A murine model of Trypanosoma brucei-induced myocarditis and cardiac dysfunction.

Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). Cardiac symptoms are commonly reported in HAT patients, and intracardiac parasites with accompanying myocarditis have been observed in both natural hosts and animal models of T. brucei infection. However, despite the importance of T. brucei as a cause of cardiac dysfunction and the dramatic socioeconomic impact of African trypanosomiases in sub-Saharan Africa, there are currently no reproducible murine models of T. brucei-associated cardiomyopathy. We present the first clinically relevant, reproducible murine model of cardiac dysfunction in chronic T. brucei infection. Similar to humans, mice showed histological evidence of myocarditis and elevation of serum NT-proBNP. Serum NT-proBNP levels were elevated prior to the development of severe ventricular dysfunction. On flow cytometry, myocarditis was associated with an increase of most myocardial immune cell populations, including multiple T cell and macrophage subsets, corroborating the notion that T. brucei-associated cardiac damage is an immune-mediated event. This novel mouse model represents a powerful and practical tool to investigate the pathogenesis of T. brucei-mediated heart damage and support the development of therapeutic options for T. brucei-associated cardiac disease.

Thinking outside the blood: Perspectives on tissue-resident Trypanosoma brucei.

Trypanosoma brucei is a protozoan parasite that causes human and animal African trypanosomiases (HAT and AAT). In the mammalian host, the parasite lives entirely extracellularly, in both the blood and interstitial spaces in tissues. Although most T. brucei research has focused on the biology of blood- and central nervous system (CNS)-resident parasites, a number of recent studies have highlighted parasite reservoirs in the dermis and adipose tissue, leading to a renewed interest in tissue-resident parasite populations. In light of this renewed interest, work describing tissue-resident parasites can serve as a valuable resource to inform future investigations of tissue-resident T. brucei. Here, we review this body of literature, which describes infections in humans, natural hosts, and experimental animal models, providing a wealth of information on the distribution and biology of extravascular parasites, the corresponding immune response in each tissue, and resulting host pathology. We discuss the implications of these studies and future questions in the study of extravascular T. brucei.

The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex.

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.

'There were more wires than him': the potential for wireless patient monitoring in neonatal intensive care.

BACKGROUND: The neonatal intensive care unit (NICU) can be one of the most stressful hospital environments. Alongside providing intensive clinical care, it is important that parents have the opportunity for regular physical contact with their babies because the neonatal period is critical for parent-child bonding. At present, monitoring technology in the NICU requires multiple wired sensors to track each baby's vital signs. This study describes the experiences that parents and nurses have with the current monitoring methods, and reports on their responses to the concept of a wireless monitoring system. METHODS: Semistructured interviews were conducted with six parents, each of whom had babies on the unit, and seven nurses who cared for those babies. The interviews initially focused on the participants' experiences of the current wired system and then on their responses to the concept of a wireless system. The transcripts were analysed using a general inductive approach to identify relevant themes. RESULTS: Participants reported on physical and psychological barriers to parental care, the ways in which the current system obstructed the efficient delivery of clinical care and the perceived benefits and risks of a wireless system. The parents and nurses identified that the wires impeded baby-parent bonding; physically and psychologically. While a wireless system was viewed as potentially enabling greater interaction, staff and parents highlighted potential concerns, including the size, weight and battery life of any new device. CONCLUSIONS: The many wires required to safely monitor babies within the NICU creates a negative environment for parents at a critical developmental period, in terms of physical and psychological interactions. Nurses also experience challenges with the existing system, which could negatively impact the clinical care delivery. Developing a wireless system could overcome these barriers, but there remain challenges in designing a device suitable for this unique environment.

Intrauterine Zika virus infection of pregnant immunocompetent mice models transplacental transmission and adverse perinatal outcomes.

Zika virus (ZIKV) crosses the placenta and causes congenital disease. Here we develop an animal model utilizing direct ZIKV inoculation into the uterine wall of pregnant, immunocompetent mice to evaluate transplacental transmission. Intrauterine inoculation at embryonic day (E) 10, but not E14, with African, Asian or American strains of ZIKV reduces fetal viability and increases infection of placental and fetal tissues. ZIKV inoculation at E10 causes placental inflammation, placental dysfunction and reduces neonatal brain cortical thickness, which is associated with increased activation of microglia. Viral antigen localizes in trophoblast and endothelial cells in the placenta, and endothelial, microglial and neural progenitor cells in the fetal brain. ZIKV infection of the placenta increases production of IFNß and expression of IFN-stimulated genes 48 h after infection. This mouse model provides a platform for identifying factors at the maternal-fetal interface that contribute to adverse perinatal outcomes in a host with an intact immune system.

Patterns of functional loss among older people: a prospective analysis.

OBJECTIVE: Patterns of capability loss and disability onset among older people were investigated prospectively. BACKGROUND: With aging, the gap between personal capability and environmental demand becomes wider, resulting in higher levels of disability in daily activities. METHODS: Data from a longitudinal, population-based study were obtained for analysis, which recruited a representative sample of 13,004 people aged 65 years and older from five sites in Great Britain. Participants completed a baseline interview during 1990 to 1994 and follow-up interviews after 1, 2, 3, 6, 8, and 10 years. Those who reported full vision, hearing, thinking, locomotion, reaching, and dexterity ability as well as no disability in cooking, housework, shopping, and transportation at baseline were included in a survival analysis. RESULTS: Locomotion was the first ability to be lost, followed by reaching, thinking, hearing, vision, and dexterity. Age at onset of disability was earliest for shopping, then housework, transportation, and cooking. Women were consistently younger at capability loss and disability onset than men except in terms of hearing and cooking. CONCLUSION: These findings suggest that capabilities required for product and service interaction follow a hierarchical pattern of loss, which has practical implications for design. Although interventions to reduce disability in the older population are likely to require changes that address more than one demand, capabilities lost early in old age should take precedence over those lost later. APPLICATION: A potential application of this research is in the development of an overall design strategy to enhance older people's ability to live independently.