Shigella sonnei utilises colicins during inter-bacterial competition.

The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

The Use of Oral Midazolam to Facilitate the Ophthalmic Examination of Children with Autism and Developmental Disorders.

Ophthalmic examinations of developmentally delayed/autistic children are challenging. Oral midazolam may be a viable alternative to general anaesthesia for this indication. Single-centre retrospective cohort study (January 2018-March 2020). Oral midazolam (0.5 mg/kg, max 15 mg). Metrics included: patient demographics, examination completion rate, duration of stay and adverse events. 50 oral midazolam examinations were performed (45 patients). Mean age was 79.12 months. All had developmental delay (66.67% autism). Time to ophthalmic examination was 60.31 minutes. Eye examination was successfully completed in 98%. No adverse events were reported. Mean stay was 3.35 hours. Oral midazolam (0.5 mg/kg, max 15 mg) is associated with safe, successful completion of ophthalmic examinations in children previously unexaminable in clinic.

Novel COL4A2 variant in a large pedigree: Consequences and dilemmas.

Pathogenic COL4A2 variants cause abnormalities in collagen production and can have serious implications for a range of organ systems, most notably the brain. Herein, we describe a large family of first-degree relatives affected by a novel heterozygous variant in COL4A2 (c.3490G.A). A wide disease spectrum is described, from asymptomatic to symptomatic, including 2 children with porencephaly and co-existing juvenile idiopathic polyarthritis. During a subsequent pregnancy, antenatal testing identified a positive fetus. In view of the literature, we review management and genetic counselling dilemmas.

Prevalence of asthma in Galway school children 2004.

We aimed to ascertain the prevalence of asthma amongst Galway schoolchildren aged 9-10, and to compare the results to a similar study carried out in 1992. A questionnaire was distributed to parents of all children attending 4th class in Galway city schools. 652 of 750(87%) questionnaires were returned. Prevalence of "wheeze ever" was 27.6%, and "current wheeze" 16.3%. The prevalence of asthma was 18.5%. Of those with asthma there was a 2 to 1 male preponderance, 80% had mild asthma, 14% moderate, and 6% severe asthma. 80% were taking anti-asthma therapy, with 48% taking regular inhaled steroids. 84% had a diagnosis of asthma made by a doctor. Comparison with the study of 1992 shows little change in the prevalence of current wheeze, or asthma. There has however been a significant decline in the severity of asthma, and an increase in the use of prophylactic anti-asthma medication. Asthma prevalence appears to be stable in the age group studied. There is a much greater willingness to diagnose, and treat asthma in the community. The severity of asthma, as measured by attack frequency, has declined.

The prevalence of Down syndrome in County Galway.

This is a retrospective survey of all cases of Down syndrome recorded between 1981 and 2000 to mothers resident in Co. Galway. The study compares the incidence of Down syndrome in both decades and examines the effects of changing demographics on incidence rates. The overall prevalence rate was 26.8/10,000 live births for the full period. Although there were 5119 fewer births in the 1991-2000 period, the prevalence was 29.8/10,000 compared to 24.1/10,000 in the previous decade. Despite the falling birth rates and fertility rates observed in our study between the two decades we found that the higher prevalence of Down syndrome in the second decade was directly related to the significant increase in the proportion of women in the 30 plus age group. Our study also found the place of the child with Down syndrome in the family changed, with 25.3% being the 5th or more child in the first decade compared with 9.5% in the second decade.

A study looking at the effectiveness of developmental screening in identifying learning disabilities in early childhood.

This is a retrospective study of children under six years of age referred to the Brothers of Charity Early Intervention Services in County Galway, a service that caters for children under 6 years with learning disabilities. The aim in doing this study was to assess the value of routine developmental screening in identifying children with learning difficulties. This study also investigates the patterns and sources of referral to the remedial services provided by the Brothers of Charity and highlights possible avoidable delays in referral. The results showed that many children were referred for remedial services late. The reasons for late referral included late identification of some children with problems, insufficient co-ordination of community-based services and a lack of awareness of the importance of early intervention in some cases. As some communication disorders such as autism, autistic spectrum disorders and specific language delay may not express themselves until the later part of the second year of life, the 18-24 month developmental assessment is of vital importance. However identification of these disorders can present difficulties and may call for additional training for professionals involved in the developmental screening of children in that age group. The interval between initial identification and referral for remedial care in many cases was more than twelve months. We propose that, in order to minimize this time, children requiring a more in-depth assessment should be assessed by a community-based multidisciplinary team, enabling integrated assessment by the different disciplines and thus speedier referral to remedial services.

Intussusception associated with bacterial meningitis.

Despite its common association with viral illnesses, intussusception has only rarely been found in the presence of bacterial infections. Two infants are described, both of whom were admitted to hospital with bilious vomiting, drowsiness, and dehydration. Both infants required urgent intravenous volume expansion. Intussusception was confirmed, and reduction was achieved by enema in both cases. Recovery was slow, and one infant developed a seizure. Evidence of meningococcal meningitis was found in both, with septicaemia in one. Neurological outcome is normal to date, and there has been no recurrence of intussusception in either case.

Consciousness and the natural method.

'Consciousness' is a superordinate term for a heterogeneous array of mental state types. The types share the property of 'being experienced' or 'being experiences'--'of there being something that it is like for the subject to be in one of these states.' I propose that we can only build a theory of consciousness by deploying 'the natural method' of coordinating all relevant informational resources at once, especially phenomenology, cognitive science, neuroscience and evolutionary biology. I'll provide two examples of the natural method in action in mental domains where an adaptationist evolutionary account seems plausible: (i) visual awareness and (ii) conscious event memory. Then I will discuss a case, (iii), dreaming, where I think no adaptationist evolutionary account exists. Beyond whatever interest the particular cases have, the examination will show why I think that a theory of mind, and the role conscious mentation plays in it, will need to be built domain-by-domain with no a priori expectation that there will be a unified account of the causal role or evolutionary history of different domains and competences.