Impact of Ocean Warming and Ocean Acidification on Larval Development and Calcification in the Sea Urchin Tripneustes gratilla

Background

As the oceans simultaneously warm, acidify and increase in P _CO2, prospects for marine biota are of concern. Calcifying species may find it difficult to produce their skeleton because ocean acidification decreases calcium carbonate saturation and accompanying hypercapnia suppresses metabolism. However, this may be buffered by enhanced growth and metabolism due to warming.

Methodology/Principal Findings

We examined the interactive effects of near-future ocean warming and increased acidification/P _CO2 on larval development in the tropical sea urchin Tripneustes gratilla. Larvae were reared in multifactorial experiments in flow-through conditions in all combinations of three temperature and three pH/P _CO2 treatments. Experiments were placed in the setting of projected near future conditions for SE Australia, a global change hot spot. Increased acidity/P _CO2 and decreased carbonate mineral saturation significantly reduced larval growth resulting in decreased skeletal length. Increased temperature (+3°C) stimulated growth, producing significantly bigger larvae across all pH/P _CO2 treatments up to a thermal threshold (+6°C). Increased acidity (-0.3-0.5 pH units) and hypercapnia significantly reduced larval calcification. A +3°C warming diminished the negative effects of acidification and hypercapnia on larval growth.

Conclusions and Significance

This study of the effects of ocean warming and CO₂ driven acidification on development and calcification of marine invertebrate larvae reared in experimental conditions from the outset of development (fertilization) shows the positive and negative effects of these stressors. In simultaneous exposure to stressors the dwarfing effects of acidification were dominant. Reduction in size of sea urchin larvae in a high P _CO2 ocean would likely impair their performance with negative consequent effects for benthic adult populations.     

Individual Variability in Reproductive Success Determines Winners and Losers under Ocean Acidification: A Case Study with Sea Urchins

Background

Climate change will lead to intense selection on many organisms, particularly during susceptible early life stages. To date, most studies on the likely biotic effects of climate change have focused on the mean responses of pooled groups of animals. Consequently, the extent to which inter-individual variation mediates different selection responses has not been tested. Investigating this variation is important, since some individuals may be preadapted to future climate scenarios.

Methodology/Principal Findings

We examined the effect of CO₂-induced pH changes (“ocean acidification”) in sperm swimming behaviour on the fertilization success of the Australasian sea urchin Heliocidaris erythrogramma, focusing on the responses of separate individuals and pairs. Acidification significantly decreased the proportion of motile sperm but had no effect on sperm swimming speed. Subsequent fertilization experiments showed strong inter-individual variation in responses to ocean acidification, ranging from a 44% decrease to a 14% increase in fertilization success. This was partly explained by the significant relationship between decreases in percent sperm motility and fertilization success at ΔpH = 0.3, but not at ΔpH = 0.5.

Conclusions and Significance

The effects of ocean acidification on reproductive success varied markedly between individuals. Our results suggest that some individuals will exhibit enhanced fertilization success in acidified oceans, supporting the concept of ‘winners’ and ‘losers’ of climate change at an individual level. If these differences are heritable it is likely that ocean acidification will lead to selection against susceptible phenotypes as well as to rapid fixation of alleles that allow reproduction under more acidic conditions. This selection may ameliorate the biotic effects of climate change if taxa have sufficient extant genetic variation upon which selection can act.     

Aluminium tolerance and high phosphorus efficiency helps Stylosanthes better adapt to low-P acid soils

Backgrond and Aims

Stylosanthes spp. (stylo) is one of the most important pasture legumes used in a wide range of agricultural systems on acid soils, where aluminium (Al) toxicity and phosphorus (P) deficiency are two major limiting factors for plant growth. However, physiological mechanisms of stylo adaptation to acid soils are not understood.

Methods

Twelve stylo genotypes were surveyed under field conditions, followed by sand and nutrient solution culture experiments to investigate possible physiological mechanisms of stylo adaptation to low-P acid soils.

