Superconducting-qubit readout via low-backaction electro-optic transduction.

Entangling microwave-frequency superconducting quantum processors through optical light at ambient temperature would enable means of secure communication and distributed quantum information processing1. However, transducing quantum signals between these disparate regimes of the electro-magnetic spectrum remains an outstanding goal2-9, and interfacing superconducting qubits, which are constrained to operate at millikelvin temperatures, with electro-optic transducers presents considerable challenges owing to the deleterious effects of optical photons on superconductors9,10. Moreover, many remote entanglement protocols11-14 require multiple qubit gates both preceding and following the upconversion of the quantum state, and thus an ideal transducer should impart minimal backaction15 on the qubit. Here we demonstrate readout of a superconducting transmon qubit through a low-backaction electro-optomechanical transducer. The modular nature of the transducer and circuit quantum electrodynamics system used in this work enable complete isolation of the qubit from optical photons, and the backaction on the qubit from the transducer is less than that imparted by thermal radiation from the environment. Moderate improvements in the transducer bandwidth and the added noise will enable us to leverage the full suite of tools available in circuit quantum electrodynamics to demonstrate transduction of non-classical signals from a superconducting qubit to the optical domain.

Treatment of acute aneurysmal subarachnoid haemorrhage with primary flow diversion: 5-year single-centre experience.

AIM: To evaluate the safety and efficacy of treatment of patients presenting with acute aneurysmal subarachnoid haemorrhage (SAH) with primary flow-diverting stents (FDS; with or without adjuncts), with comparison to the published literature. MATERIALS AND METHODS: A retrospective single-centre review was undertaken of prospectively obtained data on patients treated for SAH over a 60-month period. Of 354 patients treated for SAH during that time period, 24 patients with a total of 25 aneurysms were identified. Baseline patient demographics were recorded and clinical and imaging outcomes assessed. RESULTS: Eighty-eight per cent (22/25) of the aneurysms were completely occluded (Raymond-Roy 1) at mean 12-month follow-up. The minor complication rate was 12.5% (3/24) without permanent morbidity. Mortality rate was 4% (1/25) after one patient died following aneurysmal rebleed on day 7 post-procedure. Forty-two per cent (10/24) of patients had a high-pressure shunt placed prior to endovascular treatment, no haemorrhagic complications of neurosurgical intervention were observed. CONCLUSION: The necessity of dual antiplatelet therapy (DAPT) therapy when deploying FDS will rightly continue to limit their use in the acutely ruptured setting to a case-by-case basis whereby other treatment options are deemed unsafe. Methods employed to minimise subsequent haemorrhagic risks from DAPT in these patients may be worthy of further investigation.

Postbiotics produced at laboratory and industrial level as potential functional food ingredients with the capacity to protect mice against Salmonella infection.

AIM: To determine the protective capacity against Salmonella infection in mice of the cell-free fraction (postbiotic) of fermented milk, produced at laboratory and industrial level. METHODS AND RESULTS: The proteolytic activity (PA) of 5 commercial cultures and 11 autochthonous Lactobacillus strains was evaluated. The DSM-100H culture displayed the highest PA and it was selected for further studies. The capacity of the postbiotics produced by pH-controlled fermentation to stimulate the production of secretory IgA in faeces and to protect mice against Salmonella infection was evaluated. A significant increase in secretory IgA in faeces of mice fed 14 days the postbiotic obtained at the laboratory (F36) was detected compared to control animals. A significantly higher survival was observed in mice fed the F36 and the FiSD (industrial product) compared to controls. CONCLUSION: The postbiotics obtained showed immunomodulatory and protective capacity against Salmonella infection in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: The pH-controlled milk fermentation by the proteolytic DSM-100H culture could be a suitable strategy to obtain a food ingredient to be added to a given food matrix, not adequate to host viable cells of probiotics, to confer it enhanced functionality and thus expand the functional food market.

Novel bifidobacteria strains isolated from nonconventional sources. Technological, antimicrobial and biological characterization for their use as probiotics.

