Abstract. Cryptosporidium is a major cause of diarrhea in children in developing countries. However, there is no vaccine available and little is known about immune responses to protective antigens. We investigated antibody responses to p23, a putative vaccine candidate, in children in Bangladesh with cryptosporidiosis and diarrhea (cases) and uninfected children with diarrhea (controls), and p23 gene polymorphisms in infecting species. Serum IgM, IgG, and IgA responses to p23 were significantly greater in cases than controls after three weeks of follow-up. Cases with acute diarrhea had significantly greater serum IgA and IgM responses than those with persistent diarrhea, which suggested an association with protection from prolonged disease. The p23 sequences were relatively conserved among infecting species and subtype families. Although most children were infected with Cryptosporidium hominis, there was a cross-reactive antibody response to C. parvum antigen. These results support further development of p23 as a vaccine candidate.
Running Title: Boston DeclarationWord Count: 689 (not including the table) 2 Nearly three out of every four deaths globally in 2017 were caused by non-communicable diseases (NCDs). 1 Many countries have made progress reducing NCD risk factors such as tobacco use, hyperlipidemia, and hypertension, but no countries have successfully reversed the increasing trends in diabetes prevalence and mortality from diabetes is increasing. 1 This represents a massive global health failure considering the fact that type 2 diabetes is largely preventable with lifestyle modification and that cost-effective treatments exist for both type 2 and type 1 diabetes. 2 Specific concern is needed for type 1 diabetes, which without insulin, it is fatal.In parallel, forced migration has reached a record high with 68.5 million people displaced from their homes around the world, 85% being hosted in low or middle-income countries such as, Uganda, Lebanon, and Pakistan, and 65% occurring in protracted refugee situations. 3 In addition, there are over 100 million conflict-affected non-displaced people and 175 million people who are affected by natural disasters annually. 4 These individuals are particularly vulnerable in crises due to disrupted health services and unpredictable-and often unhealthy-food supplies, which may exacerbate their condition and lead to complications.To date, diabetes and other NCDs have largely been underserved in humanitarian settings. 5,6,7 The true scope of the problem has not been established and it is not known which interventions are efficacious, feasible, and cost-effective in these contexts. With respect to type 1 diabetes, arguably the most immediately life-threatening NCD, the supply and cost of insulin, blood glucose monitoring and diagnostic tools are barriers for both humanitarian responders and their host countries, as well as patient adherence, life expectancy, quality of life, follow-up and provider training in diabetes care.In order to begin to address these major gaps, on 4-5 April 2019, Harvard University convened a meeting of humanitarian and other actors in global health to discuss the immediate needs and barriers to tackling diabetes in humanitarian crises, and to adopt a unified, action-oriented agenda to address this pressing global health issue (http://globalendocrinology.bwh.harvard.edu/symposium). Whilst it was recognised that there are substantial gaps in care for diabetes in all low-resource settings, 8 not just humanitarian crises, and that many other NCDs (e.g., cardiovascular disease, chronic obstructive pulmonary disease and asthma) are also prevalent globally and inadequately addressed in humanitarian settings, 9 we chose to prioritize efforts on diabetes in humanitarian crises, for the following reasons:First, because people with type 1 diabetes who cannot access insulin and continuity of care in a crisis are at acute risk of death. The principles of the Humanitarian Charter and United Nations Universal Declaration of Human Rights include the right to life with dignity. 10 The human rig...
Rationale Although aligning care with patient goals is fundamental to critical care, this process is often delayed and leads to conflict among patients, families, and intensive care unit (ICU) teams. Interprofessional collaboration within ICU teams is an opportunity to improve goal-aligned care, yet this collaboration is poorly understood. A better understanding of how ICU team members work together to provide goal-aligned care may identify new strategies for improvement. Objectives Transactive memory systems is a theory of group mind that explains how high-performing teams use a shared memory and collective cognition. We applied this theory to characterize the process of interprofessional collaboration within ICU teams and its relationship with goal-aligned care. Methods We conducted a secondary analysis of focus group ( n = 10) and semistructured interview ( n = 8) transcripts, gathered during a parent study at two academic medical centers on the process of ICU care delivery in acute respiratory failure. Participants ( N = 70) included interprofessional ICU and palliative care team members, surrogates, and patient survivors. We used directed content analysis, applying transactive memory systems theory and its major components (specialization, coordination, credibility) to examine ICU team collaboration. Results Participants described each ICU profession as having a specialized role in aligning care with patient goals. Different professions have different opportunities to gather knowledge about patient goals and priorities, which results in dispersion of this knowledge among different team members. To share and use this dispersed knowledge, ICU teams rely on an informal coordination process and “side conversations.” This process is a workaround for formal channels (e.g., health records, interprofessional rounds) that do not adequately convey knowledge about patient goals. This informal process does not occur if team members are discouraged from asserting their knowledge because of hierarchy or lack of psychological safety. Conversely, coordination succeeds when team members recognize each other as credible sources of valued knowledge. Conclusions We found that ICU team members work together to align care with patient goals and priorities, using transactive memory systems. The successful function of these systems can be disrupted or promoted by ICU organizational and cultural factors, which are potential targets for efforts to increase goal-aligned care.
The profile of the intestinal microbiota is known to be altered in malnourished young children in low- and middle-income countries. However, there are limited studies longitudinally evaluating the intestinal microbiota in malnourished young children in resource-limited settings over the first two years of life. In this longitudinal pilot study, we determined the effect of age, residential location, and intervention on the composition, relative abundance, and diversity of the intestinal microbiota in a representative sample of children under 24 months of age with no diarrhea in the preceding 72 h in the urban and rural areas of Sindh, Pakistan nested within a cluster-randomized trial evaluating the effect of zinc and micronutrients on growth and morbidity (ClinicalTrials.gov Identifier: NCT00705445). The major findings were age-related with significant changes in alpha and beta diversity with increasing age. There was a significant increase in the relative abundance of the Firmicutes and Bacteroidetes phyla and a significant decrease in that of the Actinobacteria and Proteobacteria phyla (p < 0.0001). There were significant increases in the relative abundances of the major genera Bifidobacterium, Escherichia/Shigella and Streptococcus (p < 0.0001), and no significant change in the relative abundance of Lactobacillus. Using the LEfSE algorithm, differentially abundant taxa were identified between children in the first and second years of age, between those residing in rural and urban areas, and those who received different interventions at different ages from 3 to 24 months. The numbers of malnourished (underweight, wasted, stunted) or well-nourished children at each age, in each intervention arm, and at urban or rural sites were too small to determine if there were significant differences in alpha or beta diversity or differentially abundant taxa among them. Further longitudinal studies with larger numbers of well-nourished and malnourished children are required to fully characterize the intestinal microbiota in this region.
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