Foreground Detection Analysis of Ultrasound Image Sequences Identifies Markers of Motor Neurone Disease across Diagnostically Relevant Skeletal Muscles

© 2019 The Authors Diagnosis of motor neurone disease (MND) includes detection of small, involuntary muscle excitations, termed fasciculations. There is need to improve diagnosis and monitoring of MND through provision of objective markers of change. Fasciculations are visible in ultrasound image sequences. However, few approaches that objectively measure their occurrence have been proposed; their performance has been evaluated in only a few muscles; and their agreement with the clinical gold standard for fasciculation detection, intramuscular electromyography, has not been tested. We present a new application of adaptive foreground detection using a Gaussian mixture model (GMM), evaluating its accuracy across five skeletal muscles in healthy and MND-affected participants. The GMM provided good to excellent accuracy with the electromyography ground truth (80.17%–92.01%) and was robust to different ultrasound probe orientations. The GMM provides objective measurement of fasciculations in each of the body segments necessary for MND diagnosis and hence could provide a new, clinically relevant disease marker

Validation of a New Semi-Automated Technique to Evaluate Muscle Capillarization.

The method of capillary domains has often been used to study capillarization of skeletal and heart muscle. However, the conventional data processing method using a digitizing tablet is an arduous and time-consuming task. Here we compare a new semi-automated capillary domain data collection and analysis in muscle tissue with the standard capillary domain method. The capillary density (1481 ± 59 vs. 1447 ± 54 caps mm(-2); R(2):0.99; P < 0.01) and heterogeneity of capillary spacing (0.085 ± 0.002 vs. 0.085 ± 0.002; R(2):0.95; P < 0.01) were similar in both methods. The fiber cross-sectional area correlated well between the methods (R(2):0.84; P < 0.01) and did not differ significantly (~8 % larger in the old than new method at P = 0.08). The latter was likely due to differences in outlining the contours between the two methods. In conclusion, the semi-automated method gives quantitatively and qualitatively similar data as the conventional method and saves a considerable amount of time

Ultrasound-Based Detection of Fasciculations in Healthy and Diseased Muscles

Involuntary muscle activations are diagnostic indicators of neurodegenerative pathologies. Currently detected by invasive intramuscular electromyography, these muscle twitches are found to be visible in ultrasound images. We present an automated computational approach for the detection of muscle twitches, and apply this to two muscles in healthy and motor neuron disease-affected populations. The technique relies on motion tracking within ultrasound sequences, extracting local movement information from muscle. A statistical analysis is applied to classify the movement, either as noise or as more coherent movement indicative of a muscle twitch. The technique is compared to operator identified twitches, which are also assessed to ensure operator agreement. We find that, when two independent operators manually identified twitches, higher interoperator agreement (Cohen's k) occurs when more twitches are present (k = 0.94), compared to a lower number (k = 0.49). Finally, we demonstrate, via analysis of receiver operating characteristics, that our computational technique detects muscle twitches across the entire dataset with a high degree of accuracy (0.83 <; accuracy <; 0.96)

The utility of brain biopsy in pediatric cryptogenic neurological disease

OBJECTIVE: The authors’ aim was to characterize a single-center experience of brain biopsy in pediatric cryptogenic neurological disease. METHODS: The authors performed a retrospective review of consecutive brain biopsies at a tertiary pediatric neurosciences unit between 1997 and 2017. Children < 18 years undergoing biopsy for neurological pathology were included. Those with presumed neoplasms and biopsy performed in the context of epilepsy surgery were excluded. RESULTS: Forty-nine biopsies in 47 patients (25 females, mean age ± SD 9.0 ± 5.3 years) were performed during the study period. The most common presenting symptoms were focal neurological deficit (28.6%) and focal seizure (26.5%). Histopathological, microbiological, and genetic analyses of biopsy material were contributory to the diagnosis in 34 cases (69.4%). Children presenting with focal seizures or with diffuse (> 3 lesions) brain involvement on MRI were more likely to yield a diagnosis at biopsy (OR 3.07 and 2.4, respectively). Twelve patients were immunocompromised and were more likely to yield a diagnosis at biopsy (OR 6.7). Surgery was accompanied by severe complications in 1 patient. The most common final diagnoses were infective (16/49, 32.7%), followed by chronic inflammatory processes (10/49, 20.4%) and occult neoplastic disease (9/49, 18.4%). In 38 cases (77.6%), biopsy was considered to have altered clinical management. CONCLUSIONS: Brain biopsy for cryptogenic neurological disease in children was contributory to the diagnosis in 69.4% of cases and changed clinical management in 77.6%. Biopsy most commonly revealed underlying infective processes, chronic inflammatory changes, or occult neoplastic disease. Although generally safe, the risk of severe complications may be higher in immunocompromised and myelosuppressed children

Assessing sedimentation equilibrium profiles in analytical ultracentrifugation experiments on macromolecules: from simple average molecular weight analysis to molecular weight distribution and interaction analysis

Molecular weights (molar masses), molecular weight distributions, dissociation constants and other interaction parameters are fundamental characteristics of proteins, nucleic acids, polysaccharides and glycoconjugates in solution. Sedimentation equilibrium in the analytical ultracentrifugation provides a powerful method with no supplementary immobilization, columns or membranes required. It is particularly powerful when used in conjunction with its sister technique, namely sedimentation velocity analysis. We describe key approaches now available and their application to the characterisation of antibodies polysaccharides and glycoconjugates. We indicate how major complications such as thermodynamic non-ideality can now be routinely dealt with, thanks to a great extent to the extensive contribution of Professor DonWinzor over several decades of research

Cross-Sectional Surveys of the Prevalence of Follicular Trachoma and Trichiasis in The Gambia: Has Elimination Been Reached?

