bluuebunny/crossref_metadata_2025 huggingface dataset:
Residue Depletion of Tritium-Labeled Ivermectin in the Muscle Tissues of Aquacultured Atlantic Salmon, Tilapia, and Catfish following Oral Treatment
Authors: Shaikh Badar , Rummel Nathan , Gieseker Charles , Cheely Christie-Sue , Reimschuessel Renate
Published: January 2012

The residue depletion and metabolism profiles of tritium-labeled ivermectin in the muscle tissues of aquacultured Atlantic salmon Salmo salar, hybrid tilapia (Nile tilapia Oreochromis niloticus × Mozambique tilapia O. mossambicus; hereafter, “tilapia”) and channel catfish Ictalurus punctatus following oral treatment are reported. Fish were administered 3H-ivermectin at the dose level of 0.1 mg/kg of body weight (9–10 μ curies [Ci]) in a gel capsule via a stomach tube. At each postdose withdrawal time (1, 7, 14, 21, and 28 d), six fish of each species were sedated, euthanized, bled, and scaled, and fillets with adhering skin (except for catfish) were collected. The muscle fillets were homogenized in dry ice and an aliquot of each was extracted in acetonitrile followed by a high-performance liquid chromatographic analysis to determine the presence of parent ivermectin and its potential metabolites. The analysis of the muscle extracts revealed that the parent 3H-ivermectin is the major residue present for the three fish species studied. The results showed that the highest radioactive residue concentrations (ivermectin equivalents) of 21 and 6 ng/g were obtained on postdose day 1 for channel catfish and tilapia, respectively. For Atlantic salmon, the highest concentration of 14 ng/g was detected on day 7. By postdose day 21, the ivermectin radioactive residue depleted to less than 10 ng/g for all three species. No significant radioactive residue concentrations of metabolites were detected on any of the sampling days. These results suggest that parent ivermectin could serve as a marker residue to monitor its unauthorized use in Atlantic salmon, tilapia, and channel catfish.
The Principal Principle and Theories of Chance: Another Bug?
Authors: Haddock Joshua
Published: January 2012

Objective chance, or the “big bad bug” of David Lewis's account of Humean Supervenience forces, as is well known, is a modification of the Principal Principle. Here, I argue that standard assumptions regarding conditional probabilities entail several puzzling consequences for Lewis's New Principle, namely, an apparent requirement to account for the chance of a theory of chance. These problems, I argue, cannot be adequately answered within the received framework, and so I suggest that an interpretation of conditional probabilities in terms of Alan Hájek's recent work might go some distance toward their resolution.
Learning to be confident and capable journal reviewers: an Australian perspective
Authors: LU Yanping
Published: December 2011

Journal peer review has been the subject of much research. However, the learning process through which reviewers acquire their reviewing ability, and reviewers' own perceptions of their capability have rarely been a focus. This interview study asked three questions about reviewer capability and training. At what stage did you gain confidence in reviewing? How did you learn how to review? Is formal training necessary? The interview is part of a mixed‐method project studying experienced Australian reviewers. The respondents indicate that learning to review is a continuous cycle in which formal training will not work. Following a mostly self‐guided initiation, new reviewers establish personal reviewing patterns. By trial and error, the patterns are consolidated and the reviewers eventually feel ‘confident’. ‘Decisiveness' is a good sign of becoming confident. Most respondents emphasized that journals could play a crucial role in producing good reviewers, e.g. by specifying unambiguously their expectations of ‘good reviews’.
Book Reviews
Authors: OKERSON Ann
Published: December 2011

Weaving Libraries into the Web: OCLC 1998–2008 Jay Jordan (ed) Routledge, 2010, 226pp. ISBN 978‐0‐41557‐690‐1, hbk, £71.25
The proliferation rate paradox in antimitotic chemotherapy
Authors: Mitchison Timothy J.
Published: December 2011

Cytotoxic cancer chemotherapy drugs are believed to gain selectivity by targeting cells that proliferate rapidly. However, the proliferation rate is low in many chemosensitive human cancers, and it is not clear how a drug that only kills dividing cells could promote tumor regression. Four potential solutions to this “proliferation rate paradox” are discussed for the microtubule-stabilizing drug paclitaxel: drug retention in tumors, killing of quiescent cells, targeting of noncancer cells in the tumor, and bystander effects. Testing these potential mechanisms of drug action will facilitate rational improvement of antimitotic chemotherapy and perhaps cytotoxic chemotherapy more generally.
Single-molecule imaging of translational output from individual RNA granules in neurons
Authors: Tatavarty Vedakumar , Ifrim Marius F. , Levin Mikhail , Korza George , Barbarese Elisa , Yu Ji , Carson John H.
Published: January 2012

