Interstrains comparison of the antimicrobial effect and mode of action of a Vietnamese Cinnamomum cassia essential oil from leaves and its principal component against Listeria monocytogenes.

The antibacterial activity of a Cinnamomum cassia essential oil (EO) and of its main component trans-cinnamaldehyde (90% w/w) was examined against five Listeria monocytogenes strains. The minimal inhibitory concentrations (MICs) of C. cassia EO against the five L. monocytogenes strains were identical (250 µg ml-1 ), while the minimal bactericidal concentrations (MBCs) ranged between 800 and 1200 µg ml-1 . In order to study if this EO and trans-cinnamaldehyde altered the five strains at the membrane level, fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene (DPH) was measured in presence of different concentrations (1/2MIC, MIC, 2MIC) of these antibacterial agents. A concentration-dependent increase of fluorescence anisotropy of DPH in their presence reflecting a rigidification of the membrane was observed for the five strains. This modification of the membrane fluidity was associated with a perturbation of the selective membrane permeability, as a perturbation of the gradient between intracellular and extracellular pH was also observed.

Time to viral suppression is not related to achievement of SVR12 in HCV GT1-infected patients treated with ombitasvir/paritaprevir/ritonavir and dasabuvir with or without ribavirin.

High rates of sustained virologic response at post-treatment week 12 (SVR12) were achieved in six phase 3 trials of ombitasvir (OBV, an NS5A inhibitor), paritaprevir (an NS3/4A protease inhibitor) co-dosed with ritonavir (PTV/r) + dasabuvir (DSV, an NS5B RNA polymerase inhibitor) (ie, 3D regimen) with or without ribavirin (RBV) in adults with chronic genotype (GT) 1 hepatitis C virus (HCV) infection. We assessed whether time to first HCV RNA value below the lower limit of quantification in patients with and without cirrhosis was associated with achievement of SVR12. Data were analysed from GT1-infected patients enrolled in six phase 3 studies of 3D ± RBV. Patients who experienced non-virologic failure were excluded from analysis. HCV RNA was determined using the Roche COBAS TaqMan RT-PCR assay (lower limit of quantification, LLOQ =25 IU/mL). SVR12 was analysed by week of first HCV RNA suppression, defined as HCV RNA

Fate and ecotoxicological impact of new generation herbicides from the triketone family: An overview to assess the environmental risks.

Triketones, derived chemically from a natural phytotoxin (leptospermone), are a good example of allelochemicals as lead molecules for the development of new herbicides. Targeting a new and key enzyme involved in carotenoid biosynthesis, these latest-generation herbicides (sulcotrione, mesotrione and tembotrione) were designed to be eco-friendly and commercialized fifteen-twenty years ago. The mechanisms controlling their fate in different ecological niches as well as their toxicity and impact on different organisms or ecosystems are still under investigation. This review combines an overview of the results published in the literature on ß-triketones and more specifically, on the commercially-available herbicides and includes new results obtained in our interdisciplinary study aiming to understand all the processes involved (i) in their transfer from the soil to the connected aquatic compartments, (ii) in their transformation by photochemical and biological mechanisms but also to evaluate (iii) the impacts of the parent molecules and their transformation products on various target and non-target organisms (aquatic microorganisms, plants, soil microbial communities). Analysis of all the data on the fate and impact of these molecules, used pure, as formulation or in cocktails, give an overall guide for the assessment of their environmental risks.

Epigenetic analysis of the IFNλ3 gene identifies a novel marker for response to therapy in HCV-infected subjects.

