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Diutina catenulata (Candida catenulata) is an ascomycetous yeast that has been isolated from humans, animals and environmental sources. The species is a contaminant of dairy products, and has been linked to superficial and invasive infections in both humans and animals. Previous phylogenetic analyses have assigned the species to the Saccharomycetales, but failed to identify its specific clade. Here, we report the genome sequence of an environmental isolate of D. catenulata. Examination of the tRNA repertoire and coding potential of this species shows that it translates the CUG codon as serine and not leucine. In addition, two phylogenetic analyses using 204 ubiquitous gene family alignments and 3,826 single-copy genes both confirm the placement of the species in the Debaryomycetaceae/Metschnikowiaceae, or CTG-Ser clade. The sequenced isolate contains an MTLα idiomorph. However, unlike most MTL loci in related species, poly (A) polymerase (PAP) is not adjacent to MTLα1., Competing Interests: The authors have declared that no competing interests exist.

We report a draft genome sequence of a strain of the nonfermentative yeast Nadsonia starkeyi-henricii , isolated from soil in a forest in Ireland. Comparison to Nadsonia fulvescens shows few rearrangements and a level of divergence similar to that of Saccharomyces cerevisiae versus Saccharomyces paradoxus Its mitochondrial genome lacks NAD genes., (Copyright © 2018 O’Boyle et al.)

No genome sequence of a species from Barnettozyma , a yeast genus in the family Phaffomycetaceae, is currently available. We isolated two B. californica strains from soils in Ireland and generated draft sequences of their 11.7-Mb genomes. Single nucleotide polymorphism (SNP) analysis showed 20,490 differences between the strains and suggests that B. californica is haploid., (Copyright © 2018 Mullen et al.)

Metschnikowia strain UCD127 was isolated from soil in Ireland and sequenced. It is a highly heterozygous diploid strain with 385,000 single nucleotide polymorphisms (SNPs). Its ribosomal DNA has the highest similarity to that of M. chrysoperlae , but its ACT1 and TEF1 loci and mitochondrial genome show affinity to those of M. fructicola , whose genome is significantly larger., (Copyright © 2018 Venkatesh et al.)

Here, three researchers who have recently embarked on careers in cephalopod biology discuss the current state of the field and offer their hopes for the future. Seven major topics are explored: genetics, aquaculture, climate change, welfare, behavior, cognition, and neurobiology. Recent developments in each of these fields are reviewed and the potential of emerging technologies to address specific gaps in knowledge about cephalopods are discussed. Throughout, the authors highlight specific challenges that merit particular focus in the near-term. This review and prospectus is also intended to suggest some concrete near-term goals to cephalopod researchers and inspire those working outside the field to consider the revelatory potential of these remarkable creatures.

An adolescent male with a recent history of streptococcal pharyngitis presented with severe substernal chest pain, troponin leak, and ST-segment elevation, which are suggestive of acute inferolateral myocardial infarction. The coronary angiogram was normal. The patient was subsequently diagnosed with non-rheumatic streptococcal myocarditis. He was treated with amoxicillin and had excellent recovery. Non-rheumatic streptococcal myocarditis is an important mimic of acute myocardial infarction in young adults.

Introduction: In 2015, 11.9% of people with cystic fibrosis (CF) in the United States had osteopenia, 5.1% osteoporosis, and 0.3% experienced a fracture. Screening for CF-related bone disease starts in childhood, and dual energy x-ray absorptiometry (DXA) is the recommended method. It is unknown whether peripheral quantitative computed tomography (pQCT) can detect deficits earlier than DXA. This study compared pQCT and DXA scans in a group of pre-pubertal children with CF and healthy controls., Methods: This was a cross-sectional study of children at Tanner stage 1. A pQCT scan of the radius at proximal and distal sites was performed plus a total body DXA scan. Serum C-reactive protein, interleukin-6 and tumor necrosis factor-alpha were also measured., Results: A total of 34 subjects completed the study; 14 with CF and 20 controls. At the distal radius, pQCT showed a lower total bone mineral density (BMD) Z-score for the CF group (P = 0.01 and P = 0.03 for 2 different reference databases) compared to controls. At the proximal site, the polar strength-strain index was lower in the CF group (P = 0.017). Finally, the total body BMD Z-score by DXA was lower in the CF group, although it did not meet the definition of reduced bone density (P = 0.004). Biomarkers of inflammation were not different., Conclusions: In this group of pre-pubertal children with CF, measures of bone strength and density by both pQCT and DXA were reduced compared to healthy controls.

