Evaluation of large volume yeast interfering RNA lure-and-kill ovitraps for attraction and control of Aedes mosquitoes.

Aedes mosquitoes (Diptera: Culicidae), principle vectors of several arboviruses, typically lay eggs in man-made water-filled containers located near human dwellings. Given the widespread emergence of insecticide resistance, stable and biofriendly alternatives for mosquito larviciding are needed. Laboratory studies have demonstrated that inactivated yeast interfering RNA tablets targeting key larval developmental genes can be used to facilitate effective larvicidal activity while also promoting selective gravid female oviposition behaviour. Here we examined the efficacy of transferring this technology toward development of lure-and-kill ovitraps targeting Aedes aegypti (L.) and Aedes albopictus (Skuse) female mosquitoes. Insectary, simulated field and semi-field experiments demonstrated that two mosquito-specific yeast interfering RNA pesticides induce high levels of mortality among larvae of both species in treated large volume containers. Small-scale field trials conducted in Trinidad, West Indies demonstrated that large volume ovitrap containers baited with inactivated yeast tablets lure significantly more gravid females than traps containing only water and were highly attractive to both A. aegypti and A. albopictus females. These studies indicate that development of biorational yeast interfering RNA-baited ovitraps may represent a new tool for control of Aedes mosquitoes, including deployment in existing lure-and-kill ovitrap technologies or traditional container larviciding programs.

Movement disorders after hypoxic brain injury following cardiac arrest in adults.

BACKGROUND AND PURPOSE: Post-hypoxic movement disorders and chronic post-hypoxic myoclonus are rare complications after cardiac arrest in adults. Our study investigates the clinical spectrum, neuroimaging results, therapy and prognosis of these debilitating post-hypoxic sequelae. METHODS: This retrospective study included 72 patients from the neurological intensive care unit at a university hospital, who were diagnosed with hypoxic-ischaemic encephalopathy after cardiac arrest between January 2007 and September 2018. Clinical records were screened for occurrence of post-hypoxic movement disorders and chronic post-hypoxic myoclonus. Affected patients were further analysed for applied neuroprognostic tests, administered therapy and treatment response, and the outcome of these movement disorders and neurological function. RESULTS: Nineteen out of 72 screened patients exhibited post-hypoxic motor symptoms. Basal ganglia injury was the most likely neuroanatomical correlate of movement disorders as indicated by T1 hyperintensities and hypometabolism of this region in magnetic resonance imaging and positron emission tomography computed tomography. Levomepromazine and intrathecal baclofen showed first promising and mostly prompt responses to control these post-hypoxic movement disorders and even hyperkinetic storms. In contrast, chronic post-hypoxic myoclonus best responded to co-application of clonazepam, levetiracetam and primidone. Remission rates of post-hypoxic movement disorders and chronic post-hypoxic myoclonus were 58% and 50%, respectively. Affected patients seemed to present a rather good recovery of cognitive functions in contrast to the often more severe physical deficits. CONCLUSIONS: Post-hypoxic movement disorders associated with pronounced basal ganglia dysfunction might be efficiently controlled by levomepromazine or intrathecal baclofen. Their occurrence might be an indicator for a more unfavourable, but often not devastating, neurological outcome.

Considerations for Mean Upper Cervical Cord Area Implementation in a Longitudinal MRI Setting: Methods, Interrater Reliability, and MRI Quality Control.