Chronic hepatitis C virus (HCV) infection is characterized by high interindividual variability in response to pegylated interferon and ribavirin. A genetic polymorphism on chromosome 19 (rs12979860) upstream of interferon-λ3 (IFNλ3) is associated with a twofold change in sustained virologic response rate after 48 weeks of treatment with pegylated interferon/ribavirin in HCV genotype 1 (GT1) treatment-naïve patients. We conducted epigenetic analysis on the IFNλ3 promoter to investigate whether DNA methylation is associated with response to HCV therapy. DNA samples from HCV GT1-infected subjects receiving an interferon-free paritaprevir-containing combination regimen (N=540) and from HCV-uninfected, healthy controls (N=124) were analysed for IFNλ3 methylation levels. Methylation was strongly associated with rs12979860 allele status whether adjusting for HCV status (r=65.0%, 95% CI: [60.2%, 69.5%]), or not (r=64.4%), both with P<2.2×10-16 . In HCV GT1-infected subjects, C/C genotypes had significantly lower methylation levels relative to C/T or T/T genotypes (P<1×10-14 ), with each T allele resulting in a nine-unit increase in mean methylation level. Methylation levels did not correlate with response in subjects treated for 12 or 24 weeks. However, non-C/C subjects with higher methylation levels were more likely to relapse when treatment duration was 8 weeks. This analysis suggests that methylation status of the IFNλ3 promoter region may be a useful parameter that identifies patients more likely to relapse following HCV therapy; however, continuing therapy for a sufficient duration can overcome this difference. These findings may provide mechanistic insight into the role of IFNλ3 genetic variants in HCV treatment response.

Molecular data reveal a cryptic species within the Culex pipiens mosquito complex.

The Culex pipiens mosquito complex is a group of evolutionarily closely related species including C. pipiens and Culex quinquefasciatus, both infected by the cytoplasmically inherited Wolbachia symbiont. A Wolbachia-uninfected population of C. pipiens was however described in South Africa and was recently proposed to represent a cryptic species. In this study, we reconsidered the existence of this species by undertaking an extensive screening for the presence of Wolbachia-uninfected C. pipiens specimens and by characterizing their genetic relatedness with known members of the complex. We first report on the presence of Wolbachia-uninfected specimens in several breeding sites. We next confirm that these uninfected specimens unambiguously belong to the C. pipiens complex. Remarkably, all uninfected specimens harbour mitochondrial haplotypes that are either novel or identical to those previously found in South Africa. In all cases, these mitochondrial haplotypes are closely related, but different, to those found in other C. pipiens complex members known to be infected by Wolbachia. Altogether, these results corroborate the presence of a widespread cryptic species within the C. pipiens species complex. The potential role of this cryptic C. pipiens species in the transmission of pathogens remains however to be determined. The designation 'Culex juppi nov. sp.' is proposed for this mosquito species.

Serum miR-122 may serve as a biomarker for response to direct acting antivirals: effect of paritaprevir/R with dasabuvir or ombitasvir on miR-122 in HCV-infected subjects.

Circulating microRNAs (miRNA) have been intensely investigated as biomarkers in disease and therapy. Several studies have identified miR-122 as an important regulator of HCV replication. The effect of new therapies that directly target the HCV replication life cycle on circulating microRNA levels has not been elucidated. We performed expression profiling of circulating miRNA in serum in subjects treated with HCV direct-acting antiviral agents (DAAs). Serum miRNA levels were evaluated from two studies in HCV GT1-infected treatment-naïve subjects and prior nonresponders to pegylated interferon (pegIFN) and ribavirin (RBV) who received paritaprevir/ritonavir + dasabuvir + RBV for 12 weeks, and in treatment-naïve genotype (GT)1-3-infected subjects who received paritaprevir/ritonavir + ombitasvir ± RBV for 12 weeks. Over 100 different miRNA species were detected in serum. Of these, levels of miR-122 showed the most consistent change in response to treatment across all HCV genotypes. In all subjects, miR-122 showed an average four-fold reduction between baseline and week 2, and remained below baseline through post-treatment week 12 in subjects who achieved sustained virological response. In contrast, in subjects who did not achieve SVR, miR-122 levels began to return to baseline levels after the second week of treatment. The change in miR-122 levels was similar across genotypes, and was comparable with or without RBV. This is the first report comparing expression levels of circulating miRNA in HCV GT1-3 subjects treated with IFN-free combinations of DAAs. The results suggest that serum levels of miR-122 are reduced following treatment in subjects who achieve SVR, and correlate with HCV RNA levels across genotypes.

Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship.

Magnetization transfer imaging in premanifest and manifest huntington disease: a 2-year follow-up.

BACKGROUND AND PURPOSE: MTI is a quantitative MR imaging technique that has recently demonstrated structural integrity differences between controls and patients with HD. Potentially, MTI can be used as a biomarker for monitoring disease progression. To establish the value of MTI as a biomarker, we aimed to examine the change in these measures during the course of HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 25 controls, 21 premanifest gene carriers, and 21 patients with manifest HD participated at baseline and during a 2-year follow-up visit. Brain segmentation of the cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed by using the automated tools FAST and FIRST in FSL. Individual MTR values were calculated from these regions, and MTR histograms were constructed. RESULTS: In the premanifest HD group stage "far from disease onset," a significant increase in MTR peak height of the putamen was observed with time. During the manifest HD stage, neither the mean MTR nor the MTR peak height showed a significant change during a 2-year follow-up. CONCLUSIONS: MTI-derived measures are not suitable for monitoring in Huntington disease during a 2-year period because there was no decrease in structural integrity detected in any of the manifest HD groups longitudinally. The finding of increased putaminal MTR peak height in the premanifest far from disease onset group could relate to a predegenerative process, compensatory mechanisms, or aberrant development but should be interpreted with caution until future studies confirm this finding.

Magnetization transfer imaging in premanifest and manifest Huntington disease.

BACKGROUND AND PURPOSE: MTI has the potential to detect abnormalities in normal-appearing white and gray matter on conventional MR imaging. Early detection methods and disease progression markers are needed in HD research. Therefore, we investigated MTI parameters and their clinical correlates in premanifest and manifest HD. MATERIALS AND METHODS: From the Leiden TRACK-HD study, 78 participants (28 controls, 25 PMGC, 25 MHD) were included. Brain segmentation of cortical gray matter, white matter, caudate nucleus, putamen, pallidum, thalamus, amygdala, and hippocampus was performed using FSL's automated tools FAST and FIRST. Individual MTR values were calculated from these regions and MTR histograms constructed. Regression analysis of MTR measures from all gene carriers with clinical measures was performed. RESULTS: MTR peak height was reduced in both cortical gray (P = .01) and white matter (P = .006) in manifest HD compared with controls. Mean MTR was also reduced in cortical gray matter (P = .01) and showed a trend in white matter (P = .052). Deep gray matter structures showed a uniform pattern of reduced MTR values (P < .05). No differences between premanifest gene carriers and controls were found. MTR values correlated with disease burden and motor and cognitive impairment. CONCLUSIONS: Throughout the brain, disturbances in MTI parameters are apparent in early HD and are homogeneous across white and gray matter. The correlation of MTI with clinical measures indicates the potential to act as a disease monitor in clinical trials. However, our study does not provide evidence for MTI as a marker in premanifest HD.

Deficient sustained attention to response task and P300 characteristics in early Huntington's disease.

Evidence for the extent and nature of attentional impairment in premanifest and manifest Huntington's disease (HD) is inconsistent. Understanding such impairments may help to better understand early functional changes in HD and could have consequences concerning care for HD patients. We investigated attentional control in both early and premanifest HD. We studied 17 early HD subjects (mean age: 51 years), 12 premanifest HD subjects (mean age: 43 years), and 15 healthy controls (mean age: 51 years), using the sustained attention to response task (SART), a simple Go/No-go test reflecting attentional and inhibitory processes through reaction time (RT) and error rates. Simultaneously recorded EEG yielded P300 amplitudes and latencies. The early HD group made more Go errors (p < 0.001) and reacted slower (p < 0.005) than the other groups. The RT pattern during the SART was remarkably different for early HD subjects compared to the other two groups (p < 0.005), apparent as significant post-error slowing. P300 data showed that for early HD the No-go amplitude was lower than for the other two groups (p < 0.05). Subjects with early HD showed a reduced capacity to effectively control attention. They proved unable to resume the task directly after having made an error, and need more time to return to pre-error performance levels. No attentional control deficits were found for the premanifest HD group.