Aquatic invasive species (AIS) are biological pollutants that cause detrimental ecological, economic, and human-health effects in their introduced communities. With increasing globalization through maritime trade, ports are vulnerable to AIS exposure via commercial vessels. The Cuban Port of Mariel is poised to become a competitive transshipment hub in the Caribbean and the intent of this study was to evaluate present and potential impacts AIS pose with the likely future increase in shipping activity. We utilized previous assessment frameworks and publicly accessible information to rank AIS by level of threat. Fifteen AIS were identified in Cuba and one, the Asian green mussel Perna viridis (Linnaeus, 1758), had repeated harmful economic impacts. Five species associated with trade partners of Port Mariel were considered potentially detrimental to Cuba if introduced through shipping routes. The results presented herein identify species of concern and emphasize the importance of prioritizing AIS prevention and management within Cuba., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Stress experienced during prenatal development-either applied to reproducing females (maternal stress), directly to developing offspring (embryonic stress) or in combination-is associated with a range of post-natal behavioral effects in numerous organisms. We conducted an experiment to discern if maternal and embryonic stressors affect the behavior of hatchlings of the cuttlefish Sepia officinalis , a species with features that allow for the examination of these stress types in isolation. Separating the impact of stress transmitted through the mother vs. stress experienced by the embryo itself will help clarify the behavioral findings in viviparous species for which it is impossible to disentangle these effects. We also compared the effect of a naturally-occurring (predator cue) and an "artificial" (bright, randomly-occurring LED light) embryonic stressor. This allowed us to test the hypothesis that a threat commonly faced by a species (natural threat) would be met with a genetically-programmed and adaptive response while a novel one would confound innate defense mechanisms and lead to maladaptive effects. We found that the maternal stressor was associated with significant differences in body patterning and activity patterns. By contrast, embryonic exposure to stressors increased the proportion of individuals that pursued prey. From these results, it appears that in cuttlefish, maternal and embryonic stressors affect different post-natal behavior in offspring. In addition, the effect of the artificial stressor suggests that organisms can sometimes react adaptively to a stressor even if it is not one that has been encountered during the evolutionary history of the species.

Disruptions in lipid homeostasis have been observed in many neurodevelopmental disorders that are associated with dendrite morphogenesis defects. However, the molecular mechanisms of how lipid homeostasis affects dendrite morphogenesis are unclear. We find that easily shocked (eas), which encodes a kinase with a critical role in phospholipid phosphatidylethanolamine (PE) synthesis, and two other enzymes in this synthesis pathway are required cell autonomously in sensory neurons for dendrite growth and stability. Furthermore, we show that the level of Sterol Regulatory Element-Binding Protein (SREBP) activity is important for dendrite development. SREBP activity increases in eas mutants, and decreasing the level of SREBP and its transcriptional targets in eas mutants largely suppresses the dendrite growth defects. Furthermore, reducing Ca 2+ influx in neurons of eas mutants ameliorates the dendrite morphogenesis defects. Our study uncovers a role for EAS kinase and reveals the in vivo function of phospholipid homeostasis in dendrite morphogenesis., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cuttlefish are highly visual animals, a fact reflected in the large size of their eyes and visual-processing centers of their brain. Adults detect their prey visually, navigate using visual cues such as landmarks or the e -vector of polarized light and display intense visual patterns during mating and agonistic encounters. Although much is known about the visual system in adult cuttlefish, few studies have investigated its development and that of visually-guided behavior in juveniles. This review summarizes the results of studies of visual development in embryos and young juveniles. The visual system is the last to develop, as in vertebrates, and is functional before hatching. Indeed, embryonic exposure to prey, shelters or complex background alters postembryonic behavior. Visual acuity and lateralization, and polarization sensitivity improve throughout the first months after hatching. The production of body patterning in juveniles is not the simple stimulus-response process commonly presented in the literature. Rather, it likely requires the complex integration of visual information, and is subject to inter-individual differences. Though the focus of this review is vision in cuttlefish, it is important to note that other senses, particularly sensitivity to vibration and to waterborne chemical signals, also play a role in behavior. Considering the multimodal sensory dimensions of natural stimuli and their integration and processing by individuals offer new exciting avenues of future inquiry.