Key Results

Stylo genotypes varied substantially in growth and P uptake in low P conditions in the field. Three genotypes contrasting in P efficiency were selected for experiments in nutrient solution and sand culture to examine their Al tolerance and ability to utilize different P sources, including Ca-P, K-P, Al-P, Fe-P and phytate-P. Among the three tested genotypes, the P-efficient genotype ‘TPRC2001-1’ had higher Al tolerance than the P-inefficient genotype ‘Fine-stem’ as indicated by relative tap root length and haematoxylin staining. The three genotypes differed in their ability to utilize different P sources. The P-efficient genotype, ‘TPRC2001-1’, had superior ability to utilize phytate-P.

Conclusions

The findings suggest that possible physiological mechanisms of stylo adaptation to low-P acid soils might involve superior ability of plant roots to tolerate Al toxicity and to utilize organic P and Al-P.Key words: Stylosanthes, phosphorus, P efficiency, organic P, Al toxicity, acid soil     

Effect on adherence to nicotine replacement therapy of informing smokers their dose is determined by their genotype: a randomised controlled trial

Background

The behavioural impact of pharmacogenomics is untested. We tested two hypotheses concerning the behavioural impact of informing smokers their oral dose of NRT is tailored to analysis of DNA.

Methods and Findings

We conducted an RCT with smokers in smoking cessation clinics (N = 633). In combination with NRT patch, participants were informed that their doses of oral NRT were based either on their mu-opioid receptor (OPRM1) genotype, or their nicotine dependence questionnaire score (phenotype). The proportion of prescribed NRT consumed in the first 28 days following quitting was not significantly different between groups: (68.5% of prescribed NRT consumed in genotype vs 63.6%, phenotype group, difference  =  5.0%, 95% CI −0.9,10.8, p  =  0.098). Motivation to make another quit attempt among those (n  =  331) not abstinent at six months was not significantly different between groups (p  =  0.23). Abstinence at 28 days was not different between groups (p = 0.67); at six months was greater in genotype than phenotype group (13.7% vs 7.9%, difference  =  5.8%, 95% CI 1.0,10.7, p  =  0.018).

Conclusions

Informing smokers their oral dose of NRT was tailored to genotype not phenotype had a small, statistically non-significant effect on 28-day adherence to NRT. Among those still smoking at six months, there was no evidence that saying NRT was tailored to genotype adversely affected motivation to make another quit attempt. Higher abstinence rate at six months in the genotype arm requires investigation.

Trial registration

Controlled-Trials.com ISRCTN14352545.     

Combined effects of two ocean change stressors, warming and acidification, on fertilization and early development of the Antarctic echinoid Sterechinus neumayeri

The effects of concurrent ocean warming and acidification on Antarctic marine benthos warrant investigation as little is known about potential synergies between these climate change stressors. We examined the interactive effects of warming and acidification on fertilization and embryonic development of the ecologically important sea urchin Sterechinus neumayeri reared from fertilization in elevated temperature (+1.5°C and 3°C) and decreased pH (?0.3 and ?0.5 pH units) treatments. Fertilization using gametes from multiple males and females, to represent populations of spawners, was resilient to acidification at ambient temperature (0°C). At elevated temperatures, there was a negative interactive effect of temperature and pH on percentage of fertilization (11% reduction at 3°C). For cleavage stage embryos, there was a significant, but small reduction (6%) in the percentage of normal embryos at pH 7.5. For blastulae, a 10–11% decrease in normal development occurred in the +3°C treatments across all pH levels. Our results highlight the importance of considering the impacts of both temperature and pH in assessing the life history response of S. neumayeri in a changing polar ocean. While fertilization and development to the blastula stage were robust to levels of temperature and pH change predicted over coming decades, deleterious interactive effects were evident between these stressors at levels projected to occur by 2100 and beyond.     

No divergence in Cassiope tetragona: persistence of growth response along a latitudinal temperature gradient and under multi-year experimental warming

Background and Aims

The dwarf shrub Cassiope tetragona (Arctic bell-heather) is increasingly used for arctic climate reconstructions, the reliability of which depends on the existence of a linear climate–growth relationship. This relationship was examined over a high-arctic to sub-arctic temperature gradient and under multi-year artificial warming at a high-arctic site.

Methods

Growth chronologies of annual shoot length, as well as total leaf length, number of leaves and average leaf length per year, were constructed for three sites. Cassiope tetragona was sampled near its cold tolerance limit at Ny-Ålesund, Svalbard, at its assumed climatic optimum in Endalen, Svalbard, and near its European southern limit at Abisko, Sweden. Together these sites represent the entire temperature gradient of this species. Leaf life span was also determined. Each growing season from 2004 to 2010, 17 open top chambers (OTCs) were placed near Ny-Ålesund, thus increasing the daily mean temperatures by 1·23°C. At the end of the 2010 growing season, shoots were harvested from OTCs and control plots, and growth parameters were measured.