AIM: To characterize four novel autochthonous bifidobacteria isolated from monkey faeces and a Bifidobacterium lactis strain isolated from chicken faeces by evaluating their technological and biological/functional potential to be used as probiotics. Different stressors, including food process parameters and storage, can affect their viability and functionality. METHODS AND RESULTS: The resistance to frozen storage, tolerance to lyophilization and viability during storage, thermal, acidic and simulated gastric resistance, surface hydrophobicity and antimicrobial activity against pathogens were studied. Bifidobacterium lactis Bb12 and INL1 were used as reference strains. The results obtained demonstrated that the new isolates presented strain-dependent behaviour. Good results were obtained for thermal resistance, frozen storage at -80°C and lyophilized powders maintained at 5°C. Cell viability during refrigerated storage was higher when the strains were resuspended in milk at pH 5·0 than at 4·5. The surface hydrophobicity ranged between 7 and 98% depending on the strain. The simulated gastric resistance was improved for the strains incorporated in cheese. Regarding antimicrobial activity, bifidobacteria isolated from monkey presented higher inhibitory capacity than the reference strains. CONCLUSION: This research provides a deeper insight into new strains of bifidobacteria isolated from primates and chicken that have not been previously characterized for their potential use in dairy products and confirm the most robust stress tolerance of B. lactis. SIGNIFICANCE AND IMPACT OF THE STUDY: The possibility of expanding the available bifidobacteria with the potential to be added to a probiotic food necessarily implies characterizing them from different points of view, especially when considering unknown species. For monkey isolates (which showed higher antimicrobial activity against pathogens), more in-depth knowledge is needed before applying strategies to improve their performance. On the contrary, the chicken isolate B. lactis P32/1 showed similar behaviour to the references B. lactis strains; therefore, it could be considered as a potential probiotic candidate.

Study of the effects of spray drying in whey-starch on the probiotic capacity of Lactobacillus rhamnosus 64 in the gut of mice.

AIMS: To evaluate the effects of spray drying of Lactobacillus rhamnosus 64 on its capacity to modulate the gut immune response and on the attenuation of TNBS-induced colitis in mice. METHODS AND RESULTS: Lactobacillus rhamnosus 64 was spray dried in cheese whey-starch solution and administered to mice for 3, 6 or 10 consecutive days. Peritoneal macrophage phagocytic activity, secretory IgA levels in the small intestinal fluid and TNFα, IFNγ, IL-10, IL-6 and IL-2 levels in homogenates of the small and large intestine were determined. The effects of spray drying were also evaluated in an acute model of Trinitrobenzenesulfonic acid (TNBS)-induced colitis. A shift in the regulation of immune parameters, particularly the cytokine profile, was observed for mice treated with the spray-dried culture, compared to the profile observed in animals that received the strain as fresh culture (FC). The spray-dried culture of L. rhamnosus 64 showed anti-inflammatory properties in murine model of TNBS-induced colitis. CONCLUSIONS: The spray-drying process of L. rhamnosus 64 in whey-starch modified its immunomodulating capacity in healthy animals and conferred enhanced protection in an in vivo model of inflammation. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotic capacity can be affected by spray drying in relation to the properties observed for the strain as an overnight FC. This fact should be taken into account when producing the culture for its application in the industry.

Effects of circuit resistance training and timely protein supplementation on exercise-induced fat oxidation in tetraplegic adults.

BACKGROUND: Substrate utilization during exercise in persons with spinal cord injury (SCI) remains poorly defined. PURPOSE: To investigate effects of circuit resistance training (CRT) and timing of protein supplementation (PS) on fuel utilization in persons with tetraplegia. METHODS: Eleven individuals with chronic tetraplegia underwent 6 months of CRT 3 times weekly. Five randomly assigned participants received immediate PS (iPS) administered in split doses prior to and following all exercise sessions. Other participants consumed a matched dose of PS that was delayed until 24 hours post-exercise (dPS). Participants underwent a maximal graded exercise test (GXT) to volitional exhaustion at 4 conditioning time points: 3 months before (-3mo), at the beginning of (0mo), 3 months into (3mo), and 6 months following (6mo) the CRT conditioning program. Respiratory measures were continuously obtained throughout the GXT via open-circuit spirometry. Fuel utilization and energy expenditure were computed from the respiratory data. RESULTS: The differences in changes in substrate utilization between the PS groups were not significant as determined by the interaction of PS group and conditioning time point, F (3, 27) = 2.32, P = .098, η(2) P = .205. Maximal absolute fat oxidation did not change significantly from 0 to 6mo (mean difference, 0.014 ± 0.031 g/min; P = .170), and fat oxidation remained low never exceeding an average of 0.10 ± 0.09 g/min for any given exercise intensity. CONCLUSION: Maximum fat utilization during exercise and fat utilization at matched exercise intensities were not increased in persons with tetraplegia, independent of PS, and levels of fat oxidation remained low after training.

Evaluation of the NucliSENS EasyQ KPC assay for detection of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae.