BACKGROUND AND PURPOSE: Spinal cord atrophy is commonly measured from cerebral MRIs, including the upper cervical cord. However, rescan intraparticipant measures have not been investigated in healthy cohorts. This study investigated technical and rescan variability in the mean upper cervical cord area calculated from T1-weighted cerebral MRIs. MATERIALS AND METHODS: In this retrospective study, 8 healthy participants were scanned and rescanned with non-distortion- and distortion-corrected MPRAGE sequences (11-50 sessions in 6-8 months), and 50 participants were scanned once with distortion-corrected MPRAGE sequences in the Day2day daily variability study. From another real-world observational cohort, we collected non-distortion-corrected MPRAGE scans from 27 healthy participants (annually for 2-4 years) and cross-sectionally from 77 participants. Statistical analyses included coefficient of variation, smallest real difference, intraclass correlation coefficient, Bland-Altman limits of agreement, and paired t tests. RESULTS: Distortion- versus non-distortion-corrected MPRAGE-derived mean upper cervical cord areas were similar; however, a paired t test showed incomparability (t = 11.0, P = <.001). Higher variability was found in the mean upper cervical cord areas calculated from an automatic segmentation method. Interrater analysis yielded incomparable measures in the same participant scans (t = 4.5, P = <.001). Non-distortion-corrected mean upper cervical cord area measures were shown to be robust in real-world data (t = -1.04, P = .31). The main sources of variability were found to be artifacts from movement, head/neck positioning, and/or metal implants. CONCLUSIONS: Technical variability in cord measures decreased using non-distortion-corrected MRIs, a semiautomatic segmentation approach, and 1 rater. Rescan variability was within ±4.4% for group mean upper cervical cord area when MR imaging quality criteria were met.

[Osteomalacia-Clinical aspects, diagnostics and treatment]. / Osteomalazie ­ Klinik, Diagnostik und Therapie.

Osteomalacia is a bone disease caused by impaired skeletal mineralization. Vitamin D dependent types have to be distinguished from hypophosphatemic forms. Typical signs and symptoms include diffuse bone pain, muscle weakness and fragility fractures. The fracture pattern in osteomalacia is typically different from that of osteoporosis. Fragility fractures of the pelvis, sacrum, distal parts of the foot, proximal tibia and ribs are indicators for osteomalacia, whereas femoral neck and vertebral fractures (wedged vertebra, fish vertebra, vertebra plana and cover plate impression fractures) are typical for osteoporosis. Unspecific clinical features may be the reason for a delayed diagnosis. The correct classification of the complaint is dependent on the knowledge of the pathophysiology of osteomalacia and performance of additional bone-specific examinations. Determination of specific laboratory parameters should follow a rational algorithm, supplemented by imaging methods and a bone biopsy.

Nociceptive activation in spinal cord and brain persists during deep general anaesthesia.

BACKGROUND: In clinical practice, analgesic drug doses applied during general anaesthesia are considered sufficient when clinical responses (e.g. movement, blood pressure and heart rate elevations) are suppressed during noxious stimulation. We investigated whether absent clinical responses are indicative of suppressed spinal and brain responsiveness to noxious stimulation in anaesthetised subjects. METHODS: Ten healthy volunteers were investigated during deep propofol anaesthesia supplemented with increasing doses of remifentanil in a stepwise manner. Noxious electrical stimuli at an intensity comparable with surgical stimulation were repeatedly administered at each targeted remifentanil concentration. During stimulation, we monitored both clinical responses (blood pressure, heart rate, and movement) and neuronal responses. Neuronal responses were assessed using functional magnetic resonance imaging, spinal reflex responses, and somatosensory evoked potentials. RESULTS: This monitoring combination was able to faithfully detect brain and spinal neuronal responses to the noxious stimulation. Although clinical responses were no longer detected at analgesic dosages similar to those used for general anaesthesia in clinical practice, spinal and brain neuronal responses were consistently observed. Opioid doses that are significantly larger than is usually used in clinical practice only reduced neuronal responses to 41% of their maximal response. CONCLUSIONS: Nociceptive activation persists during deep general anaesthesia despite abolished clinical responses. Absent clinical responses are therefore not indicative of absent nociception-specific activation. Thus, commonly accepted clinical responses might be inadequate surrogate markers to assess anti-nociception during general anaesthesia. Further research is required to investigate whether persistent nociception causes adverse effects on patient outcome.