Dendritic RNAs are localized and translated in RNA granules. Here we use single-molecule imaging to count the number of RNA molecules in each granule and to record translation output from each granule using Venus fluorescent protein as a reporter. For RNAs encoding activity-regulated cytoskeletal-associated protein (ARC) or fragile X mental retardation protein (FMRP), translation events are spatially clustered near individual granules, and translational output from individual granules is either sporadic or bursty. The probability of bursty translation is greater for Venus-FMRP RNA than for Venus-ARC RNA and is increased in Fmr1-knockout neurons compared to wild-type neurons. Dihydroxyphenylglycine (DHPG) increases the rate of sporadic translation and decreases bursty translation for Venus-FMRP and Venus-ARC RNAs. Single-molecule imaging of translation in individual granules provides new insight into molecular, spatial, and temporal regulation of translation in granules.
Actin retrograde flow and actomyosin II arc contraction drive receptor cluster dynamics at the immunological synapse in Jurkat T cells
Authors: Yi Jason , Wu Xufeng S. , Crites Travis , Hammer John A.
Published: January 2012

Actin retrograde flow and actomyosin II contraction have both been implicated in the inward movement of T cell receptor (TCR) microclusters and immunological synapse formation, but no study has integrated and quantified their relative contributions. Using Jurkat T cells expressing fluorescent myosin IIA heavy chain and F-tractin—a novel reporter for F-actin—we now provide direct evidence that the distal supramolecular activation cluster (dSMAC) and peripheral supramolecular activation cluster (pSMAC) correspond to lamellipodial (LP) and lamellar (LM) actin networks, respectively, as hypothesized previously. Our images reveal concentric and contracting actomyosin II arcs/rings at the LM/pSMAC. Moreover, the speeds of centripetally moving TCR microclusters correspond very closely to the rates of actin retrograde flow in the LP/dSMAC and actomyosin II arc contraction in the LM/pSMAC. Using cytochalasin D and jasplakinolide to selectively inhibit actin retrograde flow in the LP/dSMAC and blebbistatin to selectively inhibit actomyosin II arc contraction in the LM/pSMAC, we demonstrate that both forces are required for centripetal TCR microcluster transport. Finally, we show that leukocyte function–associated antigen 1 clusters accumulate over time at the inner aspect of the LM/pSMAC and that this accumulation depends on actomyosin II contraction. Thus actin retrograde flow and actomyosin II arc contraction coordinately drive receptor cluster dynamics at the immunological synapse.
Remote Ischemic Preconditioning Applied during Isoflurane Inhalation Provides No Benefit to the Myocardium of Patients Undergoing On-pump Coronary Artery Bypass Graft Surgery
Authors: Lucchinetti Eliana , Bestmann Lukas , Feng Jianhua , Freidank Heike , Clanachan Alexander S. , Finegan Barry A. , Zaugg Michael
Published: January 2012

Background

Two preconditioning stimuli should induce a more consistent overall cell protection. We hypothesized that remote ischemic preconditioning (RIPC, second preconditioning stimulus) applied during isoflurane inhalation (first preconditioning stimulus) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting.

Methods

In this placebo-controlled randomized controlled study, patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping. Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance. The primary outcome was high-sensitivity cardiac troponin T release. Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide, high-sensitivity C-reactive protein, S100 protein, and short- and long-term clinical outcomes. Gene expression profiles were obtained from atrial tissue using microarrays.

Results

RIPC (n = 27) did not reduce high-sensitivity cardiac troponin T release when compared with placebo (n = 28). Likewise, N-terminal pro-brain natriuretic peptide, a marker of myocardial dysfunction; high-sensitivity C-reactive protein, a marker of perioperative inflammatory response; and S100, a marker of cerebral injury, were not different between the groups. The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infarctions was higher in the RIPC group than the placebo group (14/27 vs. 6/28, P = 0.036). However, there was no difference in the 6-month cardiovascular outcome. N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism (P = 0.001) and DNA-damage signaling (P < 0.001), but not with RIPC-induced changes in gene expression.

Conclusions

RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting.
Effects of Regional and Whole-body Hypothermic Treatment before and after Median Nerve Injury on Neuropathic Pain and Glial Activation in Rat Cuneate Nucleus
Authors: Tsai Yi-Ju , Huang Chun-Ta , Lin Shih-Chang , Yeh Jiann-Horng
Published: January 2012

Background

Neuroprotective effects of hypothermia on peripheral nerve injury remain uncertain. This study investigated the efficacy of hypothermia in attenuating neuropathic pain and glial activation in the cuneate nucleus in a median nerve chronic constriction injury (CCI) model.

Methods

Sprague-Dawley rats (n = 246) that underwent median nerve ligature at the elbow received various degrees of regional and whole-body hypothermia 15 min before CCI and 5 h, 1, 3, and 5 days after CCI. Hypothermia was maintained for 4 h. Seven days after CCI, behavioral and electrophysiological testings were conducted. Immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analysis of glial activation and measuring pro-inflammatory cytokines, respectively.

Results

Mild (32°C) and deep (28°C) regional hypothermia administered preinjury and 5 h postinjury attenuated neuropathic pain and glial activation. Application of whole-body hypothermia preinjury and 5 h postinjury provided a similar therapeutic effect. However, whole-body hypothermia, but not regional hypothermia, applied 1, 3, and 5 days postinjury attenuated glial activation and neuropathic pain. Similarly, on days 1, 3, and 5 postinjury, only whole-body hypothermia was effective in decreasing proinflammatory cytokine levels. The increase in injury discharge observed after CCI could be suppressed by regional or whole-body hypothermia at different stages of nerve injury.

