Antimicrobial resistance in Antarctica: is it still a pristine environment?

Although the rapid spread of antimicrobial resistance (AMR), particularly in relation to clinical settings, is causing concern in many regions of the globe, remote, extreme environments, such as Antarctica, are thought to be relatively free from the negative impact of human activities. In fact, Antarctica is often perceived as the last pristine continent on Earth. Such remote regions, which are assumed to have very low levels of AMR due to limited human activity, represent potential model environments to understand the mechanisms and interactions underpinning the early stages of evolution, de novo development, acquisition and transmission of AMR. Antarctica, with its defined zones of human colonisation (centred around scientific research stations) and large populations of migratory birds and animals, also has great potential with regard to mapping and understanding the spread of early-stage zoonotic interactions. However, to date, studies of AMR in Antarctica are limited. Here, we survey the current literature focussing on the following: i) Dissection of human-introduced AMR versus naturally occurring AMR, based on the premise that multiple drug resistance and resistance to synthetic antibiotics not yet found in nature are the results of human contamination ii) The potential role of endemic wildlife in AMR spread There is clear evidence for greater concentrations of AMR around research stations, and although data show reverse zoonosis of the characteristic human gut bacteria to endemic wildlife, AMR within birds and seals appears to be very low, albeit on limited samplings. Furthermore, areas where there is little, to no, human activity still appear to be free from anthropogenically introduced AMR. However, a comprehensive assessment of AMR levels in Antarctica is virtually impossible on current data due to the wide variation in reporting standards and methodologies used and poor geographical coverage. Thus, future studies should engage directly with policymakers to promote the implementation of continent-wide AMR reporting standards. The development of such standards alongside a centralised reporting system would provide baseline data to feedback directly into wastewater treatment policies for the Antarctic Treaty Area to help preserve this relatively pristine environment. Video Abstract.

New and emerging pathogens in canine infectious respiratory disease.

Canine infectious respiratory disease is a common, worldwide disease syndrome of multifactorial etiology. This review presents a summary of 6 viruses (canine respiratory coronavirus, canine pneumovirus, canine influenza virus, pantropic canine coronavirus, canine bocavirus, and canine hepacivirus) and 2 bacteria (Streptococcus zooepidemicus and Mycoplasma cynos) that have been associated with respiratory disease in dogs. For some pathogens a causal role is clear, whereas for others, ongoing research aims to uncover their pathogenesis and contribution to this complex syndrome. Etiology, clinical disease, pathogenesis, and epidemiology are described for each pathogen, with an emphasis on recent discoveries or novel findings.

Identification of quantitative trait loci (QTL) for resistance to Fusarium crown rot (Fusarium pseudograminearum) in multiple assay environments in the Pacific Northwestern US.

Fusarium crown rot (FCR), caused by Fusarium pseudograminearum and F. culmorum, reduces wheat (Triticum aestivum L.) yields in the Pacific Northwest (PNW) of the US by as much as 35%. Resistance to FCR has not yet been discovered in currently grown PNW wheat cultivars. Several significant quantitative trait loci (QTL) for FCR resistance have been documented on chromosomes 1A, 1D, 2B, 3B, and 4B in resistant Australian cultivars. Our objective was to identify QTL and tightly linked SSR markers for FCR resistance in the partially resistant Australian spring wheat cultivar Sunco using PNW isolates of F. pseudograminerarum in greenhouse and field based screening nurseries. A second objective was to compare heritabilities of FCR resistance in multiple types of disease assaying environments (seedling, terrace, and field) using multiple disease rating methods. Two recombinant inbred line (RIL) mapping populations were derived from crosses between Sunco and PNW spring wheat cultivars Macon and Otis. The Sunco/Macon population comprised 219 F(6):F(7) lines and the Sunco/Otis population comprised 151 F(5):F(6) lines. Plants were inoculated with a single PNW F. pseudograminearum isolate (006-13) in growth room (seedling), outdoor terrace (adult) and field (adult) assays conducted from 2008 through 2010. Crown and lower stem tissues of seedling and adult plants were rated for disease severity on several different scales, but mainly on a numeric scale from 0 to 10 where 0 = no discoloration and 10 = severe disease. Significant QTL were identified on chromosomes 2B, 3B, 4B, 4D, and 7A with LOD scores ranging from 3 to 22. The most significant and consistent QTL across screening environments was located on chromosome 3BL, inherited from the PNW cultivars Macon and Otis, with maximum LOD scores of 22 and 9 explaining 36 and 23% of the variation, respectively for the Sunco/Macon and Sunco/Otis populations. The SSR markers Xgwm247 and Xgwm299 flank these QTL and are being validated for use in marker-assisted selection for FCR resistance. This is the first report of QTL associated with FCR resistance in the US.

