IL-33-mediated protection against experimental cerebral malaria is linked to induction of Type 2 innate lymphoid cells, M2 macrophages and regulatory T cells

Author Summary Cerebral malaria (CM) caused by the parasite Plasmodium sp . is a fatal disease, especially in children. Currently there is no effective treatment. We report here our investigation on the role of a recently discovered cytokine IL-33, in treating experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. IL-33 protects the mice against ECM. The protection is accompanied by a reduction of Th1 response and the enhancement of type 2 cytokine response. We also found that IL-33 mediates its protective effect by inducing a population of type 2 innate lymphoid cells (ILC2), which then polarize macrophages to alternatively-activated phenotypes (M2). M2 in turn expand regulatory T cells (Tregs) which suppress the deleterious Th1 response. Our report therefore reveals hitherto unrecognised mechanisms of the regulation of ECM and provide a novel function of IL-33

CD4+ Natural Regulatory T Cells Prevent Experimental Cerebral Malaria via CTLA-4 When Expanded In Vivo

Studies in malaria patients indicate that higher frequencies of peripheral blood CD4+ Foxp3+ CD25+ regulatory T (Treg) cells correlate with increased blood parasitemia. This observation implies that Treg cells impair pathogen clearance and thus may be detrimental to the host during infection. In C57BL/6 mice infected with Plasmodium berghei ANKA, depletion of Foxp3+ cells did not improve parasite control or disease outcome. In contrast, elevating frequencies of natural Treg cells in vivo using IL-2/anti-IL-2 complexes resulted in complete protection against severe disease. This protection was entirely dependent upon Foxp3+ cells and resulted in lower parasite biomass, impaired antigen-specific CD4+ T and CD8+ T cell responses that would normally promote parasite tissue sequestration in this model, and reduced recruitment of conventional T cells to the brain. Furthermore, Foxp3+ cell-mediated protection was dependent upon CTLA-4 but not IL-10. These data show that T cell-mediated parasite tissue sequestration can be reduced by regulatory T cells in a mouse model of malaria, thereby limiting malaria-induced immune pathology

Tailored Print Communication and Telephone Motivational Interviewing Are Equally Successful in Improving Multiple Lifestyle Behaviors in a Randomized Controlled Trial

Background: Computer tailoring and motivational interviewing show promise in promoting lifestyle change, despite few head-to-head comparative studies. Purpose: Vitalum is a randomized controlled trial in which the efficacy of these methods was compared in changing physical activity and fruit and vegetable consumption in middle-aged Dutch adults. Methods: Participants (n?=?1,629) were recruited via 23 general practices and randomly received either four tailored print letters, four motivational telephone calls, two of each type of intervention, or no information. The primary outcomes were absolute change in self-reported physical activity and fruit and vegetable consumption. Results: All three intervention groups (i.e., the tailored letters, the motivational calls, and the combined version) were equally and significantly more effective than the control group in increasing physical activity (hours/day), intake of fruit (servings/day), and consumption of vegetables (grams/day) from baseline to the intermediate measurement (week 25), follow-up 1 (week 47) and 2 (week 73). Effect sizes (Cohen's d) ranged from 0.15 to 0.18. Participants rated the interventions positively; interviews were more positively evaluated than letters. Conclusions: Tailored print communication and telephone motivational interviewing or their combination are equally successful in changing multiple behaviors. © 2010 The Author(s)

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research

Minimally invasive direct access heart valve surgery

We review our experience with minimally invasive direct access (MIDA) heart valve surgery in 518 patients. Two hundred fifty-two patients underwent MIDA aortic valve replacement (AVR) or repair and 266 underwent MIDA mitral valve repair or replacement. Among the 250 AVRs, 157 (63%) were men, aged 63.2 ± 14.6 years, NYHA functional Class 2.4 ± 0.8. The surgical approach was right parasternal in 36 (14%) or upper hemisternotomy in 216 (86%). There were four (2%) operative deaths. Perioperative complications included 14 (5.6%) reexplorations for bleeding, 7 (3%) chest wound infections, 5 (2%) strokes, and 1 (0.4%) external iliac vein injury. Follow-up was complete in 193 (77%) patients, with a mean follow-up of 12 ± 8 months. Late complications included 2 (0.8%) nonfatal myocardial infarctions, 4 (2%) reoperations for, respectively, 2 pericardial complications, 1 paravalvar leak, and 1 infected valve. There were five (2%) late deaths from congestive heart failure, pneumonia, hemorrhage, aneurysm, and cancer. Mean follow-up NYHA Class was 1.4 ± 0.6. For the 266 mitral patients, 145 (54.5%) were men, age 58.7 ± 13.6 years, functional Class 2.3 ± 0.5. The surgical approach was right parasternal in 195 (73%), lower hemisternotomy in 53 (20%), right submammary thoracotomy in 9 (3.4%), or full sternotomy through a small skin incision in 9 (3.4%). There were 2 (0.8%) operative deaths. Perioperative complications included 4 (1.5%) reoperations for bleeding, 4 (1.5%) strokes, and 5 (2%) wound infections, and 3 (1%) ascending aortic complications. Follow-up was complete in 202 (76%) patients with a mean follow-up of 9.5 ± 6.4 months. Late complications included one (0.4%) nonfatal myocardial infarction and three (1%) reoperations all converting repairs to replacements. There were three (1%) late deaths from suicide, pneumonia, and sudden death, respectively. Mean follow-up NYHA functional Class was 1.3 ± 0.5. We conclude that MIDA heart valve surgery is safe and effective for the majority of patients requiring isolated elective aortic or mitral valve surgery.link_to_subscribed_fulltex