Key Results

All growth parameters, except average leaf length, exhibited a linear positive response (R² between 0·63 and 0·91) to mean July temperature over the temperature gradient. Average leaf life span was 1·4 years shorter in sub-arctic Sweden compared with arctic Svalbard. All growth parameters increased in response to the experimental warming; the leaf life span was, however, not significantly affected by OTC warming.

Conclusions

The linear July temperature–growth relationships, as well as the 7 year effect of experimental warming, confirm that the growth parameters annual shoot length, total leaf length and number of leaves per year can reliably be used for monitoring and reconstructing temperature changes. Furthermore, reconstructing July temperature from these parameters is not hampered by divergence.     

An IL28B genotype-based clinical prediction model for treatment of chronic hepatitis C

Background

Genetic variation in IL28B and other factors are associated with sustained virological response (SVR) after pegylated-interferon/ribavirin treatment for chronic hepatitis C (CHC). Using data from the HALT-C Trial, we developed a model to predict a patient''s probability of SVR based on IL28B genotype and clinical variables.

Methods

HALT-C enrolled patients with advanced CHC who had failed previous interferon-based treatment. Subjects were re-treated with pegylated-interferon/ribavirin during trial lead-in. We used step-wise logistic regression to calculate adjusted odds ratios (aOR) and create the predictive model. Leave-one-out cross-validation was used to predict a priori probabilities of SVR and determine area under the receiver operator characteristics curve (AUC).

Results

Among 646 HCV genotype 1-infected European American patients, 14.2% achieved SVR. IL28B rs12979860-CC genotype was the strongest predictor of SVR (aOR, 7.56; p<.0001); the model also included HCV RNA (log10 IU/ml), AST∶ALT ratio, Ishak fibrosis score and prior ribavirin treatment. For this model AUC was 78.5%, compared to 73.0% for a model restricted to the four clinical predictors and 60.0% for a model restricted to IL28B genotype (p<0.001). Subjects with a predicted probability of SVR <10% had an observed SVR rate of 3.8%; subjects with a predicted probability >10% (43.3% of subjects) had an SVR rate of 27.9% and accounted for 84.8% of subjects actually achieving SVR. To verify that consideration of both IL28B genotype and clinical variables is required for treatment decisions, we calculated AUC values from published data for the IDEAL Study.

Conclusion

A clinical prediction model based on IL28B genotype and clinical variables can yield useful individualized predictions of the probability of treatment success that could increase SVR rates and decrease the frequency of futile treatment among patients with CHC.     

The Gln32Lys polymorphism in HSP22 of Zhikong scallop Chlamys farreri is associated with heat tolerance

Background

Heat shock protein 22 is a member of small heat shock proteins with molecular chaperone activity. Though their multiple functions have been well characterized, there is no report about the association between the polymorphisms of HSP22 and heat tolerance.

Methodology

Three single nucleotide polymorphisms were identified in HSP22 from scallop Chlamys farreri (CfHSP22), and the +94 C-A locus was found to be nonsynonymous. Three genotypes at locus +94, A/A, A/C and C/C, were revealed by using Bi-PASA PCR analysis, and their frequencies were 19.5%, 27.6% and 52.9% in the heat resistant stock, while 9.3%, 17.4% and 73.3% in the heat susceptible stock, respectively. The frequency differences of the three genotypes were significant (P<0.05) between the two stocks. After incubating at 30°C for 84 h, the cumulative mortality of scallops with +94 C/C genotype and +94 A/C genotypes was 95% and 90%, respectively, which was significantly higher (P<0.01) than that of scallops with +94 A/A genotype (70%). The molecular chaperone activity of two His-tagged fusion proteins, rCfHSP22Q with +94 C/C genotype and rCfHSP22K with +94 A/A genotype were analyzed by testing the ability of protecting citrate synthase (CS) against thermal inactivation in vitro. After incubated with rCfHSP22Q or rCfHSP22K at 38°C for 1 h, the activity of CS lost 50% and 45%, and then recovered to 89% and 95% of the original activity following 1 h restoration at 22°C, respectively, indicating that the mutation from Gln to Lys at this site might have an impact on molecular chaperone activities of CfHSP22.

