Pharmacological analysis of the feeding response of codling moth (Cydia pomonella; Lepidoptera: Tortricidae) neonates to bitter compounds

Feeding in codling moth neonate caterpillars was inhibited by 0.67 mM and 2.24 mM concentrations of denatonium benzoate. This inhibitory effect was abolished by phospholipase C inhibitor, U-73122 and the phosphodiesterase inhibitor, Rolipram. Quinine and quinidine did not have inhibitory effects at concentrations as high as 1.64 mM and 0.43 mM, respectively. The inhibitory effect of denatonium was partially reversed in the presence of the calcium ion chelator, EGTA, at concentrations ranging from 2.5 μM to 250 μM. These results indicate that transduction of the taste of denatonium in codling moth neonates relies on signalling pathways that involve phospholipase C, phosphodiesterase and calcium ion influx into cells

Artemisia annua extracts, artemisinin and 1,8-cineole, prevent fruit infestation by a major, cosmopolitan pest of apples

Context: Extracts of Artemisia annua (L.) (Asteraceae) and artemisinins are used for treatment of malaria, parasitic infections and have potent anticancer properties in cell lines. Eucalyptus oil and 1,8-cineole have antimicrobial, immune-stimulatory, anti-inflammatory, antioxidant, analgesic, and spasmolytic effects. Codling moth, Cydia pomonella, (L.) (Tortricidae), is a major cosmopolitan pest of the apple, potentially causing damage translating to 40 billion US dollars per year, globally. Currently used control measures are either hazardous to agricultural workers and harmful to environment, or ineffective. The potential of plant-derived semiochemicals for codling moth control is heavily understudied. Objective: This study evaluated the potential of A. annua extracts, and two chemicals that this plant contains, artemisinin and 1,8-cineole, for preventing apple feeding and infestation by neonate Cydia pomonella larvae. Methods: We studied effects of A. annua extracts, artemisinin and 1,8-cineole on apple infestation by neonate codling moth larvae using fruit choice assay in laboratory experiments. Preference of fruit treated with test solutions versus fruit treated with solvent was recorded and analyzed. Results: Crude A. annua extracts prevented fruit feeding at 1, 3, and 10 mg/ml. Artemisinin had feeding deterrent effects at 10 and 30 mg/ml, and 1,8-cineole at 100 and 300 mg/ml. Discussion and Conclusions: A. annua contains chemicals that prevent apple infestation by codling moth neonates. Artemisinin and 1,8-cineole are among them, but there are other, polar constituents of A. annua, which have similar effects. There is a potential of using our findings in codling moth control and production of codling moth-resistant apples

Recruitment challenges in MRI studies of acute intracerebral haemorrhage: experience from the TICH-2 MRI substudy

BACKGROUND AND AIMS Magnetic Resonance Imaging (MRI) is widely used in clinical practice and in trials for ischaemic stroke; however, relatively few large multicentre trials for intracerebral haemorrhage have used MRI. We describe the main recruitment challenges faced in the TICH-2 MRI substudy, which is nested within TICH-2, a multi-centre randomised placebo-controlled trial of tranexamic acid in intracerebral haemorrhage (ISRCTN93732214). METHOD TICH-2 participants at recruiting centres were eligible for the substudy. Centres were asked to record, if applicable, the reason for non-recruitment. The recruitment window was day 2 to day 14 post-randomisation. RESULTS Figure 1 shows the distribution of reasons for non-recruitment (N=169). Clinical instability was the main reason for non-recruitment, accounting for 34.3% of the cases. The mean NIHSS scores (as per TICH-2 protocol) for unrecruited patients classified as clinically unstable were 19 (range 5-32,N=57), 21 (range 0-40,N=51) and 20 (range 1-38,N=37) for baseline, day 2 and day 7 post-randomisation, respectively. In contrast, for recruited patients (N=142) the mean scores were 10 (range 0-28,N=141), 8 (range 0-26,N=139) and 8 (range 0-31,N=132). Other important factors for non-recruitment include difficulty obtaining consent, patient refusal, claustrophobia and transfer to other hospitals. CONCLUSION Clinical instability in intracerebral haemorrhage poses a challenge for recruitment into MRI studies. This, and other factors, should be taken into consideration when designing clinical trials of intracerebral haemorrhage involving MRI

Quantitative CT radiomics-based models for prediction of haematoma expansion and poor functional outcome in primary intracerebral haemorrhage