VEGF modulates the effects of gonadotropins in granulosa cells.

Follicle selection is associated with an increase in the expression of vascular endothelial growth factor (VEGF) and its receptors in granulosa cells, however, the roles of VEGF in regulating the function of these or other non-endothelial cells in the ovary have not been explored in detail. The current study used bovine cell cultures to investigate potential roles of VEGF in the regulation of granulosa cell function during follicle development. Granulosa cells were obtained from morphologically healthy follicles 4 to 8 mm or 9 to 14 mm in diameter (corresponding to diameters before and after the establishment of dominance, respectively, during a bovine follicular wave) and exposed to a range of VEGF concentrations (1 to 100 ng/mL) encompassing concentrations found naturally in bovine dominant follicles. A concentration of VEGF of 1 ng/mL induced significant proliferation of granulosa cells from 4- to 8-mm follicles (P=0.024) and increased the proliferative response of these cells to follicle-stimulating hormone (FSH; P=0.045); whereas higher doses of VEGF had no effect on proliferation (P=0.9). Treatment with VEGF induced an overall increase in mean extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation (P=0.02). In contrast, VEGF, alone or in combination with FSH, had no effect on expression of the steroidogenic enzyme, CYP11A1, by cells from 4- to 8-mm follicles (P=0.9). Granulosa cells from 9- to 14-mm follicles responded to 1 ng/mL VEGF with an increase in expression of the ovulation-associated gene, PTGS2 (P=0.003) but higher VEGF doses had no effect (P=0.9). The PTGS2 response to 1 ng/mL VEGF was similar to that induced by treatment with luteinizing hormone (LH). Interestingly, the stimulatory effects of LH on ERK1/2 phosphorylation (P=0.003) and PTGS2 expression (P<0.01) in granulosa cells from 9- to 14-mm follicles were abolished (P=0.2) by specific chemical inhibition of VEGF receptor 2 (VEGFR2). These results suggest novel and important roles of VEGF and its receptor, VEGFR2, in mediating and/or enhancing the effects of gonadotropins in granulosa cells.

Sick notes, general practitioners, emergency departments and fracture clinics.

BACKGROUND: General practitioner waiting times are increasing. The two national surveys regarding general practice showed that the number of patients waiting for >or=2 days for an appointment rose from 63% to 72% between 1998 and 2002, with 25% waiting for >or=4 days. The Department of Health recognised that many patients discharged from hospitals and outpatient clinics required to visit their general practitioner for the sole purpose of obtaining a sick note. The report entitled Making a difference: reducing general practitioner paperwork estimated that 518 000 appointments (and 42 000 GP h) could be saved by ensuring that these patients were issued with a sick note directly from hospital rather than being referred to their general practitioner. This practice was to be adopted from July 2001 and included patients discharged from wards as well as those seen in outpatient departments. METHOD: 50 emergency departments and fracture clinics in Scotland and England were contacted to assess whether these guidelines had been adopted. Only hospitals with both accident and emergency and fracture clinics were included; nurse-led and paediatric departments were excluded. RESULTS: Of the 25 Scottish emergency hospitals contacted, 4 (16%) accident and emergency departments and 8 (32%) fracture clinics issued sick notes. This was compared with 5 of 25 (20%) accident and emergency departments and 12 of 25 (48%) fracture clinics in England. Four Scottish and five English accident and emergency departments stated that it was policy to give sick notes, three Scottish and four English departments said that it was policy not to give them and the rest (72% in Scotland and 64% in England) stated that they had no clear policy but "just don't give them". CONCLUSION: The 2001 guidance from the joint Cabinet Office/Department of Health has not been fully incorporated into standard practice in Scotland and England. If all emergency departments and fracture clinics were to issue sick notes to patients requiring >7 days absence from work, this could reduce general practitioner consultations and improve waiting times.