Conclusions

At the early stage following nerve injury, regional and whole-body hypothermia suppresses ectopic discharges, and consequently inhibits glial activation and neuropathic pain. At the later stage, pain processing is mediated mainly by cytokines released from activated microglia; therefore, only whole-body hypothermia is effective in modulating pain.
First Human Administration of MR04A3
Authors: Sneyd J. Robert , Rigby-Jones Ann E. , Cross Maurice , Tominaga Hideharu , Shimizu Satoshi , Ohkura Takako , Grimsehl Karen
Published: January 2012

Background

JM-1232(-), (-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta [f]isoindol-1(2H)-one, molecular formula, C(24)H(27)N(3)O(2); molecular weight, 389.49, is a novel isoindoline water-soluble benzodiazepine receptor agonist with favorable anesthetic/sedative properties in animals. MR04A3 is a 1% aqueous presentation of JM-1232(-).

Methods

In Step 1, healthy male volunteers received 10-min infusions of MR04A3, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg, with three MR04A3 subjects and one placebo subject per dose concentration. In Step 2, doses were 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, and 0.4 mg/kg over 1 min with six MR04A3 subjects and one placebo subject per dose concentration.

Results

Hypnotic effects of MR04A3 were seen at all dose concentrations in Step 1 and at doses of 0.075 mg/kg or more in Step 2. Central nervous system effect was seen at all dose concentrations with larger doses of MR04A3 producing a deeper and longer reduction in bispectral index. Ramsay sedation scores were increased with higher doses causing sedation and then unresponsiveness. The adverse event profile of subjects receiving MR04A3 was similar to that of subjects given placebo except that some subjects receiving MR04A3 developed upper airway obstruction while sedated. This responded to simple maneuvers (i.e., chin lift). Changes in systolic arterial blood pressure and heart rate were minimal.

Conclusions

MR04A3 is hypnotic in man with a satisfactory hemodynamic and safety profile.
Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract
Authors: Garg M. , Angus P. W. , Burrell L. M. , Herath C. , Gibson P. R. , Lubel J. S.
Published: January 2012

Background

The renin‐angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues.

Aim

To elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract.

Methods

An extensive online literature review including Pubmed and Medline.

Results

There is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases.

Conclusions

The gastrointestinal renin‐angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches.
A comparison of traditional vs. Canadian tailored prophylaxis dosing of prophylactic factor infusions in children with haemophilia A and B in a single hemophilia treatment center
Authors: DODD C. , WATTS R. G.
Published: January 2012

Summary.  Prophylactic infusion of clotting factor concentrates is a developing standard of care for individuals with haemophilia. The ideal schedule and techniques of prophylactic infusions remain incompletely defined. Our aim was to determine the optimal techniques and schedules for factor prophylaxis in paediatric patients. A retrospective electronic medical record review of all children treated with prophylactic factor infusions in a single Haemophilia Treatment Center was conducted. Comparison of traditional vs. Canadian dosing regimens and primary vs. secondary prophylaxis was made. Failure of prophylaxis was defined as the first serious bleed. A total of 58 children were identified for review. Five cases were excluded (four due to high titre inhibitors and one due to repeated non‐compliance), thus there were 53 total cases: 46 with severe haemophilia, 2 with moderate haemophilia, 5 with mild haemophilia, 44 with haemophilia A and 9 with haemophilia B; 32 Traditional dosing and 21 Canadian dosing regimens. Patients on primary prophylaxis had a decreased failure rate (25%) compared to children treated with secondary prophylaxis (67%) regardless of technique of prophylaxis. When compared to a ‘Traditional’ factor prophylaxis schedule, the ‘Canadian’ tailored prophylaxis protocol was comparable with the exception of a decreased use of implanted venous devices in the ‘Canadian’ group. Ongoing bleeding (primarily joint bleeds) occurs with all prophylactic regimens. The lowest incidence of treatment failure was noted in children who began primary prophylaxis at a young age and before initial joint bleeds. Primary prophylaxis is superior to secondary prophylaxis regardless of dosing regimen. Traditional and Canadian dosing regimens were equivalent in outcome when measured over several years of follow‐up.
Imbalance between endothelial injury and repair in patients with polymyalgia rheumatica: improvement with corticosteroid treatment
Authors: Pirro M. , Bocci E. B. , Di Filippo F. , Schillaci G. , Mannarino M. R. , Bagaglia F. , Gerli R. , Mannarino E.
Published: December 2011

Abstract.  Pirro M, Bocci EB, Di Filippo F, Schillaci G, Mannarino MR, Bagaglia F, Gerli R, Mannarino E (From the Unit of Internal Medicine, Angiology and Arteriosclerosis, Department of Clinical and Experimental Medicine; Division of Rheumatology, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy). Imbalance between endothelial injury and repair in patients with polymyalgia rheumatica: improvement with corticosteroid treatment. J Intern Med 2012; 272: 177–184.