Though a mollusc, the cuttlefish Sepia officinalis possesses a sophisticated brain, advanced sensory systems, and a large behavioral repertoire. Cuttlefish provide a unique perspective on animal behavior due to their phylogenic distance from more traditional (vertebrate) models. S. officinalis is well-suited to addressing questions of behavioral ontogeny. As embryos, they can perceive and learn from their environment and experience no direct parental care. A marked progression in learning and behavior is observed during late embryonic and early juvenile development. This improvement is concomitant with expansion and maturation of the vertical lobe, the cephalopod analog of the mammalian hippocampus. This review synthesizes existing knowledge regarding embryonic and juvenile development in this species in an effort to better understand cuttlefish behavior and animal behavior in general. It will serve as a guide to future researchers and encourage greater awareness of the utility of this species to behavioral science., (© 2016 Wiley Periodicals, Inc.)

Objective: To compare survey responses between licensed pharmacists who work with or employ new graduates and graduating senior pharmacy students at a college of pharmacy., Design: This was a retrospective analysis of surveys given to 2 groups of pharmacists and students. Responses to items regarding importance of desirable qualities in new pharmacists and level of preparation of new graduates were analyzed. Qualities included drug information, pharmacology, therapeutics, communication with patients/customers or health care professionals, professionalism, ethics, management, and conflict resolution., Results: There was consensus between pharmacists and students regarding the importance of all items ( P > .05 for all comparisons). However, the percentage of pharmacists versus students who agreed that new graduates communicate effectively differed (86.7% vs 100%, respectively, P < .05). Of pharmacists surveyed at a career fair, 64.1% chose communication as the 1 skill that would distinguish an applicant, and retail and hospital pharmacists displayed a statistically significant ( P < .05) difference in the audience (patients/customers vs other health care professionals)., Conclusion: Pharmacists and students agree on the knowledge and skills essential for pharmacy practice but disagree on the level of preparation for effective communication. These results support ongoing efforts to improve the development of communication skills in the professional pharmacy curriculum.

Background: There is little evidence in the medical literature to guide empiric treatment of pediatric patients with long-term tracheostomies who present with signs and symptoms of a bacterial respiratory infection. The overall goal of this study was to describe the respiratory microbiology in this study population at our institution., Methods: This study was a retrospective chart review of all subjects with tracheostomies currently receiving care at the Arkansas Center for Respiratory Technology Dependent Children. Descriptive statistics were used to describe the respiratory microbiology of the full study group. Several subgroup analyses were conducted, including description of microbiology according to time with tracheostomy, mean time to isolation of specific organisms after the tracheostomy tube was placed, association between Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus isolation and prescribed antibiotic courses, and description of microbiology according to level of chronic respiratory support. Available respiratory culture results up to July 2011 were collected for all eligible subjects. Descriptive statistics were used to describe subject characteristics, and chi-square analysis was used to analyze associations between categorical data. P < .05 was considered statistically significant., Results: A total of 93 subjects met inclusion criteria for the study. The median (interquartile range) age at time of tracheotomy was 0.84 (0.36-3.25) y, and the median (interquartile range) time with tracheostomy was 4.29 (2.77-9.49) y. The most common organism isolated was P. aeruginosa (90.3%), with Gram-negative organisms predominating. However, 55.9% of the study population had a respiratory culture positive for methicillin-resistant S. aureus. The first organism isolated after tracheostomy placement was Methiciliin-sensitive S. aureus was isolated the soonest after tracheostomy placement. Specific organisms were not related to level of chronic respiratory support or likelihood of receiving antibiotics., Conclusions: This study provides an updated overview of the variety of potential pathogens isolated from respiratory cultures of pediatric subjects with long-term tracheostomies., (Copyright © 2016 by Daedalus Enterprises.)