Shape analysis of subcortical nuclei in Huntington's disease, global versus local atrophy--results from the TRACK-HD study.

Huntington's disease (HD) is characterized by brain atrophy. Localized atrophy of a specific structure could potentially be a more sensitive biomarker reflecting neuropathologic changes rather than global volume variation. We examined 90 TRACK-HD participants of which 30 were premanifest HD, 30 were manifest HD and 30 were controls. Using FMRIB's Integrated Registration and Segmentation Tool, segmentations were obtained for the pallidum, caudate nucleus, putamen, thalamus, accumbens nucleus, amygdala, and hippocampus and overall volumes were calculated. A point distribution model of each structure was obtained using Growing and Adaptive Meshes. Permutation testing between groups was performed to detect local displacement in shape between groups. In premanifest HD overall volume loss occurred in the putamen, accumbens and caudate nucleus. Overall volume reductions in manifest HD were found in all subcortical structures, except the amygdala, as compared to controls. In premanifest HD shape analysis showed small areas of displacement in the putamen, pallidum, accumbens and caudate nucleus. When the premanifest group was split into two groups according to predicted disease onset, the premanifest HD group close to expected disease onset showed more pronounced displacements in caudate nucleus and putamen compared to premanifest HD far from disease onset or the total premanifest group. Analysis of shape in manifest HD showed widespread shape differences, most prominently in the caudal part of the accumbens nucleus, body of the caudate nucleus, putamen and dorsal part of the pallidum. We conclude that shape analysis provides new insights in localized intrastructural atrophy patterns in HD, but can also potentially serve as specific target areas for disease tracking.

The hepatitis C virus minigenome: a new cellular model for studying viral replication.

The cellular models used usually to study hepatitis C virus replication involve coupling between translation and replication. Because this linkage makes detailed analyses difficult a new cellular model was developed where replication is rendered independent of translation. The RNA replication was studied using RNA minigenomes where the reporter gene was flanked by the two untranslated regions of HCV. It was shown that these RNA minigenomes could be stably replicated into Huh7 cells expressing the HCV replication complex. This was obtained either by constitutively expressing the non-structural proteins into Huh7 hepatoma cells or by using Huh7 cells harboring replicons.

Haemonchus contortus egg excretion and female length reduction in sheep previously infected with Oestrus ovis (Diptera: Oestridae) larvae.

Mixed parasitic infection of animals is a common phenomenon in nature. The existence of one species often positively or negatively influences the survival of the other. Our experimental study was started with the objectives to demonstrate the interaction of Haemonchus contortus and Oestrus ovis in relation to cellular and humoral immune responses in sheep. Twenty-two sheep of Tarasconnais breed (France) were divided into four groups (O, OH, H and C) of five or six animals. Group O and OH received 5 weekly consecutive inoculations with O. ovis L1 larvae (total = 82 L1) in the first phase of the experiment between days 0 and 28. On the second phase, groups OH and H received 5000 L3 of H. contortus on day 48 while group C served as our control throughout the experimental period. Parasitological, haematological, serological and histopathological examinations were made according to standard procedures and all animals were slaughtered at day 95. There was no significant variation in the number and degree of development of O. ovis larvae between the two infected groups. Furthermore, in tissues examined in the upper respiratory tract (nasal septum, turbinate, ethmoide and sinus), group O and OH has responded similarly on the basis of cellular inflammatory responses (blood and tissue eosinophils, mast cells and globule leucocytes (GL)) and serum antibody responses against the nasal bots. This may indicate that the presence of H. contortus in the abomasa of group OH had no marked influence over the development of O. ovis larvae in the upper respiratory tract. On the other hand, we have observed a significantly lower H. contortus female worm length, fecal egg count (FEC) and in utero egg count in animals harbouring the nasal bot (OH) than in the mono-infected group (H). This was significantly associated with higher blood eosinophilia, higher packed cell volume (PCV) and increased number of tissue eosinophils and globule leucocytes. We conclude that, the establishment of O. ovis larvae in the upper respiratory tract has initiated higher inflammatory cellular activity in group OH there by influencing the development and fecundity of H. contortus in the abomasum.

