflect the strong impact of Pet Hospice and its support from veterinary students, veterinarians, and the community.

Previous reports have shown that peripheral leukocytes may be established in continuous culture from patients with a variety of diseases and also from "normal" persons [1-5]. The production of interferon has already been reported from long-term cultures of white cells derived from patients with leukemia, lymphoma [6], infectious mononucleosis [7], and viral hepatitis [8]. This paper reports the production of interferon by long-term cultures of white cells derived from patients with viral diseases (herpes simplex, mumps, herpes zoster, rubeola) and also from patients with nonviral diseases (sarcoid, rheumatic fever, multiple myeloma) and Burkitt's lymphoma. An investigation was also made to determine whether long-term cultures of white cells derived from patients with infections with herpes simplex and mumps produced interferon in association with