Background: Beclin 1 is a key regulator of multiple trafficking pathways, including autophagy and receptor recycling in yeast and microglia. Decreased beclin 1 levels in the CNS result in neurodegeneration, an effect attributed to impaired autophagy. However, neurons also rely heavily on trophic factors, and signaling through these pathways requires the proper trafficking of trophic factor receptors., Results: We discovered that beclin 1 regulates signaling through the neuroprotective TGF-β pathway. Beclin 1 is required for recycling of the type I TGF-β receptor ALK5. We show that beclin 1 recruits the retromer to ALK5 and facilitates its localization to Rab11(+) endosomes. Decreased levels of beclin 1, or its binding partners VPS34 and UVRAG, impair TGF-β signaling., Conclusions: These findings identify beclin 1 as a positive regulator of a trophic signaling pathway via receptor recycling, and suggest that neuronal death induced by decreased beclin 1 levels may also be due to impaired trophic factor signaling.

Rationale: The treatment of children with severe-persistent asthma remains problematic. Recent studies suggest that stratification of this cohort by inflammatory type may be useful in designing effective treatment strategies. In this study, we examined the inflammatory profile in bronchoalveolar lavage fluid from children with severe-persistent asthma and compared this profile with serum IgE levels., Methods: The inflammatory profile in the bronchoalveolar fluid from 32 children who met criteria for severe-persistent asthma as defined by the Severe Asthma Research Program (SARP) were analyzed retrospectively. Inflammatory patterns were classified as neutrophilic, eosinophilic, mixed, or pauci-granulocytic. Serum total IgE was measured prior to bronchoscopy and determined by ELISA at each hospital's lab by standard procedures., Results: The most common pattern of inflammation in this cohort was neutrophilic (37.5%) followed by eosinophilic (28.1%), mixed (21.9%), and pauci-granulocytic (11.1%). The odds ratio of an eosinophilic BAL pattern for patients with an elevated serum IgE was 4.67 (CI 0.78-28, P = 0.12). A correlation between serum IgE levels and BAL eosinophil percentages was present (P = 0.04)., Conclusions: To our knowledge, ours is one of few studies to systematically investigate the pattern of lower airway inflammation in children with severe-persistent asthma. Our results differ from a recent investigation in children, showing more heterogeneity and a greater proportion of neutrophilic inflammation. Further investigation is required to determine whether specific inflammatory patterns are associated with specific etiologies, and whether individualized therapy is warranted., (© 2015 Wiley Periodicals, Inc.)

A hallmark of cystic fibrosis (CF) lung disease is neutrophilic airway inflammation. Elevated neutrophil counts have been associated with decreased forced expiratory volume in 1 second and poor clinical measures in patients with CF. Interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78), tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) contribute to neutrophil activation and disease pathogenesis in the airways of patients with CF. Drugs that modify the production of these chemokines in the airways could potentially benefit CF patients. Thus, we determined the effects of fenofibrate on their production in cell populations obtained from the airways. Human small airway epithelial cells and CF bronchial epithelial cells were treated with IL-1β to induce inflammation. We cotreated the cells with fenofibrate at concentrations ranging from 10 to 50 μM to determine if this drug could attenuate the inflammation. IL-8, ENA-78, TNF-α, GM-CSF, and G-CSF production were measured from the cell culture supernates by ELISA. ANOVA statistical testing was conducted using SPSS 17.0. IL-1β increased the production of each of the chemokines by several fold. Fenofibrate reduced IL-1β induced production of each of these neutrophilic chemokines at the concentrations used. IL-1β increases the production of neutrophilic chemokines in airway epithelial cells. Cotreatment with fenofibrate blunts these processes. Fenofibrate should be explored as a therapeutic option to modulate the abundant neutrophilic inflammation observed in CF., (© 2015 Wiley Periodicals, Inc.)