Objectives.  Polymyalgia rheumatica (PMR) is a rheumatic disease that is characterized by intense activation of systemic inflammation. Systemic inflammation has been associated with an imbalance between endothelial injury and repair, defined by an increased number of circulating endothelial microparticles (EMPs) and a reduced number of endothelial progenitor cells (EPCs). We investigated the association between inflammation and endothelial injury and repair in patients with PMR and evaluated the effects of corticosteroid therapy on EMP and EPC levels.

Design, setting and subjects.  We conducted a case–control study in 34 patients with never‐treated active PMR and 34 healthy age‐ and sex‐matched controls. Patients with PMR participated in a 1‐month intervention open‐label study with corticosteroid therapy. Circulating EMPs (CD31+/CD42−) and EPCs (CD34+/KDR+) were quantified by fluorescence‐activated cell sorting analysis.

Results.  Patients with PMR had an increased EMP/EPC ratio compared with controls [median (IQR): 6.5 (3.0–11.5) vs. 1.1 (0.7–1.5), P < 0.001], because of both increased EMP and reduced EPC levels. Levels of C‐reactive protein (CRP) were associated with an increased EMP/EPC ratio (β = 0.48, P = 0.001), irrespective of traditional cardiovascular risk factors. Corticosteroid therapy led to a significant CRP reduction [from 3.9 (1.5–6.7) to 0.6 (0.2–1.2) mg dL−1, P < 0.05], paralleled by a consistent 81% decline in the EMP/EPC ratio. CRP and EMP/EPC ratio reductions were significantly correlated (rho = 0.37, P = 0.04).

Conclusions.  Polymyalgia rheumatica is associated with a significant imbalance between endothelial injury and repair, which is dependent on the degree of systemic inflammation. Attenuation of inflammation by short‐term corticosteroid therapy might have a role in limiting endothelial fragmentation and promote endothelial repair.
Societal participation: examining the impact of a rehabilitation approach for young people with schizophrenia
Authors: VAN WEL T. F. , LANDSHEER J. A.
Published: December 2011

Accessible summary

In addition to medical and psychosocial treatment of impairments, societal participation should be recognized as an important treatment goal for patients with schizophrenia, and it can be applied in daily practice by nurses and social workers, even when psychiatric impairments require acute care.

Our research indicated that rehabilitation counselling by nurses and social workers within a multidisciplinary team helps to increase the societal participation level of young people with schizophrenia, while their impairments scores remained stable.

Patients with more mild impairments seemed to profit more from rehabilitation counselling while patients whose impairments were more severe seemed to profit less. Our research also indicated that patients with similar levels of impairment did not show differences in their level of societal participation, regardless of drug use.

Drug use as such is not a contraindication for rehabilitation counselling. Treatment of impairments, including management of drug addiction, should be closely interwoven with support for a patient's rehabilitation goals.

This paper is based on research that focuses on the impact of a rehabilitation approach with respect to 99 young people diagnosed with schizophrenia in a Dutch mental health facility. The approach focused on societal participation goals. Nurses and social workers play a key role in such treatment. The research focused on developmental trajectories and showed significant improvement with respect to societal participation levels. Impairment scores remained stable. The results indicate that rehabilitation counselling by nurses and social workers, in addition to medication and psychosocial treatment and integrated in a multidisciplinary team, can make a difference in a patient's societal participation.
Risk factor analysis of hepatitis C virus infection among Chinese blood donors in Hong Kong
Authors: Wong H. K. , Lee C. K. , Leung J. N. S. , Tsoi W. C. , Lin C. K.
Published: December 2011

Background: Hepatitis C virus (HCV) infection can result in serious hepatic complications and hence potentially significant burden to the society. Despite advances in technology, transfusion‐transmitted HCV infection still exists. To further minimise the risk, a review on the epidemiology of HCV infection among Chinese blood donors in Hong Kong was conducted.

Methods: All donations associated with HCV infection confirmed by positive serologic diagnosis with or without molecular confirmation during the period from 2003 to 2010 were studied. Demographic data were retrieved and risk factors were identified.

Results: HCV infection was more commonly seen in first time donors and donors with blood transfusion history before the availability of HCV testing, whereas its association with intravenous drug use was noted to be decreasing. Interestingly, half of the HCV positive donors in 2008–2010 were young donors aged below 21, which was also the group with the highest rate of no known source of infection.