Objectives: To test radiomics-based features extracted from noncontrast CT of patients with spontaneous intracerebral haemorrhage for prediction of haematoma expansion and poor functional outcome and compare them with radiological signs and clinical factors.Materials and methods: Seven hundred fifty-four radiomics-based features were extracted from 1732 scans derived from the TICH-2 multicentre clinical trial. Features were harmonised and a correlation-based feature selection was applied. Different elastic-net parameterisations were tested to assess the predictive performance of the selected radiomics-based features using grid optimisation. For comparison, the same procedure was run using radiological signs and clinical factors separately. Models trained with radiomics-based features combined with radiological signs or clinical factors were tested. Predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) score.Results: The optimal radiomics-based model showed an AUC of 0.693 for haematoma expansion and an AUC of 0.783 for poor functional outcome. Models with radiological signs alone yielded substantial reductions in sensitivity. Combining radiomics-based features and radiological signs did not provide any improvement over radiomics-based features alone. Models with clinical factors had similar performance compared to using radiomics-based features, albeit with low sensitivity for haematoma expansion. Performance of radiomics-based features was boosted by incorporating clinical factors, with time from onset to scan and age being the most important contributors for haematoma expansion and poor functional outcome prediction, respectively.Conclusion: Radiomics-based features perform better than radiological signs and similarly to clinical factors on the prediction of haematoma expansion and poor functional outcome. Moreover, combining radiomics-based features with clinical factors improves their performance.Key points: Linear models based on CT radiomics-based features perform better than radiological signs on the prediction of haematoma expansion and poor functional outcome in the context of intracerebral haemorrhage. Linear models based on CT radiomics-based features perform similarly to clinical factors known to be good predictors. However, combining these clinical factors with radiomics-based features increases their predictive performance

Automated segmentation of haematoma and perihaematomal oedema in MRI of acute spontaneous intracerebral haemorrhage

BackgroundSpontaneous intracerebral haemorrhage (SICH) is a common condition with high morbidity and mortality. Segmentation of haematoma and perihaematoma oedema on medical images provides quantitative outcome measures for clinical trials and may provide important markers of prognosis in people with SICH.MethodsWe take advantage of improved contrast seen on magnetic resonance (MR) images of patients with acute and early subacute SICH and introduce an automated algorithm for haematoma and oedema segmentation from these images. To our knowledge, there is no previously proposed segmentation technique for SICH that utilises MR images directly. The method is based on shape and intensity analysis for haematoma segmentation and voxel-wise dynamic thresholding of hyper-intensities for oedema segmentation.ResultsUsing Dice scores to measure segmentation overlaps between labellings yielded by the proposed algorithm and five different expert raters on 18 patients, we observe that our technique achieves overlap scores that are very similar to those obtained by pairwise expert rater comparison. A further comparison between the proposed method and a state-of-the-art Deep Learning segmentation on a separate set of 32 manually annotated subjects confirms the proposed method can achieve comparable results with very mild computational burden and in a completely training-free and unsupervised way.ConclusionOur technique can be a computationally light and effective way to automatically delineate haematoma and oedema extent directly from MR images. Thus, with increasing use of MR images clinically after intracerebral haemorrhage this technique has the potential to inform clinical practice in the future

Multiparametric cerebellar imaging and clinical phenotype in childhood ataxia telangiectasia

BackgroundAtaxia Telangiectasia (A-T) is an inherited multisystem disorder with cerebellar neurodegeneration. The relationships between imaging metrics of cerebellar health and neurological function across childhood in A-T are unknown, but may be important for determining timing and impact of therapeutic interventions.PurposeTo test the hypothesis that abnormalities of cerebellar structure, physiology and cellular health occur in childhood A-T and correlate with neurological disability, we performed multiparametric cerebellar MRI and establish associations with disease status in childhood A-T.MethodsProspective cross-sectional observational study. 22 young people (9 females / 13 males, age 6.6-17.8 years) with A-T and 24 matched healthy controls underwent 3-Tesla MRI with volumetric, diffusion and proton spectroscopic acquisitions. Participants with A-T underwent structured neurological assessment, and expression / activity of ataxia-telangiectasia mutated (ATM) kinase were recorded.ResultsAtaxia-telangiectasia participants had cerebellar volume loss (fractional total cerebellar volume: 5.3% vs 8.7%, P less than 0.0005, fractional 4th ventricular volumes: 0.19% vs 0.13%, P less than 0.0005), that progressed with age (fractional cerebellar volumes, r=-0.66, P=0.001), different from the control group (t=-4.88, P less than 0.0005). The relationship between cerebellar volume and age was similar for A-T participants with absent ATM kinase production and those producing non-functioning ATM kinase. Markers of cerebellar white matter injury were elevated in ataxia-telangiectasia vs controls (apparent diffusion coefficient: 0.89×10−3mm2s−1 vs 0.69×10−3mm2s−1, p less than 0.0005) and correlated (age-corrected) with neurometabolite ratios indicating impaired neuronal viability (N-acetylaspartate:creatine r=-0.70, P less than 0.001); gliosis (inositol:creatine r=0.50, P=0.018; combined glutamine/glutamate:creatine r=-0.55, P=0.008) and increased myelin turnover (choline:creatine r=0.68, P less than 0.001). Fractional 4th ventricular volume was the only variable retained in the regression model predicting neurological function (adjusted r2=0.29, P=0.015).ConclusionsQuantitative MRI demonstrates cerebellar abnormalities in children with A-T, providing non-invasive measures of progressive cerebellar injury and markers reflecting neurological status. These MRI metrics may be of value in determining timing and impact of interventions aimed at altering the natural history of A-T