MRI-Based Methods for Spinal Cord Atrophy Evaluation: A Comparison of Cervical Cord Cross-Sectional Area, Cervical Cord Volume, and Full Spinal Cord Volume in Patients with Aquaporin-4 Antibody Seropositive Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND PURPOSE: Measures for spinal cord atrophy have become increasingly important as imaging biomarkers in the assessment of neuroinflammatory diseases, especially in neuromyelitis optica spectrum disorders. The most commonly used method, mean upper cervical cord area, is relatively easy to measure and can be performed on brain MRIs that capture cervical myelon. Measures of spinal cord volume (eg, cervical cord volume or total cord volume) require longer scanning and more complex analysis but are potentially better suited as spinal cord atrophy measures. This study investigated spinal cord atrophy measures in a cohort of healthy subjects and patients with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders and evaluated the discriminatory performance of mean upper cervical cord cross-sectional area compared with cervical cord volume and total cord volume. MATERIALS AND METHODS: Mean upper cervical cord area, cervical cord volume, and total cord volume were measured using 3T MRIs from healthy subjects (n = 19) and patients with neuromyelitis optica spectrum disorders (n = 30). Group comparison and receiver operating characteristic analyses between healthy controls and patients with neuromyelitis optica spectrum disorders were performed. RESULTS: Mean upper cervical cord area, cervical cord volume, and total cord volume measures showed similar and highly significant group differences between healthy control subjects and patients with neuromyelitis optica spectrum disorders (P < .01 for all). All 3 measures showed similar receiver operating characteristic-area under the curve values (mean upper cervical cord area = 0.70, cervical cord volume = 0.75, total cord volume = 0.77) with no significant difference between them. No associations among mean upper cervical cord cross-sectional area, cervical cord volume, or total cord volume with disability measures were found. CONCLUSIONS: All 3 measures showed similar discriminatory power between healthy control and neuromyelitis optica spectrum disorders groups. Mean upper cervical cord area is easier to obtain compared with cervical cord volume and total cord volume and can be regarded as an efficient representative measure of spinal cord atrophy in the neuromyelitis optica spectrum disorders context.

Decoding diagnosis and lifetime consumption in alcohol dependence from grey-matter pattern information.

OBJECTIVE: We investigated the potential of computer-based models to decode diagnosis and lifetime consumption in alcohol dependence (AD) from grey-matter pattern information. As machine-learning approaches to psychiatric neuroimaging have recently come under scrutiny due to unclear generalization and the opacity of algorithms, our investigation aimed to address a number of methodological criticisms. METHOD: Participants were adult individuals diagnosed with AD (N = 119) and substance-naïve controls (N = 97) ages 20-65 who underwent structural MRI. Machine-learning models were applied to predict diagnosis and lifetime alcohol consumption. RESULTS: A classification scheme based on regional grey matter attained 74% diagnostic accuracy and predicted lifetime consumption with high accuracy (r = 0.56, P < 10-10 ). A key advantage of the classification scheme was its algorithmic transparency, revealing cingulate, insular and inferior frontal cortices as important brain areas underlying classification. Validation of the classification scheme on data of an independent trial was successful with nearly identical accuracy, addressing the concern of generalization. Finally, compared to a blinded radiologist, computer-based classification showed higher accuracy and sensitivity, reduced age and gender biases, but lower specificity. CONCLUSION: Computer-based models applied to whole-brain grey-matter predicted diagnosis and lifetime consumption in AD with good accuracy. Computer-based classification may be particularly suited as a screening tool with high sensitivity.

Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study.

OBJECTIVE: To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. METHODS: We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. RESULTS: DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. CONCLUSION: NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. KEY POINTS: • The hypothesis of a widespread brain damage in NMOSD is challenged. • The optic radiation (OR) is the most severely affected region. • OR-affection is likely due to secondary degeneration following optic neuritis. • DTI is currently the most sensitive technique for NMOSD-related brain-damage detection. • DTI is currently the most reliable technique for NMOSD-related brain-damage detection.

Reduced Myelin Water in the White Matter Tracts of Patients with Niemann-Pick Disease Type C.

Previous studies using diffusion tensor imaging to examine white matter in Niemann-Pick disease type C have produced mixed results. However, diffusion tensor imaging does not directly measure myelin and may be affected by other structural changes. We used myelin water imaging to more directly examine demyelination in 2 patients with Niemann-Pick disease type C. The results suggest that this technique may be useful for identifying regional changes in myelination in this condition.