Conclusion: A subgroup of younger age donors was found to have no known risk factor. To develop better screening strategy, it is recommended that a more detailed analysis of this group of donors is required.
MHC Class II is an Important Genetic Risk Factor for Canine Systemic Lupus Erythematosus (SLE)‐Related Disease: Implications for Reproductive Success
Authors: Wilbe M , Andersson G
Published: December 2011

Contents

Major histocompatibility complex (MHC) class II genes are important genetic risk factors for development of immune‐mediated diseases in mammals. Recently, the dog (Canis lupus familiaris) has emerged as a useful model organism to identify critical MHC class II genotypes that contribute to development of these diseases. Therefore, a study aimed to evaluate a potential genetic association between the dog leukocyte antigen (DLA) class II region and an immune‐mediated disease complex in dogs of the Nova Scotia duck tolling retriever breed was performed. We show that DLA is one of several genetic risk factors for this disease complex and that homozygosity of the risk haplotype is disadvantageous. Importantly, the disease is complex and has many genetic risk factors and therefore we cannot provide recommendations for breeders exclusively on the basis of genetic testing for DLA class II genotype.
Investigation on Association and Expression of ESR2 as a Candidate Gene for Boar Sperm Quality and Fertility
Authors: Gunawan A , Cinar MU , Uddin MJ , Kaewmala K , Tesfaye D , Phatsara C , Tholen E , Looft C , Schellander K
Published: December 2011

Contents

ESR2 is involved in oestrogen‐related apoptosis in cell cycle spermatogenesis but their effects have not yet confirmed in pig. Therefore, this study was aimed to investigate the association of ESR2 polymorphism with sperm quality and boar fertility traits and to analyse the ESR2 mRNA and protein expressions in boar reproductive tissues. DNA samples from 203 Pietrain (PI) and 100 Pietrain × Hampshire (PIHA) pigs with records of sperm quality [sperm concentration (SCON), motility (MOT), semen volume (VOL), plasma droplet rate (PDR) and abnormal spermatozoa rate (ASR)] and fertility [non‐return rate (NRR) and number of piglet born alive (NBA)] traits were available. A SNP in coding region of ESR2 g.35547A>G in exon 5 was associated with MOT and PDR in the PI and with SCON, VOL, MOT and PDR in PIHA population. For mRNA and protein expression study, a total of six boars were divided into two groups with group I (G‐I) and group II (G‐II) where G‐I characterized for relatively a better sperm quality according to the mean of two groups. mRNA expression was higher in brain and testis than that in all parts of epididymis. Both qRT‐PCR and western blot analysis revealed that the ESR2 gene expression and protein expression were significantly higher in testis collected from G‐II compared with that of G‐I boars. Moreover, ESR2 protein localization in germ cell, Leydig and Sertoli cells, epithelial cells and spermatozoa was remarkable, which indicated the important role of ESR2 in spermatogenesis process. These results might shed new light on the roles of ESR2 in spermatogenesis as candidate for boar fertility, but still the lack of association across populations should be considered.
Incursion preparedness: anticipating the arrival of an economically important plant pathogen Xylella fastidiosa Wells (Proteobacteria: Xanthomonadaceae) and the insect vector Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae) in Australia
Authors: Rathé Anna A , Pilkington Leigh J , Gurr Geoff M , Hoddle Mark S , Daugherty Matthew P , Constable Fiona E , Luck Joanne E , Powell Kevin S , Fletcher Murray J , Edwards Owain R
Published: December 2011

The glassy‐winged sharpshooter, Homalodisca vitripennis (Germar) (Hemiptera: Cicadellidae), is an important insect vector of the xylem‐limited plant pathogen Xylella fastidiosa Wells et al. that causes diseases in numerous plant species including food and feedstock crops, ornamentals and weeds. Both the pathogen and the vector are native to the Americas, and H. vitripennis has demonstrated high invasive ability but to date neither has been detected in Australia. The Australian wine grape, table grape, peach, plum, nectarine and citrus industries are particularly concerned about the arrival of X. fastidiosa and H. vitripennis because of the potential economic impact on these important commodities. Other commodity producers in Australia should also be concerned about this vector‐pathogen, in particular the ornamental plant, avocado and olive industries. Past interceptions of H. vitripennis and the potential for X. fastidiosa to be moved in live plant material or within live vectors indicate the need for rapid detection of an incursion in areas considered at high risk. This requires identification of regions that have climatic and environmental conditions conducive to X. fastidiosa and H. vitripennis establishment as well as a detailed knowledge of their respective potential host plant ranges in new areas. These climatic regions and host plant species can then be targeted for monitoring in order to detect an incursion at an early stage. CLIMEX modelling has shown that much of coastal Australia has temperatures suitable for survival of both the vector and pathogen. A range of other requirements in addition to suitable climate must, however, be satisfied for an incursion to lead to establishment, proliferation and spread. This review article provides information that shows that the Australian environment is suitable for the establishment of H. vitripennis and that Australian native plant species are likely to serve as X. fastidiosa hosts and subsequent pathogen sources, and highlights future research directions.
Canagliflozin improves glycaemic control over 28 days in subjects with type 2 diabetes not optimally controlled on insulin
Authors: Devineni D. , Morrow L. , Hompesch M. , Skee D. , Vandebosch A. , Murphy J. , Ways K. , Schwartz S.
Published: January 2012

Aim: Canagliflozin is a sodium‐glucose co‐transporter 2 (SGLT2) inhibitor that is being investigated for the treatment of type 2 diabetes mellitus (T2DM).