Walking at work: a pedometer study assessing the activity levels of doctors.

BACKGROUND: The World Health Organisation cites a sedentary lifestyle as one of the top ten causes of morbidity and mortality worldwide.4 A recent, large-scale clinical study showed that brisk walking and vigorous exercise are associated with substantial (and similar) reductions in the incidence of coronary heart disease. Current guidelines suggest 10,000 steps per day as an appropriate activity target for healthy adults. AIMS: This study aims to assess whether doctors are meeting this daily walking target during working-hours, and whether additional out-of-hours exercise is required. METHODS: 16 doctors from St. John's Hospital in Livingston (comprising 4 Medical Consultants, 4 Surgical Consultants, 4 Medical PRHOs and 4 Surgical PRHOs) each used a belt-worn pedometer to record all steps made during 5 consecutive day shifts. Stride length and total daily steps were recorded. Steps made out-with working hours were not counted. Total steps and hours worked were recorded at the end of each day. RESULTS: Average daily steps recorded were 7907 (Medical PRHOs), 5068 (Surgical PRHOs), 4822 (Surgical Consultants) and 4647 (Medical Consultants). P values of < 0.1 were obtained for the variation in steps between the Medical PRHOs and both the Consultant Surgeons and Consultant Physicians. Distance walked per shift varied from 3.84 (Consultant Physicians) to 6.85 kilometres (Medical PRHOs). CONCLUSION: Walking at work does provide a substantial proportion of a doctor's recommended daily activity quota. However, it is still necessary to engage in additional, out-of-hours exercise in order to consistently meet the current recommendations for physical exercise.

Endothelin-1 during and after cardiopulmonary bypass: association to graft sensitivity and postoperative recovery.

OBJECTIVE: Our objectives are 2-fold: (1) to serially measure the release of endothelin and graft-conduit endothelin sensitivity during and after coronary artery bypass grafting and (2) to define potential relationships of changes in endothelin levels to perioperative parameters. METHODS: Endothelin plasma content was measured in patients (n = 105) undergoing bypass grafting from select vascular compartments before operations and at specific intervals up to 24 hours postoperatively. Endothelin sensitivity was determined in isolated internal thoracic artery segments. RESULTS: Systemic arterial and pulmonary arterial endothelin levels were increased by approximately 50% immediately after bypass grafting and increased by another 85% during the first 24 hours postoperatively. Endothelin levels were highest in patients with prolonged ventilatory requirements and extended stays in the intensive care unit (10.2 +/- 0.8 vs 13.2 +/- 1.1 fmol/mL, P =.02, and 9.8 +/- 0.7 vs 13.9 +/- 1.2 fmol/mL, P =.01, respectively. Endothelin sensitivity of the internal thoracic artery was increased in patients requiring prolonged vasodilator support with nitroglycerin. CONCLUSIONS: Systemic and pulmonary arterial endothelin levels remained increased for at least 24 hours postoperatively. Prolonged pharmacologic management and increased intensive care unit stay were associated with increased systemic endothelin release and heightened graft-conduit sensitivity to endothelin.

Endothelin receptor subtype A blockade selectively reduces pulmonary pressure after cardiopulmonary bypass.

BACKGROUND: The bioactive peptide endothelin-1 is elevated during and after cardiopulmonary bypass and exerts cardiovascular effects through its 2 receptor subtypes, endothelin-1A and endothelin-1B. Increased endothelin-1A receptor stimulation after cardiopulmonary bypass can cause increased pulmonary vascular resistance and modulate myocardial contractility. However, whether and to what degree selective endothelin-1A blockade influences these parameters in the postbypass setting is not completely understood. OBJECTIVES: Our objective was to measure left ventricular function and hemodynamics in a porcine model of cardiopulmonary bypass after selective blockade of endothelin-1A. METHODS: Adult pigs (n = 23) underwent 90 minutes of cardiopulmonary bypass and were randomized 30 minutes after bypass to receive a selective endothelin-1A antagonist (TBC 11251, 10 mg/kg; n = 13) or saline vehicle (n = 10). RESULTS: After bypass and before randomization, pulmonary vascular resistance rose nearly 4-fold, and left ventricular preload recruitable stroke work fell to one third of baseline values (both P <.05). In the vehicle group pulmonary vascular resistance continued to rise, and preload recruitable stroke work remained reduced. However, after endothelin-1A blockade, the rise in pulmonary vascular resistance was significantly blunted compared with that in the vehicle group. Moreover, the reduction in pulmonary vascular resistance with endothelin-1A blockade was achieved without a significant change in systemic perfusion pressures. CONCLUSIONS: The present study demonstrated that increased activity of the endothelin-1A receptor likely contributes to alterations in pulmonary vascular resistance in the postbypass setting. Selective endothelin-1A blockade may provide a means to selectively decrease pulmonary vascular resistance without significant effects on systemic hemodynamics.

