Ex-vivo perfusion bioassay : an excellent technique to measure the bioactivity of inhalable insulin coated microcrystals

Purpose: To measure the bioactivity of inhalable insulin coated microcrystals using a perfusion bioassay that measures its vasodilatory effect on smooth muscle arterial tissue. Methods: The bioactivity of an insulin protein coated microcrystal (PCMC), a potential candidate for pulmonary drug delivery and commercial insulin was determined on a Danish Myo Tech P110 pressure myograph system. 12 week old Mesenteric resistance arteries from Male Wistar rats were isolated and immersed in a physiological salt solution (PSS) and attached to 2 opposing hollow glass micro-cannula (outer diameter 80 microns). The PSS was gradually warmed to 37°C (at a pressure less than 5mm Hg) for 1hr. Subsequently the pressure was increased up to 40mm Hg over a period 15 minutes and equilibrated for a further 15 minutes after gassing with 95%O2 / 5%CO2 to achieve a pH of 7.4 at 37°C. After normalisation by two washes of 123mM KCl and exposure to 1-10mM noradrenaline the arteries were exposed intraluminally to each insulin preparation by gradual infusion directly into the lumen via a fetal microcannulae inserted to the tip of the glass mounting cannula, at a constant pressure. Results: The preliminary results (full cummulative response curve yet to be determined) demonstrate insulin mediated relaxation to noradrenaline preconstriction. The level of constriction drops from 100% to 42% as the concentration of insulin increases from -11 to -9 Log M for the PCMC compared with a drop from 100 % to 65% for the commercial insulin preparation. However the more potent vasodilatory effect found for the insulin PCMC is more likely to be a result of variance introduced in each dilution step than a real increase in potency. Conclusion: The perfusion bioassay technique provides an excellent method of measuring insulin bioactivity and indicates the insulin loaded on the microcrystal support is fully active

Understanding the Impact of INDOT Projects on Automotive Industry Cluster Logistics Costs: A Case Study of the Honda Plant

This study focuses on understanding the impact of INDOT projects on the Honda, Greensburg plant’s supply chain. The goal of the study was th

A scoping review to catalogue tinnitus problems in children

© 2019 The Authors Background: The reported prevalence of tinnitus in children is similar to that in adults. However, unlike adults, there is relatively little understanding of the tinnitus-related problems children experience. Knowledge of the problems experienced by adults has led to the development of numerous clinical questionnaires used by health professionals in assessment and treatment practices; to date no child-specific questionnaire measure of tinnitus has been developed. To support development of a questionnaire measure of tinnitus in children, the aim of this scoping review was to catalogue the peer-reviewed and grey scientific literature according to 1) the methods used to identify problems experienced by children with tinnitus, 2) tinnitus-related problems observed in or reported by children, and 3) research recommendations suggested by investigators with regards to tinnitus in children. Methods: A scoping review was conducted following an established methodological framework. Records were included where a tinnitus-related problem was reported in a child 18 years or younger, and tinnitus was reported as the primary complaint. Tinnitus problems were extracted and categorised into problem themes. Results: Thirty-five records met the inclusion criteria for this review. Methods used to identify tinnitus-related problems in children, and the number and range of problems reported, varied across the records. Symptom impact was summarised according to six problem themes; Physical health, Cognitive health, Hearing and listening, Emotional health, Quality of life, and Feeling different/isolated. Identified research recommendations highlighted a demand for more standardised approaches. Conclusions: The findings evidence the detrimental impact tinnitus can have on a child's quality of life and emotional wellbeing. The current British Society of Audiology Tinnitus in Children Practice Guidance recommends management practices to address the most broadly reported problems identified in this review; sleep difficulties, emotional difficulties, and concentration and hearing problems at school. Given the finding of this review, we suggest problems relating to the impact of tinnitus on quality of life and feelings of isolation are also important problem domains to consider when managing a child who has tinnitus. Current variability in the approach to identifying children's tinnitus problems underlines the importance of developing a standardised and dedicated measure of tinnitus in children

Development of the impact of tinnitus in children questionnaire (iTICQ)

Introduction: Tinnitus is a common disorder of the auditory system. Questionnaires are essential tools for clinical assessment and research. Whilst many questionnaires are available to measure different aspects of tinnitus complaint in adults, there is currently no self-report questionnaire measure of tinnitus that has been developed for or is suitable for use with children. This study describes the development of the first self-report measure of tinnitus impact for children aged 8–16 years old. Methods: Two phases of questionnaire development were conducted. In Phase 1 children's tinnitus-related problems were elicited from interviews with children with tinnitus (n = 11; aged 9–16 years old), parents (n = 5), and clinicians (n = 8). Interview transcripts were analyzed using qualitative content analysis. Findings were combined with problems identified by the clinical co-authors, researchers, and clinicians in a conference workshop, and those previously reported in service evaluation of UK National Health Service pediatric tinnitus services and in a scoping review. From this, a conceptual framework of tinnitus impact on health-related quality of life in children was developed. Based on the conceptual framework, a 38-item pilot questionnaire was drafted. In Phase 2, content validity of the pilot questionnaire was assessed in cognitive interviews with six children who had tinnitus (aged 8–15 years old) and an online survey with clinicians working in pediatric tinnitus services (n = 8 services and 28 clinicians). Finally, readability assessments were conducted. Feedback led to iterative revisions to the questionnaire. The final questionnaire was named the Impact of Tinnitus in Children Questionnaire (iTICQ). Results: The iTICQ contains three scene setting (non-scoring) items, and 33 scoring items covering six domains of tinnitus impact: Sleep and Feeling Tired, Learning, Emotional Health, Hearing and Listening, Taking Part, and Relationships. Conclusions: The iTICQ is a new self-report measure of tinnitus impact that can be self-completed by children aged 8–16 years old. It shows good content validity and can be used to measure problem severity across the domains of core relevance to children with tinnitus. Further validation studies and translations of the iTICQ are indicated to determine its psychometric properties in different child populations and to make it widely accessible