Methods: This was a randomized, double‐blind, placebo‐controlled, parallel‐group, 28‐day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent. Subjects were treated with canagliflozin 100 mg QD or 300 mg twice daily (BID) or placebo. Safety, tolerability, pharmacokinetic characteristics and pharmacodynamic effects of canagliflozin were examined. Glucose malabsorption following a 75‐g oral glucose challenge was also examined.

Results: Canagliflozin pharmacokinetics were dose‐dependent, and the elimination half‐life ranged from 12 to 15 h. After 28 days, the renal threshold for glucose excretion was reduced; urinary glucose excretion was increased; and A1C, fasting plasma glucose and body weight decreased in subjects administered canagliflozin (A1C reductions: 0.19% with placebo, 0.73% with 100 mg QD, 0.92% with 300 mg BID; body weight changes: 0.03 kg increase with placebo, 0.73 kg reduction with 100 mg QD, 1.19 kg reduction with 300 mg BID). Glucose malabsorption was not observed with canagliflozin treatment. There were no deaths, serious adverse events or severe hypoglycaemic episodes. The incidence of adverse events was similar across groups. There were no clinically meaningful changes in routine laboratory safety tests, vital signs or electrocardiograms.

Conclusion: In subjects receiving insulin and oral antihyperglycaemic therapy, canagliflozin was well tolerated without evidence for glucose malabsorption, had pharmacokinetic characteristics consistent with once‐daily dosing, and improved glycaemic control.
Efficacy and safety of suberoylanilide hydroxamic acid (Vorinostat) in the treatment of canine corneal fibrosis
Authors: Bosiack Ann P. , Giuliano Elizabeth A. , Gupta Rangan , Mohan Rajiv R.
Published: December 2011

Objective  Study aims were to evaluate the safety and efficacy of the Food and Drug Administration‐approved drug Vorinostat [suberoylanilide hydroxamic acid (SAHA)] in the treatment of canine corneal fibrosis using an in vitro model.

Methods  Healthy donor canine corneas were collected and used to generate primary canine corneal fibroblasts (CCFs) by growing cultures in minimal essential medium supplemented with 10% fetal bovine serum. Canine corneal myofibroblasts, used as a model for corneal fibrosis, were produced by growing CCF cultures in serum‐free medium containing transforming growth factor β1 (1 ng/mL). Trypan blue exclusion assays were used to determine the optimal SAHA dose for this in vitro model. Four hour after culturing with TGFβ1, CCF cultures were treated with 0.06% SAHA for 5 min (group 1) and for 24 h (group 2), representing single and multiple dose treatment regimes, respectively. Cultures were then further incubated in the presence of TGFβ1 (1 ng/μL) under serum‐free conditions until they reached 70% confluence. Trypan blue exclusion, immunocytochemistry, and TUNEL assays were used to evaluate the cytotoxicity of SAHA. Real‐time PCR, western blot analysis, and immunocytochemistry were used to determine the efficacy of SAHA to inhibit canine corneal myofibroblast formation.

Results  Topical SAHA application in both treatment groups successfully decreased α‐smooth muscle actin expression when compared to the TGFβ1 only treatment group (P < 0.05). Tested SAHA did not affect CCF phenotype or cellular viability and did not cause significant cell death.

Conclusions  Suberoylanilide hydroxamic acid safely and effectively inhibits TGFβ1‐induced CCFs transformation to myofibroblast in vitro.
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs – part I: clinical signs, histopathology, and inheritance
Authors: Hartley Claudia , Donaldson David , Smith Ken C. , Henley William , Lewis Tom W. , Blott Sarah , Mellersh Cathryn , Barnett Keith C.
Published: December 2011

The clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long‐term follow‐up of cases (13/25) is described. Immunomodulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode.
Cultured fish: integrative biology and management of domestication and interactions with wild fish
Authors: Lorenzen Kai , Beveridge Malcolm C.M. , Mangel Marc
Published: January 2012

Fish aquaculture for commodity production, fisheries enhancement and conservation is expanding rapidly, with many cultured species undergoing inadvertent or controlled domestication. Cultured fish are frequently released, accidentally and deliberately, into natural environments where they may survive well and impact on wild fish populations through ecological, genetic, and technical interactions. Impacts of fish released accidentally or for fisheries enhancement tend to be negative for the wild populations involved, particularly where wild populations are small, and/or highly adapted to local conditions, and/or declining. Captive breeding and supplementation can play a positive role in restoring threatened populations, but the biology of threatened populations and the potential of culture approaches for conserving them remain poorly understood. Approaches to the management of domestication and cultured‐wild fish interactions are often ad hoc, fragmented and poorly informed by current science. We develop an integrative biological framework for understanding and managing domestication and cultured‐wild fish interactions. The framework sets out how management practices in culture and for cultured fish in natural environments affect domestication processes, interactions between cultured and wild fish, and outcomes in terms of commodity production, fisheries yield, and conservation. We also develop a typology of management systems (specific combinations of management practices in culture and in natural environments) that are likely to provide positive outcomes for particular management objectives and situations. We close by setting out avenues for further research that will simultaneously improve fish domestication and management of cultured‐wild fish interactions and provide key insights into fundamental biology.
Obovatol improves cognitive functions in animal models for Alzheimer’s disease
Authors: Choi Dong‐Young , Lee Jae Woong , Peng Jin , Lee Young Jung , Han Jin‐Yi , Lee Yeon Hee , Choi Im Seop , Han Sang Bae , Jung Jae Kyung , Lee Woong Soo , Lee Seung‐Ho , Kwon Byoung‐Mog , Oh Ki‐Wan , Hong Jin Tae
Published: December 2011

