Automated computational analysis reveals structural changes in the enteric nervous system of nNOS deficient mice

Neuronal nitric oxide synthase (nNOS) neurons play a fundamental role in inhibitory neurotransmission, within the enteric nervous system (ENS), and in the establishment of gut motility patterns. Clinically, loss or disruption of nNOS neurons has been shown in a range of enteric neuropathies. However, the effects of nNOS loss on the composition and structure of the ENS remain poorly understood. The aim of this study was to assess the structural and transcriptional consequences of loss of nNOS neurons within the murine ENS. Expression analysis demonstrated compensatory transcriptional upregulation of pan neuronal and inhibitory neuronal subtype targets within the Nos1−/− colon, compared to control C57BL/6J mice. Conventional confocal imaging; combined with novel machine learning approaches, and automated computational analysis, revealed increased interconnectivity within the Nos1−/− ENS, compared to age-matched control mice, with increases in network density, neural projections and neuronal branching. These findings provide the first direct evidence of structural and molecular remodelling of the ENS, upon loss of nNOS signalling. Further, we demonstrate the utility of machine learning approaches, and automated computational image analysis, in revealing previously undetected; yet potentially clinically relevant, changes in ENS structure which could provide improved understanding of pathological mechanisms across a host of enteric neuropathies

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (ϰ = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (ϰ = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations

What happens after referral for sedation?

OBJECTIVE: To follow up 100 referrals to the sedation clinic examining dental anxiety and background of patients and assess how many patients attended for treatment planning, initial treatment, and completed treatment and describe their characteristics. Among those who attended for initial treatment, which type of sedation they received at initial treatment and what level of clinician they saw. DESIGN: Descriptive, cross sectional survey and review of case notes. SUBJECTS AND METHODS: Subjects were 100 consecutive new patients in Sedation and Special Care Guy’s and St Thomas NHS Foundation Trust. The notes were analysed by an experienced member of staff (CAB) and data entered into an Excel spreadsheet and an SPSS datafile created. These data were merged with a dataset containing their responses to the intake questionnaire and medical history for analysis. RESULTS: Of the 100 patients initially referred, 72 attended the treatment planning session, 66 of the 72 (92%) attended for initial dental treatment, and 33 of 66 (50%) completed treatment. Dental Fear Survey (DFS) scores were related to attendance at the initial treatment visit but not to completion of treatment. Patients with mental health problems encountered more barriers. Only 33 of 100 patients referred completed treatment. CONCLUSIONS: Attendance for treatment planning and initial treatment was high. Attendance is related to fear and mental health. Overall completion of treatment from referral was 33 percent