The NucliSENS EasyQ KPC assay (bioMérieux SA, Marcy l'Etoile, France) was compared with a routinely used phenotypic method for detection of Enterobacteriaceae producing Klebsiella pneumoniae carbapenemase (KPC)-type carbapenemases, using 806 stool samples and rectal swabs. Compared with the phenotypic method, the EasyQ KPC assay had a sensitivity and specificity of 93.3% and 99.0%, respectively, in this setting, with diverse KPC producers not limited to ST258 Klebsiella pneumoniae.

Long-term renal outcomes of consecutive patients undergoing open type IV thoracoabdominal aneurysm repair.

OBJECTIVE: To evaluate long-term renal outcomes after open type IV thoracoabdominal aneurysm (TAAA) repair. DESIGN: Retrospective analysis of a prospectively collected database of consecutive operated non-ruptured type IV TAAAs (2007-2011). METHODS: Renal function was analysed by serum creatinine concentration, estimated glomerular filtration rate (eGFR) and Kidney Disease Outcomes Quality Initiative (KDOQI) stage. The primary outcome was the change in creatinine concentration from before surgery to defined time points after surgery: peak postoperative; discharge; at follow-up (>1 year postoperatively). Secondary outcomes were change in eGFR, change in KDOQI stage, dialysis requirement, and 30-day mortality. RESULTS: Between 2007 and 2011, 53 open type IV TAAA repairs were performed. Median creatinine levels significantly increased in the immediate postoperative period, but returned to baseline by discharge. Thirteen patients (28.2%) had an improvement in follow-up eGFR of at least 20% compared with pre-operative eGFR or improved by one KDOQI stage. Twelve patients (26.1%) had a decline in eGFR of at least 20% or one KDOQI stage at follow-up. Three patients (7.5%) required temporary dialysis and one patient (1.9%) required permanent dialysis. The 30-day mortality was 1.9%. CONCLUSIONS: This study demonstrates acceptable renal outcomes following open type IV TAAA repair. Open type IV repair remains the standard against which newer techniques should be compared.

Aortic valve replacement with and without coronary artery bypass graft surgery in octogenarians: is it safe and feasible?

INTRODUCTION: Octogenarians are often denied complex surgical intervention. We evaluated the rationality of this bias by comparing the outcomes of octogenarians undergoing aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG), to those of younger patients. METHODS: Data on 476 patients (≥ 80 years) who underwent AVR or AVR/CABG were compared to the Society of Thoracic Surgeons (STS) database. RESULTS: One hundred and seventeen octogenarians underwent AVR and 263 underwent AVR/CABG. Preoperative comorbidity rates were similar between these 2 respective groups, except for diabetes mellitus (18.8 vs. 30.4%, p = 0.02), previous cardiac stent placement (5.1 vs. 17.9%, p = 0.0006) and prior CABG (8.5 vs. 0.8%, p = 0.0002) and mortality did not differ significantly (5.1 vs. 7.6%, p = 0.51). Multivariate analysis identified preoperative chronic renal failure [odds ratio (OR) = 0.09, p < 0.048], postoperative arrhythmia (OR = 0.29, p < 0.022), sepsis (OR =37.38, p < 0.000), pneumonia (OR = 8.29, p < 0.038) and renal failure (OR = 10.16, p < 0.000) with increased rates of in hospital mortality in AVR alone and AVR/CABG. CONCLUSION: AVR alone or AVR/CABG can be safely performed in patients ≥ 80 years with acceptable morbidity/mortality rates. An age of ≥ 80 years is not an independent risk factor predictive of increased in hospital mortality

Mechanisms of microbubble-vessel interactions and induced stresses: a numerical study.

Oscillating microbubbles within microvessels could induce stresses that lead to bioeffects or vascular damage. Previous work has attributed vascular damage to the vessel expansion or bubble jet. However, ultra-high speed images of recent studies suggest that it could happen due to the vascular invagination. Numerical simulations of confined bubbles could provide insight into understanding the mechanism behind bubble-vessel interactions. In this study, a finite element model of a coupled bubble/fluid/vessel system was developed and validated with experimental data. Also, for a more realistic study viscoelastic properties of microvessels were assessed and incorporated into this comprehensive numerical model. The wall shear stress (WSS) and circumferential stress (CS), metrics of vascular damage, were calculated from these simulations. Resultant amplitudes of oscillation were within 15% of those measured in experiments (four cases). Among the experimental cases, it was numerically found that maximum WSS values were between 1.1-18.3 kPa during bubble expansion and 1.5-74 kPa during bubble collapse. CS was between 0.43-2.2 MPa during expansion and 0.44-6 MPa while invaginated. This finding confirmed that vascular damage could occur during vascular invaginations. Predicted thresholds in which these stresses are higher during vessel invagination were calculated from simulations.