J. Neurochem. (2012) 120, 1048–1059.

Etiology of Alzheimer’s disease (AD) is obscure, but neuroinflammation and accumulation of β‐amyloid (Aβ) are implicated in pathogenesis of AD. We have shown anti‐inflammatory and neurotrophic properties of obovatol, a biphenolic compound isolated from Magnolia obovata. In this study, we examined the effect of obovatol on cognitive deficits in two separate AD models: (i) mice that received intracerebroventricular (i.c.v.) infusion of Aβ1–42 (2.0 μg/mouse) and (ii) Tg2576 mice‐expressing mutant human amyloid precursor protein (K670N, M671L). Injection of Aβ1–42 into lateral ventricle caused memory impairments in the Morris water maze and passive avoidance tasks, being associated with neuroinflammation. Aβ1–42‐induced abnormality was significantly attenuated by administration of obovatol. When we analyzed with Tg2576 mice, long‐term treatment of obovatol (1 mg/kg/day for 3 months) significantly improved cognitive function. In parallel with the improvement, treatment suppressed astroglial activation, BACE1 expression and NF‐κB activity in the transgenic mice. Furthermore, obovatol potently inhibited fibrillation of Aβin vitro in a dose‐dependent manner, as determined by Thioflavin T fluorescence and electron microscopic analysis. In conclusion, our data demonstrated that obovatol prevented memory impairments in experimental AD models, which could be attributable to amelioration of neuroinflammation and amyloidogenesis by inhibition of NF‐κB signaling pathway and anti‐fibrillogenic activity of obovatol.
Fear of a foreign railroad: transnationalism, trainspace, and (im)mobility in the Chicago suburbs
Authors: Cidell Julie
Published: December 2011

The fluidity and mobility of the twenty‐first century are grounded in physical infrastructure such as airports and train stations but also on the routes along which people and goods travel. Within recent work on the meanings, practices and experiences of flying, driving, walking, cycling or riding the rails, the focus has been on the travel of people rather than commodities and on network nodes rather than routes. Nevertheless, the transport of freight and its interaction with people and places along distribution routes has significant implications for understanding discursive constructions of the national and the foreign. In 2007, the Canadian National railroad began the process of purchasing a beltline railroad around Chicago to ease the passage of containerised freight from Asia to North American distribution centres. Suburban communities protested the transaction, arguing that the increase in trains would lead to traffic congestion, problems with emergency vehicle access and water supply contamination. Despite the local scale of these concerns, opponents framed their protest in terms of aforeignrailroad disruptingAmericancommunities, suggesting deeper underlying concerns about the transnational nature of the transaction and the resulting route. They also argued for considering the spaces of this mode of transportation, what I term trainspace, as consisting of more than the vehicles, infrastructure and adjacent properties, underlining the importance of considering routes and infrastructure as a fundamental social component of transnational processes and of considering motility or potential movement along with mobility.
Basal Cell Carcinoma in Childhood: A Case Report
Authors: Zoccali Giovanni , Pajand Reza , Giuliani Maurizio
Published: December 2011

Abstract:  Basal cell carcinoma is the most common tumor of skin. Its incidence increases with age, although it is relatively infrequent under the age of 50 years, and its occurrence in childhood is exceedingly rare. This article describes an otherwise typical basal cell carcinoma arising in young patient, with emphasis on histologic diagnosis.
Irritant Contact Dermatitis Due to Ammonium Bifluoride in Two Infant Twins
Authors: Toledo Fernando , Silvestre Juan Francisco , Cuesta Laura , Bañuls José
Published: December 2011

Abstract:  Ammonium bifluoride is one of the most corrosive acids that may produce severe chemical burns when in contact with skin. This hazardous chemical is widely used in household products. We report two pediatric cases of irritant contact dermatitis after exposure to a rust remover, which contained ammonium bifluoride.
Clinical genetic studies in benign childhood epilepsy with centrotemporal spikes
Authors: Vears Danya F. , Tsai Meng‐Han , Sadleir Lynette G. , Grinton Bronwyn E. , Lillywhite Leasha M. , Carney Patrick W. , Simon Harvey A. , Berkovic Samuel F. , Scheffer Ingrid E.
Published: January 2012

Purpose:  To accurately determine the frequency and nature of the family history of seizures in patients with benign childhood epilepsy with centrotemporal spikes (BECTS).