Altered basal ganglia functional connectivity in multiple sclerosis patients with fatigue.

BACKGROUND: Fatigue is one of the most frequent and disabling symptoms in multiple sclerosis, but its pathophysiological mechanisms are poorly understood. It is in particular unclear whether and how fatigue relates to structural and functional brain changes. OBJECTIVE: We aimed to analyse the association of fatigue severity with basal ganglia functional connectivity, basal ganglia volumes, white matter integrity and grey matter density. METHODS: In 44 patients with relapsing-remitting multiple sclerosis and 20 age- and gender-matched healthy controls, resting-state fMRI, diffusion tensor imaging and voxel-based morphometry was performed. RESULTS: In comparison with healthy controls, patients showed alteration of grey matter density, white matter integrity, basal ganglia volumes and basal ganglia functional connectivity. No association of fatigue severity with grey matter density, white matter integrity and basal ganglia volumes was observed within patients. In contrast, fatigue severity was negatively correlated with functional connectivity of basal ganglia nuclei with medial prefrontal cortex, precuneus and posterior cingulate cortex in patients. Furthermore, fatigue severity was positively correlated with functional connectivity between caudate nucleus and motor cortex. CONCLUSION: Fatigue is associated with distinct alterations of basal ganglia functional connectivity independent of overall disability. The pattern of connectivity changes suggests that disruption of motor and non-motor basal ganglia functions, including motivation and reward processing, contributes to fatigue pathophysiology in multiple sclerosis.

Outcome prediction in patients after cardiac arrest: a simplified method for determination of gray-white matter ratio in cranial computed tomography.

PURPOSE: Out-of-hospital cardiac arrest is a frequent cause of death in Europe. Hypoxic ischemic encephalopathy (HIE) often develops in initial survivors, and the question of treatment limitation arises in severely affected patients. To establish a poor prognosis with a high level of certainty, the use of a combination of prognostic parameters such as neurological examination, somatosensory evoked potentials, and neuron-specific enolase is common practice. A few recent studies suggest that gray-white matter ratio (GWR) determined from cranial computed tomography (CT) scans is an additional reliable predictor of poor prognosis. The standard GWR determination method involves measurements of 16 different regions of interest (ROIs). We tested whether a simplified method to obtain GWR has equivalent reliability for poor outcome prediction. MATERIALS AND METHODS: We retrospectively analyzed 98 patients after cardiac arrest who had been treated with hypothermia. CT scans were obtained within the first 7 days after cardiac arrest. Neurological outcome was determined at intensive care unit discharge. Four different methods to obtain GWR were compared in a receiver-operating characteristic curve analysis with respect to their prognostic value for poor outcome prediction. RESULTS: The simplest method using only four ROIs (putamen and internal capsule bilaterally) had the same prognostic value compared with the standard method using 16 ROIs. The simplified GWR predicted poor outcome with a sensitivity of 44 % at 100 % specificity. CONCLUSION: Our results indicate that for poor outcome prediction in survivors of cardiac arrest, a simplified GWR determination is feasible and has the same reliability as the complex standard procedure.

Exploiting coherence for real-time studies by single-bunch imaging.

First real-time studies of ultra-fast processes by single-bunch imaging at the European Synchrotron Radiation Facility are reported. By operating the storage ring of the ESRF in single-bunch mode with its correspondingly increased electron bunch charge density per singlet, the polychromatic photon flux density at insertion-device beamlines is sufficient to capture hard X-ray images exploiting the light from a single bunch (the corresponding bunch length is 140 ps FWHM). Hard X-ray imaging with absorption contrast as well as phase contrast in combination with large propagation distances is demonstrated using spatial samplings of 11 µm and 35 µm pixel size. The images acquired allow one to track crack propagation in a bursting piece of glass, breaking of an electrical fuse as well as cell wall rupture in an aqueous foam. Future developments and their potential in the frame of the proposed Phase II of the ESRF Upgrade Program are discussed.