Purpose: There is conflicting evidence regarding the association between montelukast and neuropsychiatric events (NE). We sought to examine this association among children with asthma., Methods: Using a 10% sample of the LifeLink Health Plan Claims data, subjects less than 18 years of age with a primary diagnosis of asthma between 1 January 1998 and 31 December 2009 were identified. A range of case definitions for NE was formulated based on diagnoses of psychiatric disorders and use of psychotropic medications. Using a matched nested case-control design, three controls were matched to each case on age, gender and geographic region, and assigned a matching index date. Exposure to montelukast was measured as any exposure during the year, recency of exposure, cumulative duration of exposure, and cumulative dose. Conditional logistic regression was used to estimate unadjusted and adjusted odds ratio (OR) controlling for potential confounders., Results: Using the broadest case definition, 1920 cases were identified. Subjects exposed to montelukast during the prior year had an unadjusted OR of 1.09 (95%CI [0.96, 1.22]) and adjusted OR of 1.01 (95%CI [0.88, 1.14]) for experiencing NE measured using the broadest definition. A clear dose-response relationship was not observed. Exposure to a moderate chronic cumulative dose of montelukast (481 mg-1050 mg) had a higher odds of being diagnosed with neuropsychiatric disturbances (OR = 1.27; 95%CI [1.03, 1.57]) while exposure to high cumulative doses (>1050 mg) had a lower odds (OR = 0.64; 95%CI [0.50, 0.82])., Conclusions: These data did not detect a consistent significant positive association between montelukast and NE in children with asthma., (Copyright © 2015 John Wiley & Sons, Ltd.)

Despite the frequent isolation of nitrate-respiring Epsilonproteobacteria from deep-sea hydrothermal vents, the genes coding for the nitrate reduction pathway in these organisms have not been investigated in depth. In this study we have shown that the gene cluster coding for the periplasmic nitrate reductase complex (nap) is highly conserved in chemolithoautotrophic, nitrate-reducing Epsilonproteobacteria from deep-sea hydrothermal vents. Furthermore, we have shown that the napA gene is expressed in pure cultures of vent Epsilonproteobacteria and it is highly conserved in microbial communities collected from deep-sea vents characterized by different temperature and redox regimes. The diversity of nitrate-reducing Epsilonproteobacteria was found to be higher in moderate temperature, diffuse flow vents than in high temperature black smokers or in low temperatures, substrate-associated communities. As NapA has a high affinity for nitrate compared with the membrane-bound enzyme, its occurrence in vent Epsilonproteobacteria may represent an adaptation of these organisms to the low nitrate concentrations typically found in vent fluids. Taken together, our findings indicate that nitrate reduction is widespread in vent Epsilonproteobacteria and provide insight on alternative energy metabolism in vent microorganisms. The occurrence of the nap cluster in vent, commensal and pathogenic Epsilonproteobacteria suggests that the ability of these bacteria to respire nitrate is important in habitats as different as the deep-sea vents and the human body.

Beclin 1 has a well-established role in regulating autophagy, a cellular degradation pathway. Although the yeast ortholog of beclin 1 (Atg6/Vps30) was discovered to also regulate vacuolar protein sorting nearly 30 years ago, the varied functions of beclin 1 in mammalian cells are only beginning to be sorted out. We recently described a role for beclin 1 in regulating recycling of phagocytic receptors in microglia, a function analogous to that of its yeast ortholog. Microglia lacking beclin 1 have a reduced phagocytic capacity, which impairs clearance of amyloid β (Aβ) in a mouse model of Alzheimer's Disease (AD). Here we summarize these findings and discuss the implications for beclin 1-regulated receptor recycling in neurodegenerative disease.

Patients with cystic fibrosis (CF) have several risk factors for Clostridium difficile colonization such as frequent hospitalization and exposure to a broad array of antibiotics utilized for the control, eradication, and prophylaxis of respiratory pathogens. However, despite this high rate of colonization, the occurrence of C. difficile infection (CDI) in CF is rare. We report three children with CF who presented with severe community-associated CDI. All three children had complicated courses and one died. These children were in good health without significant morbidities, and were not frequently hospitalized nor did they receive frequent antibiotic courses. The occurrence of 3 severe cases within a 15-month period prompted us to report these cases and review the literature in regard to CDI. We reviewed the CF GI tract as possible risk factors for a high rate of C. difficile colonization in individuals with CF. Since a high percentage of individuals with CF are on gastric acid blocking agents, we also focused on gastric acid suppression as a potential risk factor for CDI., (© 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.)