Experiences of the SARS-CoV-2 pandemic amongst Australian healthcare workers: from stressors to protective factors.

BACKGROUND: The SARS-CoV-2 pandemic has critically challenged healthcare systems globally. Examining the experiences of healthcare workers (HCWs) is important for optimizing ongoing and future pandemic responses. OBJECTIVES: In-depth exploration of Australian HCWs' experiences of the SARS-CoV-2 pandemic, with a focus on reported stressors vis-à-vis protective factors. METHODS: Individual interviews were performed with 63 HCWs in Australia. A range of professional streams and operational staff were included. Thematic analysis was performed. RESULTS: Thematic analysis identified stressors centred on paucity of, or changing, evidence, leading to absence of, or mistrust in, guidelines; unprecedented alterations to the autonomy and sense of control of clinicians; and deficiencies in communication and support. Key protective factors included: the development of clear guidance from respected clinical leaders or recognized clinical bodies, interpersonal support, and strong teamwork, leadership, and a sense of organizational preparedness. CONCLUSIONS: This study provides insights into the key organizational sources of emotional stress for HCWs within pandemic responses and describes experiences of protective factors. HCWs experiencing unprecedented uncertainty, fear, and rapid change, rely on clear communication, strong leadership, guidelines endorsed by recognized expert groups or individuals, and have increased reliance on interpersonal support. Structured strategies for leadership and communication at team, service group and organizational levels, provision of psychological support, and consideration of the potential negative effects of centralizing control, would assist in ameliorating the extreme pressures of working within a pandemic environment.

ASPM and microcephalin expression in epithelial ovarian cancer correlates with tumour grade and survival.

BACKGROUND: The clinico-pathological and molecular heterogeneity of epithelial ovarian cancer (EOC) complicates its early diagnosis and successful treatment. Highly aneuploid tumours and the presence of ascitic fluids are hallmarks of EOC. Two microcephaly-associated proteins, abnormal spindle-like microcephaly-associated protein (ASPM) and microcephalin, are involved in mitosis and DNA damage repair. Their expression is deregulated at the RNA level in EOC. Here, ASPM and microcephalin protein expression in primary cultures established from the ascites of patients with EOC was determined and correlated with clinical data to assess their suitability as biomarkers. METHODS: Five established ovarian cancer cell lines, cells derived from two benign ovarian ascites samples and 40 primary cultures of EOC derived from ovarian ascites samples were analysed by protein slot blotting and/or immunofluorescence to determine ASPM and microcephalin protein levels and their cellular localisation. Results were correlated with clinico-pathological data. RESULTS: A statistically significant correlation was identified for ASPM localisation and tumour grade, with high levels of cytoplasmic ASPM correlating with grade 1 tumours. Conversely, cytoplasmic microcephalin was only identified in high-grade tumours. Furthermore, low levels of nuclear microcephalin correlated with reduced patient survival. CONCLUSION: Our results suggest that ASPM and microcephalin have the potential to be biomarkers in ovarian cancer.

Asthma and ageing: an end user's perspective--the perception and problems with the management of asthma in the elderly.

Despite the high prevalence of asthma in the elderly, its development, diagnosis, and treatment are under-researched. This paper provides a comprehensive review of the current state of knowledge in relation to management of asthma in the elderly - focusing on barriers to diagnosis and treatment and the central role of self-management. Asthma prevalence increases with age, as does the risk of dying from asthma, and with the ageing of the population and increasing life expectancy, the prevalence of (diagnosed and undiagnosed) asthma in older adults is expected to increase drastically, placing an increasing burden on sufferers, the community and health budgets. Asthma sufferers are more likely to be psychologically distressed and at a higher risk of anxiety and depression, more likely to experience a sense of lack of control over their health and to have lower self-reported quality of life. Asthma is under-diagnosed, and under-treated, in the elderly, further exacerbating these negative consequences. The review concludes, among other things, that there is a need to better understand the development and impact of asthma in the elderly, to increase community awareness of asthma in the elderly, to improve both 'medical management' and 'self-management' in this population and to develop more effective tools for diagnosis and treatment of asthma in the elderly. The paper concludes with key recommendations for future research and practice in this area.