Conclusions

These results implied that the polymorphism at locus +94 of CfHSP22 was associated with heat tolerance of scallop, and the +94 A/A genotype could be a potential marker available in future selection of Zhikong scallop with heat tolerance.     

A dominant clone of Leptospira interrogans associated with an outbreak of human leptospirosis in Thailand

Background

A sustained outbreak of leptospirosis occurred in northeast Thailand between 1999 and 2003, the basis for which was unknown.

Methods and Findings

A prospective study was conducted between 2000 and 2005 to identify patients with leptospirosis presenting to Udon Thani Hospital in northeast Thailand, and to isolate the causative organisms from blood. A multilocus sequence typing scheme was developed to genotype these pathogenic Leptospira. Additional typing was performed for Leptospira isolated from human cases in other Thai provinces over the same period, and from rodents captured in the northeast during 2004. Sequence types (STs) were compared with those of Leptospira drawn from a reference collection. Twelve STs were identified among 101 isolates from patients in Udon Thani. One of these (ST34) accounted for 77 (76%) of isolates. ST34 was Leptospira interrogans, serovar Autumnalis. 86% of human Leptospira isolates from Udon Thani corresponded to ST34 in 2000/2001, but this figure fell to 56% by 2005 as the outbreak waned (p = 0.01). ST34 represented 17/24 (71%) of human isolates from other Thai provinces, and 7/8 (88%) rodent isolates. By contrast, 59 STs were found among 76 reference strains, indicating a much more diverse population genetic structure; ST34 was not identified in this collection.

Conclusions

Development of an MLST scheme for Leptospira interrogans revealed that a single ecologically successful pathogenic clone of L. interrogans predominated in the rodent population, and was associated with a sustained outbreak of human leptospirosis in Thailand.     

Baseline predictors of sputum culture conversion in pulmonary tuberculosis: importance of cavities, smoking, time to detection and W-Beijing genotype

Background

Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes.

Aim

To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis.

Design

Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable.

Results

113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype.

Conclusion

We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.     

Key genes as stress indicators in the ubiquitous diatom Skeletonema marinoi

Background

The dense phytoplankton blooms that characterize productive regions and seasons in the oceans are dominated, from high to low latitudes and from coast line to open ocean, by comparatively few, often cosmopolitan species of diatoms. These key dominant species may undergo dramatic changes due to global climate change.

Results

In order to identify molecular stress-indicators for the ubiquitous diatom species Skeletonema marinoi, we tested stress-related genes in different environmental conditions (i.e. nutrient starvation/depletion, CO₂-enrichment and combined effects of these stressors) using RT-qPCR. The data show that these stressors impact algal growth rate, inducing early aging and profound changes in expression levels of the genes of interest.

Conclusions

Most analyzed genes (e.g. antioxidant-related and aldehyde dehydrogenases) were strongly down-regulated which may indicate a strategy to avoid unnecessary over-investment in their respective proteins. By contrast, key genes were activated (e.g. HSPs, GOX) which may allow the diatom species to better cope with adverse conditions. We propose the use of this panel of genes as early bio-indicators of environmental stress factors in a changing ocean.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1574-5) contains supplementary material, which is available to authorized users.     

Contrasting patterns of coral bleaching susceptibility in 2010 suggest an adaptive response to thermal stress

Background

Coral bleaching events vary in severity, however, to date, the hierarchy of susceptibility to bleaching among coral taxa has been consistent over a broad geographic range and among bleaching episodes. Here we examine the extent of spatial and temporal variation in thermal tolerance among scleractinian coral taxa and between locations during the 2010 thermally induced, large-scale bleaching event in South East Asia.

Methodology/Principal Findings

Surveys to estimate the bleaching and mortality indices of coral genera were carried out at three locations with contrasting thermal and bleaching histories. Despite the magnitude of thermal stress being similar among locations in 2010, there was a remarkable contrast in the patterns of bleaching susceptibility. Comparisons of bleaching susceptibility within coral taxa and among locations revealed no significant differences between locations with similar thermal histories, but significant differences between locations with contrasting thermal histories (Friedman = 34.97; p<0.001). Bleaching was much less severe at locations that bleached during 1998, that had greater historical temperature variability and lower rates of warming. Remarkably, Acropora and Pocillopora, taxa that are typically highly susceptible, although among the most susceptible in Pulau Weh (Sumatra, Indonesia) where respectively, 94% and 87% of colonies died, were among the least susceptible in Singapore, where only 5% and 12% of colonies died.