Gastrointestinal complications following cardiac surgery. An analysis of 1477 cardiac surgery patients.

OBJECTIVE: To determine preoperative and perioperative risk factors for gastrointestinal (GI) complications following cardiac surgery. DESIGN: A database including records of patients who underwent cardiac surgery was reviewed, with univariate analysis of several variables thought to be relevant to GI complications. Using a risk-adjusted model, preoperative stratification was used to fit a logistic regression model including operative features. SETTING AND PATIENTS: All patients undergoing cardiac surgery from January 1, 1991, to December 31, 1994, at a university-affiliated teaching hospital. MAIN OUTCOME MEASURES: Incidence of GI complications, postoperative mortality, length of hospital stay, and relative risk of GI complications based on multivariate analyses. RESULTS: Gastrointestinal complications occurred in 2.1% of patients and had an associated mortality of 19.4%; this was higher than the mortality in patients without GI complications (4.1%; P < .001). Length of hospital stay was significantly longer in patients with GI complications (43 vs 13.4 days; P < .001). In patients who underwent coronary artery bypass grafting only, cardiopulmonary bypass time was significantly longer in patients with GI complications (166 vs 138 minutes; P = .004). In patients who underwent valve replacement, bypass time was not associated with GI complications. Use of a left internal mammary artery graft was associated with a lower incidence of GI complications. CONCLUSIONS: Patients who have GI complications after cardiac surgery have a higher mortality and a longer hospital stay. The use of a left internal mammary artery seems to have a protective effect against GI complications. Based on these observations, patients may be stratified into low-, medium-, and high-risk groups.

[Head-up tilt test in healthy asymptomatic patients]. / Tilt test en sujetos sanos asintomáticos.

The head-up tilt test has demonstrated to be useful in the study of patients with syncope of unknown origin for the diagnosis of neurocardiogenic syncope. Several publications have described different methods, with different results in cases as well as in controls. We performed a prospective study in a group of normal subjects in order to evaluate the methodology used in our population and to establish its specificity. A positive test was defined as the presence of syncope or presyncope and hypotension. The examination was carried out on a tilt table, five minutes at 0 degree, then at 70 degrees during 20 min. In the absence of syncope or presyncope an i.v. infusion of isoproterenol was started afterwards in order to increase the heart rate 30-50% over the baseline values and administered during 20 min at 70 degrees. Twenty one volunteers (14 male and 7 women; mean age 26.7 +/- 3.5 years; range: 21-33 years) and body mass index 23.4 +/- 2.2 kg/m2 were examined. Mean dose of isoproterenol was 3.1 +/- 0.9 micrograms/min (3.4 +/- 1.1 in men and 2.6 +/- 0.7 micrograms/min in women, NS). During the phase without isoproterenol no subject developed hemodynamic alterations neither symptoms. One volunteer (4.8%) developed presyncope and systemic hypotension (52/28 mm Hg) accompanied with nodal rhythm after 14 min of isoproterenol at 70 degrees, and his examination was discontinued, with immediate recovery. Three other subjects developed asymptomatic transient nodal rhythm during the phase with isoproterenol and recovered spontaneously. No other complications were observed. It is concluded that head-up tilt test with isoproterenol at 70 degrees, with the used doses and heart rate increments, is highly specific (95%) to establish the diagnosis of a neurocardiogenic syncope.

A comparison of four severity-adjusted models to predict mortality after coronary artery bypass graft surgery.