Happy Hookers: findings from an international study exploring the effects of crochet on wellbeing.

AIMS: With rising rates of mental health disorders being reported globally, it is imperative that we investigate economical and accessible ways to increase relaxation and reduce stress. While there is a plethora of anecdotal evidence as to the positive effects of domestic crafts on mental wellbeing, there is little empirical research in this area. As such, we aimed to explore perceived links between crochet and wellbeing. METHODS: An online survey was developed and piloted, based on an existing tool that explored knitting and wellbeing. The final survey was promoted through social media, over a 6-week period, resulting in valid responses from 8391 individuals. RESULTS: Most respondents were female (99.1%), aged between 41 and 60 years (49.5%) and living in 87 different countries. Many respondents reported crocheting for between 1 and 5 years (42.6%). The three most frequent reasons reported for crocheting were: to be creative (82.1%), to relax (78.5%) and for a sense of accomplishment (75.2%). Respondents reported that crochet made them feel calmer (89.5%), happier (82%) and more useful (74.7%). There was a significant improvement in reported scores for mood before crocheting (M = 4.19, SD = 1.07) and mood after crocheting (M = 5.78, SD = 0.82); z = -69.86, p < .001, r = -0.56. Content analysis of free-text responses identified five major themes: (1) health benefits, (2) process of crochet, (3) personal connection, (4) crochet as contribution and (5) online crochet communities. CONCLUSION: The data suggests that crochet offers positive benefits for personal wellbeing with many respondents actively using crochet to manage mental health conditions and life events such as grief, chronic illness and pain. Crochet is a relatively low-cost, portable activity that can be easily learnt and seems to convey all of the positive benefits provided by knitting. This research suggests that crochet can play a role in promoting positive wellbeing in the general population, adding to the social prescribing evidence base.

Disconnect between standardized field-based testing and mannitol challenge in Scottish elite swimmers.

BACKGROUND: Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity. OBJECTIVE: To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field-based exercise challenge. METHODS: The Scottish national squad underwent exhaled tidal (FE(NO)) and nasal (N(NO)) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4-6 h post-swimming. A sport-specific exercise test was carried out during an intensive lactate set (8 min at >/=80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire. RESULTS: N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FE(NO) (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FE(NO) was observed pre vs. immediate and delayed post-chlorine exposure: mean (95% CI) 18.7 (15.9-22.0) p.p.b. vs. 15.9 (13.3-19.1) p.p.b. (P<0.01), and 13.9 (11.5-16.7) p.p.b. (P<0.01), respectively. There were no significant differences in N(NO.) Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post-exposure (P<0.01). Delayed post-exposure PNIF was not significantly different from pre-exposure. CONCLUSIONS: No association was found between mannitol and standardized field-based testing in elite swimmers. Mannitol was associated with a high baseline FE(NO); however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a 'traditional' inflammatory asthmatic phenotype, while field-based exercise/chlorine challenge may identify a swimmer-specific bronchoconstrictor response. A sustained fall in FE(NO) following chlorine exposure suggests that a non-cellular, perhaps neurogenic, response may be involved in this group of athletes.

Suitability of buttermilk for fermentation with Lactobacillus helveticus and production of a functional peptide-enriched powder by spray-drying.

AIM: To ferment buttermilk, a low-cost by-product of the manufacture of butter, with a proteolytic strain of Lactobacillus helveticus, to enhance its value by the production of a functional peptide-enriched powder. METHODS AND RESULTS: Buttermilk was fermented with Lact. helveticus 209, a strain chosen for its high proteolytic activity. To enhance the release of peptidic fractions, during fermentation pH was kept at 6 by using NaOH, Ca(CO)(3) or Ca(OH)(2). Cell-free supernatant was recovered by centrifugation, supplemented or not with maltodextrin and spray-dried. The profile of peptidic fractions released was studied by RP-HPLC. The lactose, Na and Ca content was also determined. The powder obtained was administered to BALB/c mice for 5 or 7 consecutive days, resulting in the proliferation of IgA-producing cells in the small intestine mucosa of the animals. CONCLUSIONS: Buttermilk is a suitable substrate for the fermentation with Lact. helveticus 209 and the release of peptide fractions able to be spray-dried and to modulate the gut mucosa in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: A powder enriched with peptides released from buttermilk proteins, with potential applications as a functional food additive, was obtained by spray-drying. A novel use of buttermilk as substrate for lactic fermentation is reported.

Occurrence of bacteria with technological and probiotic potential in Argentinian human breast-milk.