Diffusion tensor imaging in amyotrophic lateral sclerosis--increased sensitivity with optimized region-of-interest delineation.

PURPOSE: Diagnosis of amyotrophic lateral sclerosis (ALS) can be difficult from clinical symptoms alone. Diffusion tensor imaging (DTI) has been suggested as an adjunct diagnostic method. DTI parameter changes have been repeatedly demonstrated, especially in the corticospinal tract (CST) as the predominantly affected structure. However, a recent meta-analysis reported only a modest discriminatory capability, questioning the value of this method as a confirmatory test in single subjects with suspected ALS. We investigated how methodological differences in CST delineation influence the discriminatory capability. METHODS: DTI data were acquired in 13 ALS patients and an age-matched healthy control group. We calculated and compared receiver operation characteristic (ROC) curves of four different analysis methods using either a manual or an atlas-based region of interest (ROI) of the CST in combination with and without tract-based spatial statistics (TBSS). RESULTS: The analysis method combining atlas-based ROIs with TBSS yielded an area under the curve (AUC) of 0.936 and a sensitivity and specificity of 100 % and 91.67 %. These are the best results among the four analysis methods evaluated: manual ROIs (AUC = 0.846, sensitivity: 69.23, specificity: 91.67), atlas-based ROIs alone (AUC = 0.917, sensitivity: 76.92, specificity: 91.67), manual ROIs in combination with TBSS (AUC = 0.885, sensitivity: 76.92, specificity: 91.67). CONCLUSIONS: Sensitivity and specificity strongly depend on the CST delineation approach. The combination of an atlas-based ROI with TBSS is a promising fully automatic method with improved discriminatory capability compared to other approaches. It could ultimately serve as a confirmatory test in single ALS patients.

Time dependency of bone density estimation from computed tomography with intravenous contrast agent administration.

UNLABELLED: Our study has demonstrated that in contrast-enhanced multi-detector computed tomography (MDCT)-based bone density measurements, the scan delay time after contrast agent administration is a statistically significant variable for the derivation of quantitative computed tomography (QCT)-equivalent bone mineral density (BMD) values. INTRODUCTION: Earlier investigators have proposed to derive QCT-equivalent BMD values from contrast-enhanced MDCT scans by using a merely density-based conversion equation. The purpose of this study was to investigate whether the scan delay after intravenous (IV) contrast agent administration might affect BMD values derived in this way. METHODS: A retrospective data analysis was performed on 198 subjects who underwent standardized biphasic MDCT. Average densities values (in Hounsfield units) of lumbar vertebral bodies 1 to 3 (L1-L3) were compared between phases I and II of the biphasic MDCT scan. Furthermore, QCT-equivalent BMD (BMDQCT) values were calculated using a previously published conversion equation. RESULTS: Paired t-test analysis revealed that IV contrast agent administration leads to a statistically significant increase (8.6 %; p < 0.0001) in overall density of L1-L3 from phases I to II. Moreover, comparison of BMDQCT values between phases I and II reveals a change from osteoporotic to osteopenic in 4.5 % of the study population and from osteopenic to normal for 11.1 % of the subjects. Furthermore, it was revealed that the density increase from phases I to II shows a weak, yet statistically significant (p < 0.001) age dependency. CONCLUSIONS: Our study demonstrates that the use of a mere density-based conversion equation for deriving BMDQCT from MDCT scans ignores time dependency as an important variable. Furthermore, our results indicate that the actual age-dependent BMD itself might be another relevant variable that needs to be included in a MDCT-to-QCT conversion equation.

Diffusion tensor imaging of skeletal muscle--correlation of fractional anisotropy to muscle power.

