High dose, fast delivery magnesium sulphate in a 3-year-old acute severe asthmatic

Acute severe asthma when respiratory failure is imminent is not addressed in world asthma guidelines. Intravenous magnesium sulphate, salbutamol and aminophylline all have advocates but what order, speed of delivery or dosage is left up to the individual physician treating the patient. A child in respiratory failure was given a large, fast dose of intravenous magnesium sulphate before intravenous salbutamol which relaxed bronchial smooth muscle immediately and tracheal intubation and lung ventilation was avoided. Justification for this treatment is discussed

Pseudotumor cerebri syndrome in childhood : incidence, clinical profile and risk factors in a national prospective population-based cohort study

Aim To investigate the epidemiology, clinical profile and risk factors of pseudotumor cerebri syndrome (PTCS) in children aged 1-16 years. Methods A national prospective population-based cohort study over 25 months. Newly diagnosed PTCS cases notified via British Paediatric Surveillance Unit (BPSU) were ascertained using classical diagnostic criteria and categorised according to 2013 revised diagnostic criteria. We derived national age, sex and weight-specific annual incidence rates and assessed effects of sex and weight category. Results We identified 185 PTCS cases of which 166 also fulfilled revised diagnostic criteria. The national annual incidence (95% CI) of childhood PTCS aged 1-16 years was 0.71 (0.57- 0.87) per 100,000 population increasing with age and weight to 4.18 and 10.7 per 100,000 in obese 12-15 year old boys and girls respectively. Incidence rates under 7 years were similar in both sexes. From 7 years onwards, the incidence in girls was double that in boys, but only in overweight (including obese) children. In 12-15 year old children, an estimated 82% of the incidence of PTCS was attributable to obesity. Two subgroups of PTCS were apparent: 168 (91%) cases aged from 7 years frequently presented on medication and with headache, and were predominantly female and obese. The remaining 17 (9%) cases under 7 years often lacked these risk factors and commonly presented with new onset squint. Conclusions This uniquely largest population-based study of childhood PTCS will inform the design of future intervention studies. It suggests that weight reduction is central to the prevention of PTCS

Potential for Increased Human Foodborne Exposure to PCDD/F When Recycling Sewage Sludge on Agricultural Land

Sewage sludge from municipal wastewater treatment is used in agriculture as a nutrient source and to aid in moisture retention. To examine the potential impact of sludge-amended soil on exposures to polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from plant and animal foods, we conducted a review of published empirical data from international sources. Levels of PCDD/F in municipal sewage sludge ranged from 0.0005 to 8,300 pg toxic equivalents (TEQ)/g. Background levels in soil ranged from 0.003 to 186 pg TEQ/g. In sludge-amended soils, levels of PCDD/F ranged from 1.4 to 15 pg TEQ/g. Studies that measured levels before and after sludge treatment showed an increase in soil concentration after treatment. Relationships between PCDD/F levels in soil and resulting concentrations in plants were very weakly positive for unpeeled root crops, leafy vegetables, tree fruits, hay, and herbs. Somewhat stronger relationships were observed for plants of the cucumber family. In all cases, large increases in soil concentration were required to achieve a measurable increase in plant contamination. A considerably stronger positive relationship was observed between PCDD/F in feed and resulting levels in cattle tissue, suggesting bioaccumulation. Although PCDD/Fs are excreted in milk, no association was found between feed contamination and levels of PCDD/Fs measured in milk. There is a paucity of realistic data describing the potential for entry of PCDD/Fs into the food supply via sewage sludge. Currently available data suggest that sewage sludge application to land used for most crops would not increase human exposure. However, the use of sludge on land used to graze animals appears likely to result in increased human exposure to PCDD/F

Conscientious, competent and caring: producing the junior doctor of the future

This article is based on the Association for the Study of Medical Education Gold Medal Plenary for 2022, given by the first author. It outlines different ways in which medical training can be approached, based on his career and his work with colleagues. Among the attributes that it would be desirable to promote in future doctors are conscientiousness, competence and care for patients as individuals. This article explores each of these in separate sections. The first demonstrates that the trait of conscientiousness can be observed in first and second year medical students by their compliance in routine low level tasks such as attendance and submission of required work on time. A ‘conscientiousness index’ calculated on this basis is a statistically significant predictor of later events such as performance in exams, the prescribing safety assessment, and the UK situational judgement test in subsequent years, and also in postgraduate assessments such as Royal college exams and the annual reviews of competence progression. The second proposes that competence in tasks undertaken by junior doctors is better achieved by teaching on medical imaging, clinical skills and living anatomy than by cadaveric dissection. The final section argues that the incorporation of arts and humanities teaching into medical education is likely to lead to better understanding of the patient perspective in later practice

Precision cut lung slices: a novel versatile tool to examine host-pathogen interaction in the chicken lung