Purpose: The blood neutrophil to lymphocyte ratio (NLR) has been identified as a potentially useful marker of clinical outcome in disease states with an inflammatory component. The objective of this study was to evaluate the relationship between NLR and clinical status in children with cystic fibrosis., Methods: This was a retrospective chart review. Data collected included NLR, body mass index, and forced expiratory volume in 1 second (FEV1) while asymptomatic, and during hospitalizations for pulmonary exacerbation. An NLR breakpoint of 3 was used for comparisons of body mass index and FEV1., Results: A total of 159 charts were reviewed. An NLR ≥ 3 was significantly associated with lower body mass index and lower FEV1. NLR during hospitalization was significantly higher than NLR while asymptomatic. NLR measured during the first 3 months of life was negatively correlated with FEV1 at age 12., Conclusion: NLR correlates with clinical status in children with cystic fibrosis and may be a useful biomarker in this population.

Phagocytosis controls CNS homeostasis by facilitating the removal of unwanted cellular debris. Accordingly, impairments in different receptors or proteins involved in phagocytosis result in enhanced inflammation and neurodegeneration. While various studies have identified extrinsic factors that modulate phagocytosis in health and disease, key intracellular regulators are less understood. Here we show that the autophagy protein beclin 1 is required for efficient phagocytosis in vitro and in mouse brains. Furthermore, we show that beclin 1-mediated impairments in phagocytosis are associated with dysfunctional recruitment of retromer to phagosomal membranes, reduced retromer levels, and impaired recycling of phagocytic receptors CD36 and Trem2. Interestingly, microglia isolated from human Alzheimer's disease (AD) brains show significantly reduced beclin 1 and retromer protein levels. These findings position beclin 1 as a link between autophagy, retromer trafficking, and receptor-mediated phagocytosis and provide insight into mechanisms by which phagocytosis is regulated and how it may become impaired in AD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Cystic fibrosis (CF) affects approximately 30,000 people in the United States and is characterized by pulmonary disease and poor nutrition. Optimal nutrition is associated with better pulmonary function, and aggressive nutrition interventions have played a major role in increased survival. Even though the CF Foundation (CFF) has published treatment guidelines for certain areas of nutrition care, there may still be variability in other areas. Thus, the purpose of this study was to survey current practices among CF dietitians., Materials and Methods: A 25-item web-based survey was developed and sent to nutrition professionals via the CFF nutrition listserv. Responses were anonymous. Areas of practice surveyed included nutrition care for infants, pancreatic enzyme replacement, vitamins and bone health, and miscellaneous practices. Descriptive statistics were used to report the results., Results: Among the 76 respondents (21% response rate), there was general agreement regarding nutrition practices for infants and pancreatic enzyme replacement. Responses varied regarding enzyme administration with gastrostomy tube feeds and in practices related to bone health. Of miscellaneous practices, there was agreement regarding zinc supplementation and appetite stimulants. However, opinions varied regarding concern for coronary artery disease with the CF high-fat diet. Practices related to use of acid blockers also varied., Conclusion: The results of this survey demonstrate good agreement among nutrition professionals in some areas and variability in others for the nutrition management of patients with CF. Areas of variability point to the need for further research and continued additions to the guidelines and consensus statements.

Objective: To describe the use of lubiprostone for constipation in 3 adults with cystic fibrosis (CF)., Case Summary: This case series describes the use of lubiprostone for the treatment of constipation in 3 adults with CF (mean +/- SD length of therapy 17.3 +/- 1.5 mo). All 3 patients were prescribed lubiprostone 24 microg twice daily after hospitalization for treatment of intestinal obstruction. Patient 1 continues on chronic polyethylene glycol (PEG) 3350 and lubiprostone and has not had a recurrence of obstruction. Patient 2 requires aggressive chronic therapy with PEG 3350, lubiprostone, and methylnaltrexone. She has had 1 recurrence of obstruction. Patient 3 continues with lubiprostone taken several times per week with good control of constipation and no recurrence of obstruction to date. The adverse effect profile has been tolerable in all 3 patients., Discussion: CF is caused by a genetic mutation resulting in a dysfunctional or absent CF transmembrane conductance regulator that normally functions as a chloride channel. This results in viscous secretions in multiple organ systems including the lungs and intestinal tract. Accumulation of viscous intestinal contents contributes to constipation, which is common among adults with CF and can sometimes lead to intestinal obstruction. Lubiprostone is indicated for chronic constipation and works by activating type 2 chloride channels (ClC-2) in the intestinal tract. Because it utilizes an alternate chloride channel, lubiprostone may be especially effective for constipation in patients with CF., Conclusions: Lubiprostone provides an additional option for the treatment of constipation in adults with CF. Its use in the CF population deserves further study.