Conclusions/Significance

The pattern of susceptibility among coral genera documented here is unprecedented. A parsimonious explanation for these results is that coral populations that bleached during the last major warming event in 1998 have adapted and/or acclimatised to thermal stress. These data also lend support to the hypothesis that corals in regions subject to more variable temperature regimes are more resistant to thermal stress than those in less variable environments.     

Serotonin transporter genotype (5-HTTLPR) predicts utilitarian moral judgments

Background

The psychological and neurobiological processes underlying moral judgment have been the focus of extensive recent research. Here we show that serotonin transporter (5-HTTLPR) genotype predicts responses to moral dilemmas featuring foreseen harm to an innocent.

Methodology/Principal Findings

Participants in this study judged the acceptability of actions that would unintentionally or intentionally harm an innocent victim in order to save others'' lives. An analysis of variance revealed a genotype × scenario interaction, F(2, 63) = 4.52, p = .02. Results showed that, relative to long allele homozygotes (LL), carriers of the short (S) allele showed particular reluctance to endorse utilitarian actions resulting in foreseen harm to an innocent individual. LL genotype participants rated perpetrating unintentional harm as more acceptable (M = 4.98, SEM = 0.20) than did SL genotype participants (M = 4.65, SEM = 0.20) or SS genotype participants (M = 4.29, SEM = 0.30). No group differences in moral judgments were observed in response to scenarios featuring intentional harm.

Conclusions/Significance

The results indicate that inherited variants in a genetic polymorphism that influences serotonin neurotransmission influence utilitarian moral judgments as well. This finding is interpreted in light of evidence that the S allele is associated with elevated emotional responsiveness.     

Developmental changes in the germinability, desiccation tolerance, hardseededness, and longevity of individual seeds of Trifolium ambiguum

Background and Aims

Using two parental clones of outcrossing Trifolium ambiguum as a potential model system, we examined how during seed development the maternal parent, number of seeds per pod, seed position within the pod, and pod position within the inflorescence influenced individual seed fresh weight, dry weight, water content, germinability, desiccation tolerance, hardseededness, and subsequent longevity of individual seeds.

Methods

Near simultaneous, manual reciprocal crosses were carried out between clonal lines for two experiments. Infructescences were harvested at intervals during seed development. Each individual seed was weighed and then used to determine dry weight or one of the physiological behaviour traits.

Key Results

Whilst population mass maturity was reached at 33–36 days after pollination (DAP), seed-to-seed variation in maximum seed dry weight, when it was achieved, and when maturation drying commenced, was considerable. Individual seeds acquired germinability between 14 and 44 DAP, desiccation tolerance between 30 and 40 DAP, and the capability to become hardseeded between 30 and 47 DAP. The time for viability to fall to 50 % (p₅₀) at 60 % relative humidity and 45 °C increased between 36 and 56 DAP, when the seed coats of most individuals had become dark orange, but declined thereafter. Individual seed f. wt at harvest did not correlate with air-dry storage survival period. Analysing survival data for cohorts of seeds reduced the standard deviation of the normal distribution of seed deaths in time, but no sub-population showed complete uniformity of survival period.

Conclusions

Variation in individual seed behaviours within a developing population is inherent and inevitable. In this outbreeder, there is significant variation in seed longevity which appears dependent on embryo genotype with little effect of maternal genotype or architectural factors.     

Association study on IL4, IL13 and IL4RA polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population

Background

The IL4, IL13, and IL4 receptor α chain (IL4RA) genes are candidate genes for atopic diseases. We hypothesized that the polymorphisms in these genes are associated with persistent allergic rhinitis (PER).

Objective

To investigate the association of the potential functional polymorphisms in IL4, IL13, and IL4RA with PER induced by house dust mites in a Chinese population.

