Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction.
Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.
Broadly neutralizing antibodies (bnAbs) against HIV-1 are an effective means of preventing transmission. To better understand the mechanisms by which HIV-specific bnAbs naturally develop, we investigated blood and lymphoid tissue in pediatric infection, since potent bnAbs develop with greater frequency in children than adults. As in adults, the frequency of circulating effector T-follicular helper cells (TFH) in HIV infected, treatment naïve children correlates with neutralization breadth. However, major differences between children and adults were also observed both in circulation, and in a small number of tonsil samples. In children, TFH cells are significantly more abundant, both in blood and in lymphoid tissue germinal centers, than in adults. Second, HIV-specific TFH cells are more frequent in pediatric than in adult lymphoid tissue and secrete the signature cytokine IL-21, which HIV-infected adults do not. Third, the enrichment of IL-21-secreting HIV-specific TFH in pediatric lymphoid tissue is accompanied by increased TFH regulation via more abundant regulatory follicular T-cells and HIV-specific CXCR5+ CD8 T-cells compared to adults. The relationship between regulation and neutralization breadth is also observed in the pediatric PBMC samples and correlates with neutralization breadth. Matching neutralization data from lymphoid tissue samples is not available. However, the distinction between infected children and adults in the magnitude, quality and regulation of HIV-specific TFH responses is consistent with the superior ability of children to develop high-frequency, potent bnAbs. These findings suggest the possibility that the optimal timing for next generation vaccine strategies designed to induce high-frequency, potent bnAbs to prevent HIV infection in adults would be in childhood.
Background. Ear, nose, and throat (ENT) diseases are an oft overlooked global health concern. Despite their high prevalence and associated morbidity and mortality, ENT diseases have remained neglected in health care delivery. In Zambia and many other low-income countries, ENT services are characterized by poor funding, unavailable surgical procedures, and erratic supply of essential drugs. Objective. To investigate ENT service provision in Zambia with regard to availability of surgical procedures and supply of essential drugs. Methods. A descriptive cross-sectional survey was conducted using a piloted structured questionnaire between 17 January 2017 and 2 January 2018. Included in the study were the 109 hospitals registered with the Ministry of Health (MoH) across the 10 provinces of Zambia. Results. Of the participating hospitals, only 5.9% (n=1) and 40% (n=2) of Second-Level Hospitals (SLH) and Third-Level Hospitals (TLH), respectively, carried out tympanoplasty, myringotomy, and grommet insertion (M+G). Frontal trephination and external ethmoidectomy were offered in 11.7% (n=2) and 40% (n=2) of SLH and TLH, respectively. While tracheostomy (39.3%, n=24), tonsillectomy (27.9%, n=17), and adenoidectomy (27.9%, n=17) were the most widely performed head and neck procedures, laryngectomy was carried out by 1 hospital. Between 14.8% (n=9) and 36.1% (n=22) of hospitals lacked antibiotic and/or antiseptic ear drops. Despite 96.7% (n=59) of the respondents acknowledging ENT as an important branch of clinical practice, only 15.3% (n=4) of the hospitals had a budget for ENT. Also, 6.6% (n=4) of the respondents thought the discipline of ENT had received enough attention. Conclusion. ENT service delivery in Zambia is limited with regard to performed surgical procedures and availability of essential drugs, necessitating urgent intervention. The findings from this study may be used to direct national policy on the improvement of provision of ENT services in Zambia.
Background The prevalence of anemia in the South African pediatric surgical population is unknown. Anemia may be associated with increased postoperative complications. We are unaware of studies documenting these findings in patients in low‐ and middle‐income countries (LMICs). Aim The primary aim of this study was to describe the association between preoperative anemia and 26 defined postoperative complications, in noncardiac pediatric surgical patients. Secondary aims included describing the prevalence of anemia and risk factors for intraoperative blood transfusion. Method This was a secondary analysis of the South African Paediatric Surgical Outcomes Study, a prospective, observational surgical outcomes study. Inclusion criteria were all consecutive patients aged between 6 months and <16 years, presenting to participating centers during the study period who underwent elective and nonelective noncardiac surgery and had a preoperative hemoglobin recorded. Exclusion criteria were patients aged <6 months, undergoing cardiac surgery, or without a preoperative Hb recorded. To determine whether an independent association existed between preoperative anemia and postoperative complications, a hierarchical stepwise logistic regression was conducted. Results There were 1094 eligible patients. In children in whom a preoperative Hb was recorded 46.2% had preoperative anemia. Preoperative anemia was independently associated with an increased risk of any postoperative complication (odds ratio 2.0, 95% confidence interval: 1.3‐3.1, P = .002). Preoperative anemia (odds ratio 3.6, 95% confidence interval: 1.8‐7.1, P < .001) was an independent predictor of intraoperative blood transfusion. Conclusion Preoperative anemia had a high prevalence in a LMIC and was associated with increased postoperative complications. The main limitation of our study is the ability to generalize the results to the wider pediatric surgical population, as these findings only relate to children in whom a preoperative Hb was recorded. Prospective studies are required to determine whether correction of preoperative anemia reduces morbidity and mortality in children undergoing noncardiac surgery.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.