Alternative medicine is becoming increasingly popular, especially with terminally ill patients. Most alternative remedies have not been adequately studied or proven effective for the diseases for which they are promoted. In the worst cases, these therapies are harmful. We describe a 16-year-old girl with metastatic hepatocellular carcinoma who experienced cesium-induced QT-interval prolongation after the start of a cesium chloride-based alternative treatment regimen. She had received seven courses of chemotherapy, with a cumulative doxorubicin dose of 500 mg/m(2) over 5 months, resulting in minimal tumor regression. Against the advice of her oncologist, she abandoned traditional therapy and started an alternative regimen that included cesium chloride supplements. Two weeks later, the patient went to a local emergency department after experiencing two brief syncopal episodes. An electrocardiogram revealed occasional premature ventricular contractions, a QTc interval of 683 msec (normal range for females 450-460 msec), and R on T phenomenon. She was admitted to the hospital and later experienced monomorphic ventricular tachycardia, which resolved spontaneously. Lidocaine therapy was started, and the patient was transferred to a cardiac intensive care unit at our hospital. Her plasma cesium level was 2400 microg/dl (normal < 1 microg/dl), and her family was told to stop her alternative treatment regimen. On hospital day 5, as no additional arrhythmias had occurred, lidocaine was discontinued. Two days later, the patient's QTc interval had decreased to 546 msec, and she was discharged home. Two months later, at a follow-up visit, her serum cesium level was 1800 microg/dl, and her QTc interval was 494 msec. According to the Naranjo adverse drug reaction probability scale, cesium was the probable cause of the patient's arrhythmia. In animal models, cesium chloride has induced cardiac arrhythmias, including torsade de pointes. It inhibits delayed rectifier potassium channels in the myocardium, causing delayed repolarization and QT-interval prolongation. Patients with cancer should be aware that alternative remedies may be harmful and ineffective. Because patients may be unlikely to self-report alternative remedies, health care providers should specifically ask their patients about any alternative treatments they may be taking and should be knowledgeable about their toxicities.

Objectives: To evaluate a rubric-based method of assessing pharmacy students' case presentations in the recitation component of a therapeutics course., Methods: A rubric was developed to assess knowledge, skills, and professional behavior. The rubric was used for instructor, student peer, and student self-assessment of case presentations. Rubric-based composite scores were compared to the previous dichotomous checklist-based scores., Results: Rubric-based instructor scores were significantly lower and had a broader score distribution than those resulting from the checklist method. Spring 2007 rubric-based composite scores from instructors and peers were significantly lower than those from the pilot study results, but self-assessment composite scores were not significantly different., Conclusions: Successful development and implementation of a grading rubric facilitated evaluation of knowledge, skills, and professional behavior from the viewpoints of instructor, peer, and self in a didactic course.

The objective was to analyze interrelationships among plasma zinc (PZ), plasma prolactin (PRL), milk transfer, and milk zinc from a longitudinal study of lactating women with a range of zinc intakes. Sixteen of 26 women received a 15 mg/d zinc supplement, resulting in a significant increase in total zinc intake compared with nonsupplemented participants (P<.001). No significant differences in key variables were observed between the zinc-supplemented and non-zinc-supplemented women; data were thus combined. An inverse trend between PRL and PZ was observed at 0.5 (r=-.36, P=.08) and 7 months (r=-.38, P=.06). Correlations between PRL at 0.5 months and at 3, 5, and 7 months were significant (r>.50, P<.01). PRL concentrations and milk transfer were positively correlated at 5 (r=.67, P<.001) and 7 months (r=.53, P<.01), consistent with PRL role in lactation maintenance. Studies including zinc-deficient lactating women are required to clarify the interrelationships between zinc status and PRL secretion.

The effect of housing conditions on sulpiride-induced increases in extracellular dopamine (DA) levels was investigated in the nucleus accumbens (NAC) of P rats. Rats were double-housed (DH) in plastic tubs, or single-housed (SH) in hanging wire cages for 12 weeks. Microdialysis in the NAC showed greater sulpiride-induced DA increases in the NAC of SH vs. DH rats, with no difference in basal levels. The data indicate that housing conditions can alter DA D(2) receptor function in the NAC.

