Low serum myeloperoxidase in autistic children with gastrointestinal disease

Anthony J Russo1, Arthur Krigsman2, Bryan Jepson2, Andy Wakefield21Research Director, Health Research Institute/Pfeiffer Treatment Center, Warrenville, IL, USA; 2Thoughtful House Center for Children, Austin, TX, USAAim: To assess serum myeloperoxidase (MPO) levels in autistic children with severe gastrointestinal (GI) disease and to test the hypothesis that there is an association between serum MPO concentration and inflammatory GI disease, including antineutrophil cytoplasmic antibodies (ANCA), previously seen in a subgroup of autistic children.Subjects and methods: Serum from 40 autistic children with chronic digestive disease (most with ileo-colonic lymphoid nodular hyperplasia (LNH) and inflammation of the colorectum, small bowel and/or stomach), and 48 controls (12 age-matched autistic children with no GI disease, 20 age-matched children without autism or GI disease, and 16 nonautistic individuals with no family history of autism) were tested using enzyme-linked immunosorbent assays designed to quantitate serum MPO levels. MPO serum concentration of autistic children with GI disease was compared to GI disease severity (including LNH and erythema) and presence of ANCA.Results: We found that a significant number of autistic children with chronic digestive disease had low serum levels of MPO. However, there was no significant relationship between these levels and severity of GI disease, including the presence of ANCA.Discussion: These results suggest a relationship between low MPO levels and GI disease seen in a subpopulation of autism spectrum disorders individuals. MPO concentration may therefore be a useful biomarker for GI disease in this group of autistic children.Keywords: autism spectrum disorders, autism, myeloperoxidase, GI disease, oxidative stres

Tyrosine 331 and phenylalanine 334 in Clostridium perfringens α-toxin are essential for cytotoxic activity

AbstractDifferences in the biological properties of the Clostridium perfringens phospholipase C (α-toxin) and the C. bifermentans phospholipase C (Cbp) have been attributed to differences in their carboxy-terminal domains. Three residues in the carboxy-terminal domain of α-toxin, which have been proposed to play a role in membrane recognition (D269, Y331 and F334), are not conserved in Cbp (Y, L and I respectively). We have characterised D269Y, Y331L and F334I variant forms of α-toxin. Variant D269Y had reduced phospholipase C activity towards aggregated egg yolk phospholipid but increased haemolytic and cytotoxic activity. Variants Y331L and F334I showed a reduction in phospholipase C, haemolytic and cytotoxic activities indicating that these substitutions contribute to the reduced haemolytic and cytotoxic activity of Cbp

From nanoliter to large-scale bioreactors: How integrated technologies bring antibody treatments to patients faster

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Geography, private costs and uptake of screening for abdominal aortic aneurysm in a remote rural area

BACKGROUND: The relationship between geographical location, private costs, health provider costs and uptake of health screening is unclear. This paper examines these relationships in a screening programme for abdominal aortic aneurysm in the Highlands and Western Isles of Scotland, a rural and remote area of over 10,000 square miles. METHODS: Men aged 65–74 (n = 9323) were invited to attend screening at 51 locations in 50 settlements. Effects of geography, deprivation and age on uptake were examined. Among 8,355 attendees, 8,292 completed a questionnaire detailing mode of travel and costs incurred, time travelled, whether accompanied, whether dependants were cared for, and what they would have been doing if not attending screening, thus allowing private costs to be calculated. Health provider (NHS) costs were also determined. Data were analysed by deprivation categories, using the Scottish Indices of Deprivation (2003), and by settlement type ranging from urban to very remote rural. RESULTS: Uptake of screening was high in all settlement types (mean 89.6%, range 87.4 – 92.6%). Non-attendees were more deprived in terms of income, employment, education and health but there was no significant difference between non-attendees and attendees in terms of geographical access to services. Age was similar in both groups. The highest private costs (median £7.29 per man) and NHS screening costs (£18.27 per man invited) were observed in very remote rural areas. Corresponding values for all subjects were: private cost £4.34 and NHS cost £15.72 per man invited. CONCLUSION: Uptake of screening for abdominal aortic aneurysm in this remote and rural setting was high in comparison with previous studies, and this applied across all settlement types. Geographical location did not affect uptake, most likely due to the outreach approach adopted. Private and NHS costs were highest in very remote settings but still compared favourably with other published studies

GroundsWell: Community-engaged and data-informed systems transformation of Urban Green and Blue Space for population health – a new initiative

This is the published version. Available on open access from F1000 Research via the DOI in this record[version 1; peer review: 1 approved].Data availability: No data are available with this article.Natural environments, such as parks, woodlands and lakes, have positive impacts on health and wellbeing. Urban Green and Blue Spaces (UGBS), and the activities that take place in them, can significantly influence the health outcomes of all communities, and reduce health inequalities. Improving access and quality of UGBS needs understanding of the range of systems (e.g. planning, transport, environment, community) in which UGBS are located. UGBS offers an ideal exemplar for testing systems innovations as it reflects place-based and whole society processes, with potential to reduce non-communicable disease (NCD) risk and associated social inequalities in health. UGBS can impact multiple behavioural and environmental aetiological pathways. However, the systems which desire, design, develop, and deliver UGBS are fragmented and siloed, with ineffective mechanisms for data generation, knowledge exchange and mobilisation. Further, UGBS need to be co-designed with and by those whose health could benefit most from them, so they are appropriate, accessible, valued and used well. This paper describes a major new prevention research programme and partnership, GroundsWell, which aims to transform UGBS-related systems by improving how we plan, design, evaluate and manage UGBS so that it benefits all communities, especially those who are in poorest health. We use a broad definition of health to include physical, mental, social wellbeing and quality of life. Our objectives are to transform systems so that UGBS are planned, developed, implemented, maintained and evaluated with our communities and data systems to enhance health and reduce inequalities. GroundsWell will use interdisciplinary, problem-solving approaches to accelerate and optimise community collaborations among citizens, users, implementers, policymakers and researchers to impact research, policy, practice and active citizenship. GroundsWell will be shaped and developed in three pioneer cities (Belfast, Edinburgh, Liverpool) and their regional contexts, with embedded translational mechanisms to ensure that outputs and impact have UK-wide and international application.UK Prevention Research PartnershipHSC Research and Development Office Northern Irelan