Breast milk can be a source of potential probiotic bacteria, but the technological capacity of isolates obtained from this source is not always guaranteed. We aimed at isolating lactobacilli from breast milk samples collected in Argentina, focusing on isolates with functional and technological potential as probiotics. Fourteen Lactobacillus and one Bifidobacterium isolates were obtained from 164 samples donated by 104 mothers. The isolates preliminarily identified by MALDI-TOF, and then the identity was confirmed by partial 16S rRNA gene sequencing. Hydrophobicity was determined (hexadecane and xylene partition). The strains were also co-cultured with murine RAW 264.7 macrophages for screening the capacity to induce the anti-inflammatory cytokine interleukin (IL)-10. Hydrophobicity ranged from 7.4 and 95.9%. The strains Lactobacillus gasseri (70a and 70c) and Lactobacillus plantarum (73a and 73b) were the strains with a higher capacity to induce IL-10 production by macrophages. The technological application was evaluated by freezing dried in 10% lactose or 10% polydextrose. The survival was assessed after accelerated (37 °C, 4 weeks) or long-term (5 and 25 °C, 12 months) storage. Except for Lactobacillus gallinarum 94d, strains lost less than 1 Log10 order cfu/g after long-term (12 months) storage at 5 °C in lactose and polydextrose as protectants. A low correlation between survival to accelerated and long-term storage tests was observed. L. gasseri (70a and 70c) and L. plantarum (73a and 73b) deserve further studies as potential probiotics due to their capacity to induce IL-10 from murine macrophages and their hydrophobicity. In special, L. plantarum 73a was able to confer enhanced protection against Salmonella infection by promoting the immunity of the small intestine.

Hypothermic responses to infection are inhibited by alpha2-adrenoceptor agonists with possible clinical implications.

BACKGROUND: alpha(2)-Adrenoceptor agonists are currently used as primary sedative agents in high dependency patients who are at high risk of sepsis. Clinical surveillance of such patients relies in part on their ability to mount appropriate responses to infection, in particular thermal responses. Thermoregulatory responses to infection are well studied in the rat and in this species, and humans, infection can induce febrile, hypothermic, or mixed hypothermic and febrile responses. The involvement of noradrenergic systems in thermal responses to infection prompted the hypothesis that ligands that act on adrenoceptors may interfere with the normal thermal responses to infection. METHODS: In this study on rats, the effect of infusion of the selective alpha(2)-agonist, mivazerol, on hypothermic and plasma corticosterone responses induced by bacterial lipopolysaccharide (LPS) was investigated. RESULTS: Clinically effective doses of mivazerol (4.8 and 10 microg kg(-1) h(-1)) had no effect on body temperature alone. However, mivazerol significantly inhibited the typical thermoregulatory response to bacterial LPS in a dose-dependent manner. This effect was mimicked by the selective alpha(2)-agonist, UK14304-18 (6 microg kg(-1) h(-1)), and antagonized by the alpha(2)-antagonist, RX811059A (7 microg kg(-1) h(-1)). The alpha(2)-ligands had no effect on basal or LPS-induced corticosterone levels. CONCLUSIONS: These data suggest that early thermoregulatory responses to infection can be selectively antagonized by ligands that activate alpha(2)-adrenoreceptors. High dependency patients receiving alpha(2)-adrenoceptor agonists may not be capable of mounting a normal thermal response to infecting organisms and clinical monitoring using core temperature to detect infection may therefore be unreliable in these vulnerable patients.

Spontaneous clearance of hepatitis C after liver and renal transplantation.

Spontaneous clearance of hepatitis C virus (HCV) is rare in immunocompromised patients, such as those who have undergone organ transplantation. It has been recognized that patients receiving liver transplantation for HCV-related disease have decreased graft and patient survival compared with those transplanted for other etiologies. There is a growing trend toward treating HCV recurrence aggressively after liver transplantation. For other organ transplant recipients with concurrent HCV, treatment is not often an option, given the high rates of graft rejection and loss secondary to interferon and its immunomodulatory effects. Although spontaneous clearance of HCV has been reported in recipients of solitary liver and renal transplants, a common factor arising in these cases has been previous exposure to interferon. To date, no reports of spontaneous clearance of HCV RNA have been reported in a multiorgan transplant recipient. A case of spontaneous clearance of HCV RNA in an immunocompromised patient, within five months of simultaneous liver and kidney retransplantation is described. Importantly, this patient had no previous exposure to interferon.