Methods

Using the TaqMan method, we genotyped six single nucleotide polymorphisms (SNPs) including C-590T in IL4, C-1055T and Arg130Gln in IL13, and Ile50Val, Ser478Pro and Gln551Arg in IL4RA, in a case-control study of 265 patients with PER and 275 healthy controls.

Results

We found that the CT/CC genotypes in IL4 C-590T were associated with a significantly decreased risk of mite-sensitized PER [adjusted odds ratio (OR)  = 0.64, 95% confidence interval (CI) 0.45–0.92], compared to the TT genotype. Furthermore, PER patients with CT/CC genotypes had significantly lower serum levels of total IgE than those with TT genotype (P = 0.001). However, there was no significant association of the IL13 and IL4RA polymorphisms with mite-sensitized PER (P>0.05).

Conclusions

Our results suggest that the C-590T polymorphism in IL4 may contribute to the susceptibility to mite-sensitized PER in a Chinese population.     

Impact of IL28B-related single nucleotide polymorphisms on liver histopathology in chronic hepatitis C genotype 2 and 3

Background and Aims

Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of HCV infection as well as outcome following peginterferon and ribavirin therapy among HCV genotype 1 infected patients. The present study aimed to evaluate the impact of IL28B SNP variability on liver histology in the context of a phase III treatment trial (NORDynamIC) for treatment-naïve patients with chronic HCV genotype 2 or 3 infection, where pretreatment liver biopsies were mandatory.

Methods

Three hundred and thirty-nine Caucasian patients had samples available for IL28B genotyping (rs12979860) of whom 314 had pretreatment liver biopsies that were evaluated using the Ishak protocol, allowing for detailed grading and staging of liver histopathology.

Results

IL28B CC_rs12979860 genotype in HCV genotype 3 infected patients was associated with higher ALT levels (p<0.0001), higher AST to platelet ratio index (APRI; p = 0.001), and higher baseline viral load (p<0.0001) as compared to patients with the CT or TT genotypes. Additionally the CC_rs12979860 genotype entailed more pronounced portal inflammation (p = 0.02) and steatosis (p = 0.03). None of these associations were noted among HCV genotype 2 infected patients.

Conclusion

This study shows that the CC_rs12979860 SNP is associated with more pronounced liver histopathology in patients chronically infected with HCV genotype 3, which may be secondary to higher viral load. The finding that IL28B variability did not impact on liver pathology or viral load among genotype 2 infected patients implies that IL28B may differentially regulate the course of genotype 2 and 3 infection.     

Feasibility of bispectral index-guided propofol infusion for flexible bronchoscopy sedation: a randomized controlled trial

Objectives

There are safety issues associated with propofol use for flexible bronchoscopy (FB). The bispectral index (BIS) correlates well with the level of consciousness. The aim of this study was to show that BIS-guided propofol infusion is safe and may provide better sedation, benefiting the patients and bronchoscopists.

Methods

After administering alfentanil bolus, 500 patients were randomized to either propofol infusion titrated to a BIS level of 65-75 (study group) or incremental midazolam bolus based on clinical judgment to achieve moderate sedation. The primary endpoint was safety, while the secondary endpoints were recovery time, patient tolerance, and cooperation.

Results

The proportion of patients with hypoxemia or hypotensive events were not different in the 2 groups (study vs. control groups: 39.9% vs. 35.7%, p = 0.340; 7.4% vs. 4.4%, p = 0.159, respectively). The mean lowest blood pressure was lower in the study group. Logistic regression revealed male gender, higher American Society of Anesthesiologists physical status, and electrocautery were associated with hypoxemia, whereas lower propofol dose for induction was associated with hypotension in the study group. The study group had better global tolerance (p<0.001), less procedural interference by movement or cough (13.6% vs. 36.1%, p<0.001; 30.0% vs. 44.2%, p = 0.001, respectively), and shorter time to orientation and ambulation (11.7±10.2 min vs. 29.7±26.8 min, p<0.001; 30.0±18.2 min vs. 55.7±40.6 min, p<0.001, respectively) compared to the control group.

Conclusions

BIS-guided propofol infusion combined with alfentanil for FB sedation provides excellent patient tolerance, with fast recovery and less procedure interference.

Trial Registration

ClinicalTrials. gov {"type":"clinical-trial","attrs":{"text":"NCT00789815","term_id":"NCT00789815"}}NCT00789815