The avian respiratory tract is a common entry route for many pathogens and an important delivery route for vaccination in the poultry industry. Immune responses in the avian lung have mostly been studied in vivo due to the lack of robust, relevant in vitro and ex vivo models mimicking the microenvironment. Precision-cut lung slices (PCLS) have the major advantages of maintaining the 3-dimensional architecture of the lung and includes heterogeneous cell populations. PCLS have been obtained from a number of mammalian species and from chicken embryos. However, as the embryonic lung is physiologically undifferentiated and immunologically immature, it is less suitable to examine complex host-pathogen interactions including antimicrobial responses. Here we prepared PCLS from immunologically mature chicken lungs, tested different culture conditions, and found that serum supplementation has a detrimental effect on the quality of PCLS. Viable cells in PCLS remained present for ≥ 40 days, as determined by viability assays and sustained motility of fluorescent mononuclear phagocytic cells. The PCLS were responsive to lipopolysaccharide stimulation, which induced the release of nitric oxide, IL-1β, type I interferons and IL-10. Mononuclear phagocytes within the tissue maintained phagocytic activity, with live cell imaging capturing interactions with latex beads and an avian pathogenic Escherichia coli strain. Finally, the PCLS were also shown to be permissive to infection with low pathogenic avian influenza viruses. Taken together, immunologically mature chicken PCLS provide a suitable model to simulate live organ responsiveness and cell dynamics, which can be readily exploited to examine host-pathogen interactions and inflammatory responses

A public panel reviews applications and questions applicants: Team member and public contributor discuss a transparent and inclusive approach to data access reviews

Objectives We created a panel with members of the public and longitudinal study participants who review our data access requests. This panel forms an integral part of our data access application process, giving the public a say who can access the data for research. Methods We advertised our lay member vacancies using social media, newsletters, word of mouth and the internet. We appointed six people to the public panel. Our panel includes study participants, NHS service users, parents, carers, and people with experience of disability, neurodiversity, and long-term health conditions. The Panel Terms of Reference were created with help from stakeholders and study teams involved in longitudinal studies that involve the public in data access applications. This ensured that the purpose of the panel was clear. The panel reviews lay summaries and makes sure that researchers have adequate public involvement in their project. Results Panel members have reviewed 28 applications. Researchers present their research at an online meeting with the panel then answer questions from the panel members. We publish meeting minutes on our website for transparency. A 6-month review was overwhelmingly positive - all panel members indicated they felt valued. They felt able to challenge and question researchers as part of the data access application process. This provides a level of public scrutiny to our work. “I feel there’s a real value in the panel. You get a real sense that this has got such potential to make a contribution.” (panel member) We are further developing the Panel Terms of Reference with panel members. We will consider additional areas of responsibility, for example, public benefit review. Conclusion We regularly review how to improve public involvement in our work. The panel has proven its value during our application process. Therefore we are exploring with the panel a new approach to assess the public benefit of applications and what is meant by ‘public benefit research’

Integrin-Blocking Antibodies Delay Keratinocyte Re-Epithelialization in a Human Three-Dimensional Wound Healing Model

The α6β4 integrin plays a significant role in tumor growth, angiogenesis and metastasis through modulation of growth factor signaling, and is a potentially important therapeutic target. However, α6β4-mediated cell-matrix adhesion is critical in normal keratinocyte attachment, signaling and anchorage to the basement membrane through its interaction with laminin-5, raising potential risks for targeted therapy. Bioengineered Human Skin Equivalent (HSE), which have been shown to mimic their normal and wounded counterparts, have been used here to investigate the consequences of targeting β4 to establish toxic effects on normal tissue homeostasis and epithelial wound repair. We tested two antibodies directed to different β4 epitopes, one adhesion-blocking (ASC-8) and one non-adhesion blocking (ASC-3), and determined that these antibodies were appropriately localized to the basal surface of keratinocytes at the basement membrane interface where β4 is expressed. While normal tissue architecture was not altered, ASC-8 induced a sub-basal split at the basement membrane in non-wounded tissue. In addition, wound closure was significantly inhibited by ASC-8, but not by ASC-3, as the epithelial tongue only covered 40 percent of the wound area at 120 hours post-wounding. These results demonstrate β4 adhesion-blocking antibodies may have adverse effects on normal tissue, whereas antibodies directed to other epitopes may provide safer alternatives for therapy. Taken together, we conclude that these three-dimensional tissue models provide a biologically relevant platform to identify toxic effects induced by candidate therapeutics, which will allow generation of findings that are more predictive of in vivo responses early in the drug development process

Shaping public opinion on the issue of childbirth; a critical analysis of articles published in an Australian newspaper

<p>Abstract</p> <p>Background</p> <p>The Australian government has announced a major program of reform with the move to primary maternity care, a program of change that appears to be at odds with current general public perceptions regarding how maternity care is delivered.</p> <p>Methods</p> <p>A critical discourse analysis of articles published in 'The Age', a newspaper with national distribution, subsequent to the release of the discussion paper by the Australian Government in 2008 was undertaken. The purpose was to identify how Australian maternity services are portrayed and what purpose is served by this representation to the general public.</p> <p>Results</p> <p>Findings from this critical discourse analysis revealed that Australian maternity services are being portrayed to the general public as an inflexible outdated service struggling to meets the needs of pregnant women and in desperate need of reform. The style of reporting employed in this newspaper involved presenting to the reader the range of expert opinion relevant to each topic, frequently involving polarised positions of the experts on the issue.</p> <p>Conclusions</p> <p>The general public are presented with a conflict, caught between the need for changes that come with the primary maternity model of care and fear that these change will undermine safe standards. The discourse; 'Australia is one of the safest countries in which to give birth or be born, what is must be best', represents the situation where despite major deficiencies in the system the general public may be too fearful of the consequences to consider a move away from reliance on traditional medical-led maternity care.</p