PURPOSE: Recent DTI studies demonstrated the possibility of fiber geometry visualization in skeletal muscle. We tested for an association between muscle power and standard DTI parameters, e. g. fractional anisotropy. MATERIALS AND METHODS: Maximal muscle power (Lmax) of the soleus muscle was determined in 11 healthy subjects. Subsequently DTI was performed and standard parameters (fractional anisotropy - FA, mean diffusivity - MD, parallel diffusivity - PD, radial diffusivity - RD) were extracted in an ROI of the soleus muscle. RESULTS: We found a signficant association of Lmax with FA (neg. correlation: r = -0.85, p = 0.0015) and RD (pos. correlation r = 0.80, p = 0.047). There was no signficant association of MD or PD. CONCLUSION: Maximum muscle power is an indirect measure of fiber type distribution. The correlation between muscle power and DTI parameters can be explained by differences in fiber diameter and differences in the intracellular microstructure of type-1 and type-2 fibers. DTI should be evaluated as a tool for non-invasive quantification of fiber type distribution in skeletal muscle.

Myelination deficits in schizophrenia: evidence from diffusion tensor imaging.

BACKGROUND: Diffusion Tensor Imaging studies have repeatedly shown a decrease of the fractional anisotropy (FA) parameter in patients with schizophrenia. This has been interpreted as a disturbed microstructural integrity of white matter. However, FA is a relative parameter that is derived from eigenvalues of the diffusion tensor and FA reductions may be the result of decreases in parallel diffusivity (PD) or increases in radial diffusivity (RD). Despite the well-established FA reduction in schizophrenia, little is known what this reduction is based on. METHODS: Seventeen patients with schizophrenia were scanned with a DTI protocol and compared to a group of healthy control subjects. In addition to an FA comparison, a detailed analysis of PD and RD values was performed with two approaches to localize changes in diffusion values, i.e. a voxel-based analysis and an anatomically based tract specific analysis. RESULTS: We found significantly decreased FA values in the patient group when compared to healthy controls. FA decreases were based on an increase in RD, while we observed no significant changes of PD. These changes were predominantly localized in frontal and temporal areas. CONCLUSION: RD increases as the underlying change in FA decreases is suggestive of desintegration of myelin, which is in line with histopathological studies suggesting a disturbed myelination in schizophrenia.

The state and fate of Himalayan glaciers.

Himalayan glaciers are a focus of public and scientific debate. Prevailing uncertainties are of major concern because some projections of their future have serious implications for water resources. Most Himalayan glaciers are losing mass at rates similar to glaciers elsewhere, except for emerging indications of stability or mass gain in the Karakoram. A poor understanding of the processes affecting them, combined with the diversity of climatic conditions and the extremes of topographical relief within the region, makes projections speculative. Nevertheless, it is unlikely that dramatic changes in total runoff will occur soon, although continuing shrinkage outside the Karakoram will increase the seasonality of runoff, affect irrigation and hydropower, and alter hazards.

Magnetic resonance imaging in transient global amnesia: lessons learned from 198 cases.

PURPOSE: Patients with transient global amnesia (TGA) present with a characteristic clinical syndrome although other differential diagnoses have to be considered. Diffusion-weighted imaging (DWI) represents a highly specific diagnostic tool in the context of TGA; however, standard clinical DWI often fails to detect the small characteristic hippocampal lesions. The diagnostic success of DWI sequences in TGA patients was analyzed with respect to slice thickness and time interval between symptom onset. METHODS: Magnetic resonance imaging (MRI) studies of 198 patients with clinically diagnosed TGA were retrospectively analyzed. All DWI studies were grouped according to the slice thickness applied (3 mm, 5 mm and 6 mm). The three groups were assessed for group-specific detection rates of hippocampal lesions with diffusion restriction. In addition the detection rates were evaluated with respect to the time interval between TGA symptom onset and MRI examination. RESULTS: A significant increase in detection rates (about 8.4% per mm) was found when thinner slices were acquired (44.7% for 3 mm, 27.1% for 5 mm and 19.6% for 6 mm slice thickness). The detection rate was highest (up to 80%) when MRI was performed 2 days after TGA symptom onset. CONCLUSIONS: The MRI protocol in patients with TGA should include a DWI sequence with a slice thickness of 3 mm or less. The examination should be performed on day 2 after symptom onset to fully exploit the diagnostic value of DWI which represents a sensitive and specific diagnostic tool for patients with TGA.