OBJECTIVE: To assess the validity of four severity-adjusted models to predict mortality following coronary artery bypass graft surgery by using an independent surgical database. DESIGN: A prospective observational study wherein predicted mortality for each patient was obtained by using four different published severity-adjusted models. SETTING: A university-affiliated teaching community hospital. PATIENTS: Eight hundred sixty-eight consecutive patients who underwent coronary artery bypass graft surgery without accompanying valve or aneurysm repair during the period from 1991 to 1993. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Predicted mortality rates for each model were obtained by averaging individual patient predictions and were compared with actual morality rates. We assessed the accuracy of overall prediction for the total series, as well as compared individual patient predictions created by each model. The discrimination of models was assessed with receiver operating characteristic curves and the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The observed crude mortality rate was 3.7%. The predicted mortality rate ranged from 2.8% to 9.2%, despite relatively good discrimination by the models (area under the receiver operating characteristic curve, 0.70 to 0.74). The individual patient mortality predicted by different models varied by as much as a ninefold difference. CONCLUSIONS: The currently used coronary artery bypass graft predictive models, although generally accurate, have significant shortcomings and should be used with caution. The predicted mortality rate following coronary artery bypass graft surgery varied by a factor of 3.3 from lowest to highest, making the choice of model a critical factor when assessing outcome. The use of these models for individual patient risk estimations is risky because of the marked discrepancies in individual predictions created by each model.

Field study on exposure and health effects of an organophosphate pesticide for maintaining registration in the Philippines.

To support the continued use and the registration of monocrotophos, a field study was conducted at Calauan, Laguna, The Philippines, to assess exposure and the resulting health risk to 21 spraymen applying monocrotophos to rice crop by knapsack spraying during 3 consecutive days. The findings of the study were as follows: exposure of uncovered hands and of the skin of the back to the concentrate was visually observed during the filling, and respectively loading operations; During spraying exposure from airborne diluted formulation occurred; in addition contamination of the lower parts of the body took place because of direct contact with the sprayed crop; Determination of the amount of the urinary metabolite dimethylphosphate excreted in 24 hours urine samples demonstrated absorption of monocrotophos into the body of the spraymen. The half-life of elimination of the urinary metabolite from the body was on average 18 hours; No clinically significant inhibitions of whole blood or red blood cell cholinesterase activities were found, i.e., 30% below baseline values. However, 8 of 21 spraymen had plasma cholinesterase levels below 50% of baseline values;--No acute adverse health effects associated with the application of monocrotophos were observed, which was in accordance with the absence of clinically significant cholinesterase depressions. The conclusion of the study was that the use of monocrotophos under prevailing typical conditions in the Philippines, which varies from a frequency of one application per season to a maximum of 3 applications each on 3 consecutive days per week, and where label safety instructions are not necessarily observed, is not expected to pose an acute health risk under the prevailing conditions and practices, which includes filling, spraying and cleaning activities. From the experience in this study it is clear that proper spraying technique and adequate use of personal protection will significantly reduce exposure. As such a reduction is highly recommendable, advice on proper spray procedures and adequate personal protection has been reinforced.

Detection of PR-b proteins in tobacco roots infected with Chalara elegans.

All previous studies on pathogenesis-related (b) protein (PR-b) induction in tobacco have been carried out on leaves or callus tissue. This paper reports the production of PR-b proteins also in roots of tobacco plants (Nicotiana tabacum cv. Xanthi NC) infected with Chalara elegans. Antiserum against PR-b1 reacted with PR-b1, PR-b2 and PR-b3 and gave the same pattern of reaction as for leaves. Antiserum against PR-b5 revealed the presence of PR-b4, PR-b5 and, very weakly, PR-b6 which have been shown to be beta-1,3 glucanases. Antiserum against PR-b7 reacted with both PR-b7 and PR-b8 which are chitinases.

The chemical induction of PR (b) proteins and resistance to TMV infection in tobacco.

Aspirin injected into Xanthi-nc tobacco leaves induces the production of PR protein and resistance to TMV. The concentration of PR protein and resistance increases with increasing aspirin concentration, up to a plateau. 2-Thiouracil and dioxohexahydrotriazine also induce PR protein when injected into tobacco leaves. Barium and manganese salts induced PR protein, but those of eight other cations did not. Certain salts were phytotoxic but did not induce PR protein, confirming that the production of PR protein is not a non-specific stress response.