beta-Adrenergic and endothelin receptor interaction in dilated human cardiomyopathic myocardium.

BACKGROUND: Although end-stage dilated cardiomyopathy (DCM) is characterized by defects in beta-adrenergic receptor (beta-AR) activity and increased endothelin-1 (ET-1), possible interactions between these 2 systems remain to be defined. Accordingly, the goal of this study was to determine the effects of ET receptor activation on beta-AR signaling through measurement of cyclic adenosine monophosphate (cAMP) in normal and DCM myocardium. METHODS AND RESULTS: Myocardial sarcolemmal preparations were prepared from normal human (n = 6), dilated cardiomyopathic (n = 10), and ischemic cardiomyopathic (ICM, n = 10) tissue. Basal cAMP production was measured in the presence of ET-1 alone (10(-6) to 0(-9) mol/L) as well as after (-)isoproterenol (10(-6) to 10(-2) mol/L) or forskolin (0.05 to 30.0 micromol/L) stimulation. beta-AR and ET receptor profiles were determined by radiolabeled ligand assays. ET-1 inhibited basal cAMP production in all preparations in a concentration-dependent manner. However, beta-AR-stimulated cAMP production by either isoproterenol or forskolin was not significantly affected by ET-1. beta-AR receptor density was reduced, and a selective reduction of the ET(B) receptor occurred in both forms of DCM. CONCLUSIONS: Under basal conditions, ET receptor stimulation reduced cAMP levels, which may influence contractility, particularly with DCM.

Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass.

OBJECTIVE: Increased systemic levels of the bioactive peptide endothelin 1 during and after cardioplegic arrest and cardiopulmonary bypass have been well documented. However, endothelin 1 is synthesized locally, and therefore myocardial endothelin 1 production during and after cardiopulmonary bypass remains unknown. METHODS: Pigs (n = 11) were instrumented for cardiopulmonary bypass, and cardioplegic arrest was initiated. Myocardial interstitial and systemic arterial levels of endothelin 1 were measured before cardiopulmonary bypass, throughout bypass and cardioplegic arrest (90 minutes), and up to 90 minutes after separation from bypass. Myocardial interstitial endothelin 1 was determined by microdialysis and radioimmunoassay. RESULTS: Baseline myocardial endothelin 1 levels were higher than systemic endothelin 1 levels (25.6 +/- 6.7 vs 8.3 +/- 1.1 fmol/mL, P <.05). With the onset of bypass, myocardial endothelin 1 increased by 327% +/- 92% from baseline (P <.05), which preceded the increase in systemic endothelin 1 levels. CONCLUSION: Myocardial compartmentalization of endothelin 1 exists in vivo. Cardiopulmonary bypass and cardioplegic arrest induce temporal differences in endothelin 1 levels within the myocardial interstitium and systemic circulation, which, in turn, may influence left ventricular function in the postbypass period.

Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery.

OBJECTIVE: To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN: Prospective, clinical study. SETTING: University hospital. PARTICIPANTS: Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS: Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION: Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.

ET-1 in the myocardial interstitium: relation to myocyte ECE activity and expression.