A novel, thermostable adaptation of the coupled-enzyme assay for monitoring glucose concentrations was developed for an optimal temperature of 85 degrees C. This is the first report of a thermostable glucostat from a marine hyperthermophile. The continuous assay, using glucokinase (Glk) and glucose-6-phosphate dehydrogenase (Gpd) from Thermotoga maritima, demonstrated robust activity over a range of temperatures (75-90 degrees C) and pH values (6.8- 8.5). Purified glucokinase had a monomeric molecular mass of 33.8kDa while that of glucose-6-phosphate dehydrogenase (D-glucose 6-phosphate:NADP oxidoreductase) was 57.5kDa. The high-temperature assay provided a method for directly assaying the activity of another hyperthermophilic enzyme, 1,4-beta-D-glucan glucohydrolase (GghA) from Thermotoga neapolitana. To provide a benchmark for protein-engineering experiments involving GghA, a three-enzyme continuous assay (performed at 85 degrees C), linking wild-type GghA, Glk, and Gpd, measured glucose produced from GghA's hydrolysis of cellobiose, one of GghA's secondary substrates. The assay established the kinetic behavior of wild-type GghA toward cellobiose and was used to screen for changes in the catalytic efficiency of variant GghA(s) induced by random mutagenesis. The assay's development will allow high-throughput screening of other thermostable glucose-producing enzymes, including those applicable to commercial biomass conversion.

Considerable progress has been made toward understanding the function of the primate rhinal cortex, comprising the entorhinal (ErC) and perirhinal (PrC) cortices. However, translating animal models to human memory has been limited by the technological problems associated with characterizing neural structures in vivo. Functional correlates of hippocampal and rhinal cortex volume changes were examined in a sample of 61 temporal lobe epilepsy patients with mesial temporal sclerosis (MTS; 33 left, 28 right). Patients were administered the Wechsler Adult Intelligence Scale (revised or third edition), the Wechsler Memory Scale (revised or third edition), and a spatial maze task. Neuropsychological data, together with rhinal cortex and hippocampal volumes, collected in our earlier study (O'Brien CE, Bowden SC, Whelan G, Cook MJ, unpublished observations), were analyzed using multiple regression. The only significant predictor of verbal memory function was the difference score between the volume of left hippocampus and the left PrC. Spatial maze scores were predicted by the bilateral sum of ErC volume. The difference score between the left hippocampus and left PrC volumes was the most powerful predictor of verbal episodic memory. Right hippocampal volume was not a significant predictor of nonverbal episodic memory. Verbal and nonverbal semantic memory were not significantly predicted by any combination of rhinal cortex structures. This quantitative study suggests a lateralized or material-specific memory function for the left hippocampus and left PrC, in contrast to the bilateral role of the ErC. The left hippocampus and left PrC appear to act on verbal memory function through an opposing relationship. Finally, differentiation between hippocampal and subhippocampal components in terms of episodic and semantic memory, respectively, could not be supported by the current data.

Familial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.

When two different forms of phosphoenolpyruvate carboxylase (PEPC) from maize (Zea mays L.) leaves are present in an assay it is possible to estimate the ratio of Vmax to Km (V/K) for the two forms separately. This measure of the binding of the substrate by the enzyme permits evaluation of the effects of various treatments on the relative substrate-binding velocity of the enzyme. PEPC diluted 1/20 is present in a mixture of a tetrameric form with a high affinity for phosphoenolpyruvate and a dimeric form with a low affinity (M.-X. Wu, C.R. Meyer, K.O. Willeford, R.T. Wedding [1990] Arch Biochem Biophys 281: 324-329). Malate at 5 mM reduced (V/K)1,[mdash]the V/K of the probable tetrameric form[mdash]almost to zero, but reduced (V/K)2[mdash]the V/K of the probable dimer[mdash]by only about 80%. Glucose-6-phosphate (Glc-6-P) at 5 mM increased (V/K)1 to 155% of the control but had no effect on (V/K)2. Glycerol (20%) alone increased both V/Ks, and its effects are additive to the Glc-6-P effects, implying different mechanisms for activation by Glc-6-P and glycerol.