Human CD4+ Memory T Cells Can Become CD4+IL-9+ T Cells

Background: IL-9 is a growth factor for T- and mast-cells that is secreted by human Th2 cells. We recently reported that IL-4+TGF-β directs mouse CD4+CD25−CD62L+ T cells to commit to inflammatory IL-9 producing CD4+ T cells. Methodology/Principal Findings: Here we show that human inducible regulatory T cells (iTregs) also express IL-9. IL-4+TGF-β induced higher levels of IL-9 expression in plate bound-anti-CD3 mAb (pbCD3)/soluble-anti-CD28 mAb (sCD28) activated human resting memory CD4+CD25−CD45RO+ T cells as compared to naïve CD4+CD25−CD45RA+ T cells. In addition, as compared to pbCD3/sCD28 plus TGF-β stimulation, IL-4+TGF-β stimulated memory CD4+CD25−CD45RO+ T cells expressed reduced FOXP3 protein. As analyzed by pre-amplification boosted single-cell real-time PCR, human CD4+IL-9+ T cells expressed GATA3 and RORC, but not IL-10, IL-13, IFNγ or IL-17A/F. Attempts to optimize IL-9 production by pbCD3/sCD28 and IL-4+TGF-β stimulated resting memory CD4+ T cells demonstrated that the addition of IL-1β, IL-12, and IL-21 further enhance IL-9 production. Conclusions/Significance: Taken together these data show both the differences and similarities between mouse and human CD4+IL9+ T cells and reaffirm the powerful influence of inflammatory cytokines to shape the response of activated CD4+ T cells to antigen

Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources’ Allocation

Background. Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. Methods. SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. Results. There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate- multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent"cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19- related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. Conclusions. In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A study of natural killer cells in allogeneic solid organ transplantation

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The Changing Landscape of Acute Kidney Injury in Pregnancy from an Obstetrics Perspective

Pregnancy-related acute kidney injury (PR-AKI) is a heterogeneous disorder with multiple aetiologies that can occur at any time throughout pregnancy and the post-partum period. PR-AKI is an important obstetric complication that is associated with significant maternal and foetal morbidity and mortality. Although there has been an overall decline in the incidence of PR-AKI worldwide, a recent shift in the occurrence of this disease has been reported. Following improvements in obstetric care, PR-AKI incidence has been reduced in developing countries, whereas an increase in PR-AKI incidence has been reported in developed countries. Awareness of the physiological adaptations of the renal system is essential for the diagnosis and management of kidney impairment in pregnancy. In this review we scrutinize the factors that have contributed to the changing epidemiology of PR-AKI and discuss challenges in the diagnosis and management of acute kidney injury (AKI) in pregnancy from an obstetrics perspective. Thereafter we provide brief discussions on the diagnostic approach of certain PR-AKI aetiologies and summarize key therapeutic measures

'It gives you the skills of how you can cope' : exploring the self-reported experience of patients receiving in-centre haemodialysis on participating in chosen art activities

BACKGROUND: Increasing numbers of patients are receiving dialysis, particularly in high-income countries. Patients receiving haemodialysis often experience fatigue, anxiety, depression and boredom. It is suggested that arts activities could have a therapeutic effect. OBJECTIVE: This study aimed to explore patients' perspectives of participating while on dialysis in chosen arts and creative living activities provided by tutors at the bedside. DESIGN: Qualitative semi-structured interviews in the interpretive tradition were conducted, with thematic analysis. SETTING AND PARTICIPANTS: Fifteen patients of different ages, genders and ethnicities who participated in an arts activity while receiving haemodialysis in an inner-city dialysis unit in England were included in this study. RESULTS: Participants reported positive experiences of engaging in art activities. Their views on the value of the activities were grouped into five themes: diversion from receiving haemodialysis, a sense of achievement, contribution to a more positive self-identity, increased confidence and motivation and a therapeutic talking relationship. Participants suggested that patient peer promotion of the activities could increase uptake, with patient choice of activity seen as important. CONCLUSIONS: Participation in a chosen arts activity while receiving haemodialysis was perceived by patients to have positive psychosocial effects. We theorize three potential explanatory mechanisms for these effects: That the experience of participating in the activities engendered positive psychological states of 'being in the flow'; enhanced self-esteem to add to personal coping mechanisms; and offered additional facets to the patient's identity that countered the stigmatizing effect of receiving dialysis. PATIENT OR PUBLIC CONTRIBUTION: Patients and public representatives advised on the design, research methods and tools