BACKGROUND: The Gambia's National Eye Health Programme has made a concerted effort to reduce the prevalence of trachoma. The present study had two objectives. The first was to conduct surveillance following mass drug administrations to determine whether The Gambia has reached the World Health Organization's (WHO) criteria for trachoma elimination, namely a prevalence of trachomatous inflammation-follicular (TF) of less than 5% in children aged 1 to 9 years. The second was to determine the prevalence of trichiasis (TT) cases unknown to the programme and evaluate whether these meet the WHO criteria of less than 0.1% in the total population. METHODOLOGY/PRINCIPAL FINDINGS: Three cross-sectional surveys were conducted between 2011 and 2013 to determine the prevalence of TF and TT in each of nine surveillance zones. Each zone was of similar size, with a population of 60,000 to 90,000, once urban settlements were excluded. Trachoma grading was carried out according to the WHO's simplified trachoma grading system. The prevalence of TF in children aged 1 to 9 years was less than 5% in each surveillance zone at each of the three surveys. The prevalence of TT cases varied by zone from 0 to 1.7% of adults greater than 14 years while the prevalence of TT cases unknown to the country's National Eye Health Programme was estimated at 0.15% total population. CONCLUSIONS/SIGNIFICANCE: The Gambia has reached the elimination threshold for TF in children. Further work is needed to bring the number of unknown TT cases below the elimination threshold

Population-based prevalence survey of follicular trachoma and trachomatous trichiasis in the Casamance region of Senegal.

BACKGROUND: Trachoma, caused by ocular infection with Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. We conducted the first population-based trachoma prevalence survey in the Casamance region of Senegal to enable the Senegalese National Eye Care Programme (NECP) to plan its trachoma control activities. The World Health Organization (WHO) guidelines state that any individual with trachomatous trichiasis (TT) should be offered surgery, but that surgery should be prioritised where the prevalence is >0.1%, and that districts and communities with a trachomatous inflammation, follicular (TF) prevalence of ≥10% in 1-9 year-olds should receive mass antibiotic treatment annually for a minimum of three years, along with hygiene promotion and environmental improvement, before re-assessing the prevalence to determine whether treatment can be discontinued (when TF prevalence in 1-9 year-olds falls 1% in all districts. CONCLUSION: With a prevalence <5%, TF does not appear to be a significant public health problem in this region. However, TF monitoring and surveillance at sub-district level will be required to ensure that elimination targets are sustained and that TF does not re-emerge as a public health problem. TT surgery remains the priority for trachoma elimination efforts in the region, with an estimated 1819 TT surgeries to conduct

Age- and Sex-Specific Mortality Patterns in an Emerging Wildlife Epidemic: The Phocine Distemper in European Harbour Seals

Analyses of the dynamics of diseases in wild populations typically assume all individuals to be identical. However, profound effects on the long-term impact on the host population can be expected if the disease has age and sex dependent dynamics. The Phocine Distemper Virus (PDV) caused two mass mortalities in European harbour seals in 1988 and in 2002. We show the mortality patterns were highly age specific on both occasions, where young of the year and adult (>4 yrs) animals suffered extremely high mortality, and sub-adult seals (1–3 yrs) of both sexes experienced low mortality. Consequently, genetic differences cannot have played a main role explaining why some seals survived and some did not in the study region, since parents had higher mortality levels than their progeny. Furthermore, there was a conspicuous absence of animals older than 14 years among the victims in 2002, which strongly indicates that the survivors from the previous disease outbreak in 1988 had acquired and maintained immunity to PDV. These specific mortality patterns imply that contact rates and susceptibility to the disease are strongly age and sex dependent variables, underlining the need for structured epidemic models for wildlife diseases. Detailed data can thus provide crucial information about a number of vital parameters such as functional herd immunity. One of many future challenges in understanding the epidemiology of the PDV and other wildlife diseases is to reveal how immune system responses differ among animals in different stages during their life cycle. The influence of such underlying mechanisms may also explain the limited evidence for abrupt disease thresholds in wild populations

Regulation of G protein-coupled receptors by palmitoylation and cholesterol

Due to their membrane location, G protein-coupled receptors (GPCRs) are subject to regulation by soluble and integral membrane proteins as well as membrane components, including lipids and sterols. GPCRs also undergo a variety of post-translational modifications, including palmitoylation. A recent article by Zheng et al. in BMC Cell Biology demonstrates cooperative roles for receptor palmitoylation and cholesterol binding in GPCR dimerization and G protein coupling, underlining the complex regulation of these receptors