Increased plasma levels of endothelin-1 (ET-1) have been identified in congestive heart failure (CHF), but local myocardial interstitial ET-1 levels and the relation to determinants of ET-1 synthesis remain to be defined. Accordingly, myocardial interstitial ET-1 levels and myocyte endothelin-converting enzyme (ECE)-1 activity and expression with the development of CHF were examined. Pigs were instrumented with a microdialysis system to measure myocardial interstitial ET-1 levels with pacing CHF (240 beats/min, 3 wk; n = 9) and in controls (n = 14). Plasma ET-1 was increased with CHF (15 +/- 1 vs. 9 +/- 1 fmol/ml, P < 0.05) as was total myocardial ET-1 content (90 +/- 15 vs. 35 +/- 5 fmol/g, P < 0.05). Paradoxically, myocardial interstitial ET-1 was decreased in CHF (32 +/- 4 vs. 21 +/- 2 fmol/ml, P < 0.05), which indicated increased ET-1 uptake by the left ventricular (LV) myocardium with CHF. In isolated LV myocyte preparations, ECE-1 activity was increased by twofold with CHF (P < 0.05). In LV myocytes, both ECE-1a and ECE-1c mRNAs were detected, and ECE-1a expression was upregulated fivefold in CHF myocytes (P < 0.05). In conclusion, this study demonstrated compartmentalization of ET-1 in the myocardial interstitium and enhanced ET-1 uptake with CHF. Thus a local ET-1 system exists at the level of the myocyte, and determinants of ET-1 biosynthesis are selectively regulated within this myocardial compartment in CHF.

Mapping of quantitative trait loci on porcine chromosome 4.

A F2 population derived from a cross between European Large White and Chinese Meishan pigs was established in order to study the genetic basis of breed differences for growth and fat traits. Chromosome 4 was chosen for initial study as previous work had revealed quantitative trait loci (QTLs) on this chromosome affected growth and fat traits in a Wild Boar x Large White cross. Individuals in the F2 population were typed for nine markers spanning a region of approximately 124 CM. We found evidence for QTLs affecting growth between weaning and the end of test (additive effect: 43.4 g/day) and fat depth measured in the mid-back position (additive effect: 1.82 mm). There was no evidence of interactions between the QTLs and sex, grandparents or F1 sires, suggesting that the detected QTLs were fixed for alternative alleles in the Meishan and Large White breeds. Comparison of locations suggests that these QTLs could be the same as those found in the Wild Boar x Large White cross.

Coalescing the theories of two nurse visionaries: Parse and Watson.

The theories of two nurse visionaries, Rosemarie Rizzo Parse and Jean Watson, are examined for areas of agreement and notable differences. Watson and Parse reject (or hold seriously suspect) traditional, positivistic methods of studying human behaviour and posit their theories as alternatives to the totality paradigm. Since both of these theories, Parse's theory of human becoming and Watson's theory of transpersonal care, borrow heavily from existential phenomenology, major tenets of this philosophic perspective are outlined. Each theory is then described with emphasis on anchoring motifs, concepts, and principles. Next both theories are analysed and critiqued simultaneously. Finally, the theories are applied to a case study with the intent of maximizing their mutual strengths and diminishing their limitations. Coalescence of compatible theories is recommended as a way of enhancing the application of nursing knowledge in practice.

No association between p53 status and alpha-particle-induced chromosomal instability in human lymphoblastoid cells.

Previous work has demonstrated that alpha-particle irradiation of primary human bone marrow cells leads to the transmission of chromosomal instability in the descendants of the irradiated cell, although there is some interindividual variation. We have extended these studies to human EBV-transformed lymphoblastoid cell lines in order to establish an in vitro model system. The five cell lines analyzed, including one from a Fanconi anaemia patient, exhibited high levels of persistent chromatid aberrations up to approximately 40 cell generations after alpha-irradiation. The p53 status of the cell lines was defined according to whether cellular p53 levels were induced by irradiation, translocated to the nucleus and were able to bind a p53 DNA consensus recognition sequence in vitro. Together with the primary bone marrow cell studies, we conclude that alpha-particle induced chromosomal instability is independent of the p53 status of the cell as defined in these studies.

FIRO-B: the power of love and the love of power.

Factor analysis of FIRO-B data obtained from new software product teams had led to a reformulation of Schutz's ideas on team compatibility. The concept of Group-Warmth as a derivative of the FIRO-B Inclusion and Affection scales was developed and shown to be related to the commercial effectiveness of teams. In a like manner, the FIRO-B constructs of Control-Expressed and Control-Wanted were explored through concurrent factor analysis of 16 PF data. A new interpretation has been given to both FIRO-B Control scales, namely, Assertive-Impulsive.