Progress and prospects for event tourism research

This paper examines event tourism as a field of study and area of professional practice updating the previous review article published in 2008. In this substantially extended review, a deeper analysis of the field’s evolution and development is presented, charting the growth of the literature, focusing both chronologically and thematically. A framework for understanding and creating knowledge about events and tourism is presented, forming the basis which signposts established research themes and concepts and outlines future directions for research. In addition, the review article focuses on constraining and propelling forces, ontological advances, contributions from key journals, and emerging themes and issues. It also presents a roadmap for research activity in event tourism

The dominant Anopheles vectors of human malaria in Africa, Europe and the Middle East: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>This is the second in a series of three articles documenting the geographical distribution of 41 dominant vector species (DVS) of human malaria. The first paper addressed the DVS of the Americas and the third will consider those of the Asian Pacific Region. Here, the DVS of Africa, Europe and the Middle East are discussed. The continent of Africa experiences the bulk of the global malaria burden due in part to the presence of the <it>An. gambiae </it>complex. <it>Anopheles gambiae </it>is one of four DVS within the <it>An. gambiae </it>complex, the others being <it>An. arabiensis </it>and the coastal <it>An. merus </it>and <it>An. melas</it>. There are a further three, highly anthropophilic DVS in Africa, <it>An. funestus</it>, <it>An. moucheti </it>and <it>An. nili</it>. Conversely, across Europe and the Middle East, malaria transmission is low and frequently absent, despite the presence of six DVS. To help control malaria in Africa and the Middle East, or to identify the risk of its re-emergence in Europe, the contemporary distribution and bionomics of the relevant DVS are needed.</p> <p>Results</p> <p>A contemporary database of occurrence data, compiled from the formal literature and other relevant resources, resulted in the collation of information for seven DVS from 44 countries in Africa containing 4234 geo-referenced, independent sites. In Europe and the Middle East, six DVS were identified from 2784 geo-referenced sites across 49 countries. These occurrence data were combined with expert opinion ranges and a suite of environmental and climatic variables of relevance to anopheline ecology to produce predictive distribution maps using the Boosted Regression Tree (BRT) method.</p> <p>Conclusions</p> <p>The predicted geographic extent for the following DVS (or species/suspected species complex*) is provided for Africa: <it>Anopheles </it>(<it>Cellia</it>) <it>arabiensis</it>, <it>An. </it>(<it>Cel.</it>) <it>funestus*</it>, <it>An. </it>(<it>Cel.</it>) <it>gambiae</it>, <it>An. </it>(<it>Cel.</it>) <it>melas</it>, <it>An. </it>(<it>Cel.</it>) <it>merus</it>, <it>An. </it>(<it>Cel.</it>) <it>moucheti </it>and <it>An. </it>(<it>Cel.</it>) <it>nili*</it>, and in the European and Middle Eastern Region: <it>An. </it>(<it>Anopheles</it>) <it>atroparvus</it>, <it>An. </it>(<it>Ano.</it>) <it>labranchiae</it>, <it>An. </it>(<it>Ano.</it>) <it>messeae</it>, <it>An. </it>(<it>Ano.</it>) <it>sacharovi</it>, <it>An. </it>(<it>Cel.</it>) <it>sergentii </it>and <it>An. </it>(<it>Cel.</it>) <it>superpictus*</it>. These maps are presented alongside a bionomics summary for each species relevant to its control.</p

An observational study showed that explaining randomization using gambling-related metaphors and computer-agency descriptions impeded randomized clinical trial recruitment

Objectives To explore how the concept of randomization is described by clinicians and understood by patients in randomized controlled trials (RCTs) and how it contributes to patient understanding and recruitment. Study Design and Setting Qualitative analysis of 73 audio recordings of recruitment consultations from five, multicenter, UK-based RCTs with identified or anticipated recruitment difficulties. Results One in 10 appointments did not include any mention of randomization. Most included a description of the method or process of allocation. Descriptions often made reference to gambling-related metaphors or similes, or referred to allocation by a computer. Where reference was made to a computer, some patients assumed that they would receive the treatment that was “best for them”. Descriptions of the rationale for randomization were rarely present and often only came about as a consequence of patients questioning the reason for a random allocation. Conclusions The methods and processes of randomization were usually described by recruiters, but often without clarity, which could lead to patient misunderstanding. The rationale for randomization was rarely mentioned. Recruiters should avoid problematic gambling metaphors and illusions of agency in their explanations and instead focus on clearer descriptions of the rationale and method of randomization to ensure patients are better informed about randomization and RCT participation

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570