Method:  Participants with BECTS were recruited from the electroencephalography (EEG) laboratories of three pediatric centers and by referral. Pedigrees were constructed for up to three degrees of relatedness for each proband. All available affected and unaffected individuals underwent phenotyping using a validated seizure questionnaire. The proportion of affected relatives according to degree of relatedness was calculated and phenotypic patterns were analyzed.

Key Findings:  Fifty‐three probands with BECTS had a mean age of seizure onset at 7.8 years (range 2–12 years). Thirty‐four (64%) of 53 patients were male. For 51 participants, pedigrees were available for three degrees of relatedness. Fifty‐seven (2.7%) of 2,085 relatives had a history of seizures: Twenty‐one (9.8%) of 214 first‐degree, 15 (3%) of 494 second‐degree, and 21 (1.5%) of 1,377 third‐degree relatives. Febrile seizures were the most frequent phenotype, occurring in 26 of 57 affected relatives. There were 34 relatives with epilepsy: 6.5% (14 of 214) first‐degree, 1.8% (9 of 494) second‐degree, and 0.8% (11 of 1,377) third‐degree relatives. Of 21 affected first‐degree relatives: 8 of 21 had febrile seizures (FS), 4 had BECTS, 2 had epilepsy‐aphasia spectrum disorder, one had temporal lobe epilepsy with hippocampal sclerosis, 2 had focal epilepsy of unknown cause, 2 had genetic generalized epilepsies, and 3 had miscellaneous.

Significance:  The frequency of epilepsies in relatives and the heterogeneous syndromes observed suggest that BECTS has a genetic component consistent with complex inheritance. Focal epilepsies are the most common seizure disorder observed in relatives, especially BECTS and epilepsy‐aphasia spectrum disorder. Additional acquired or environmental factors are likely to be necessary for expression of the seizure disorder.
Is major depressive disorder specifically associated with mesial temporal sclerosis?
Authors: Sanchez‐Gistau Vanessa , Sugranyes Gisela , Baillés Eva , Carreño Mar , Donaire Antonio , Bargalló Nuria , Pintor Luis
Published: January 2012

Purpose:  Whether a specific lesion such as mesial temporal sclerosis (MTS) increases the risk for a mood disorder in epilepsy remains subject to debate. Despite evidence of limbic system involvement in the genesis of emotional symptoms, recent studies fail to support an association between depression and MTS. We aimed to clarify this controversial issue by overcoming prior methodologic limitations, hypothesizing that rates of major depressive disorder (MDD) would be higher in patients with MTS.

Methods:  Three hundred eight patients with focal epilepsy (International League Against Epilepsy [ILAE] criteria), were classified into three groups on the basis of neuroimaging findings: MTS, a lesion different from MTS, or absence of lesion. Patients were assessed using the Structured Interview for DSM‐IV axis I psychiatric disorders (SCID‐I), by a psychiatrist blinded to epilepsy subtype. The Spanish version of the Hospital Anxiety and Depression Scale (HADS) was also administered. A complete logistic regression analysis was performed to investigate the association between MTS and MDD.

Key Findings:  MTS increased the likelihood of a lifetime MDD by nearly 2.5. No other current or “postseizure onset” lifetime Axis I DSM‐IV psychiatric disorder was associated with MTS. Female gender, primary education, comorbid anxiety disorders, and antidepressant treatment were also associated with an increased risk of MDD. Marriage was found to be a protective factor for MDD.

Significance:  Our results support a specific association between MTS and lifetime “postseizure onset,” MDD. The lack of association with current depression is in line with the hypothesis that the link between MTS and depression is more of a chronic than a state‐dependent condition.
Osteomyelitis of the Patella in Eight Foals
Authors: Kay Alastair T. , Hunt Robert J. , Rodgerson Dwayne H. , Spirito Michael A. , Santschi Elizabeth M. , Payne Richard J.
Published: January 2012

Objective

To describe the characteristics of osteomyelitis lesions of the patella and to report short‐ and long‐term outcome after treatment in 8 foals.

Study Design

Retrospective case series.

Animals

Foals (n = 8).

Methods

Medical records (2003–2007) and radiographs of foals that had osteomyelitis of the patella were reviewed. Inclusion criteria included clinical, radiographic, and surgical findings consistent with osteomyelitis of the patella, and a long‐term follow‐up of >15 months. Information acquired included signalment, hematologic and serum biochemical profile results, clinical and radiographic signs, surgical technique and perioperative treatment. Follow‐up radiographs were evaluated and outcome was determined from veterinary examination, race records, and telephone questionnaire.

Results

Six foals survived long term (15 months–4 years); all had intralesional and systemic antimicrobial therapy, along with synovial lavage and antimicrobial medication. All were sound and achieved either yearling sales (n=3), show hunter or racing (2). Two foals died in the short term from renal failure and suppurative peritonitis secondary to cecal perforation, 1 remaining lame with suppurative osteonecrosis confirmed at necropsy. This foal was not administered intralesional antimicrobial therapy.

Conclusions

Prompt medical and surgical therapy for osteomyelitis of the patella can result in a good prognosis for soundness and a potential athletic career. Concurrent septicemia or other systemic perinatal disease can result in prolonged therapy and delayed recovery.