Breast milk transmission of flaviviruses in the context of Zika virus: A systematic review

Background

Since the Zika virus epidemic in the Americas began in 2015, Zika virus transmission has occurred throughout the Americas. However, limited information exists regarding possible risks of transmission of Zika virus and other flaviviruses through breast feeding and human milk. We conducted a systematic review of the evidence regarding flaviviruses detection in and transmission through milk, specifically regarding Zika virus, Japanese encephalitis virus, tick‐borne encephalitis virus, Powassan virus, West Nile virus, dengue virus, and yellow fever virus.

Methods

Medline, Embase, Global Health, CINAHL , Cochrane Library, Scopus, Popline, Virtual Health Library, and WorldCat were searched through June 2017. Two authors independently screened potential studies for inclusion and extracted data. Human and nonhuman (animal) studies describing: 1) confirmed or suspected cases of mother‐to‐child transmission through milk; or 2) the presence of flavivirus genomic material in milk.

Results

Seventeen studies were included, four animal models and thirteen observational studies. Dengue virus, West Nile virus, and Zika virus viral ribonucleic acid was detected in human milk, including infectious Zika virus and dengue virus viral particles. Human breast‐feeding transmission was confirmed for only yellow fever virus. There was evidence of milk‐related transmission of dengue virus, Powassan virus, and West Nile virus in animal studies.

Conclusions

Because the health advantages of breast feeding are considered greater than the potential risk of transmission, the World Health Organization recommends that mothers with possible or confirmed Zika virus infection or exposure continue to breast feed. This review did not identify any data that might alter this recommendation.

     

Brain connectivity during verbal working memory in children and adolescents

Working memory (WkM) is a fundamental cognitive process that serves as a building block for higher order cognitive functions. While studies have shown that children and adolescents utilize similar brain regions during verbal WkM, there have been few studies that evaluate the developmental differences in brain connectivity. Our goal was to study the development of brain connectivity related to verbal WkM in typically developing children and adolescents. Thirty‐five healthy children and adolescents, divided into three groups: 9–12 (children), 13–16 (young adolescents), and 17–19 (older adolescents) years, were included in this functional magnetic resonance imaging (fMRI) study. The verbal WkM task involved a modified Sternberg item recognition paradigm using three different loads. Brain connectivity analysis was performed using independent component analyses and regressing the components with the design matrix to determine task‐related networks. Connectivity analyses resulted in four components associated solely with encoding, four solely with recognition and two with both. Two networks demonstrated age‐related differences with respect to load, (1) the left motor area and right cerebellum, and 2) the left prefrontal cortex, left parietal lobe, and right cerebellum. Post hoc analyses revealed that the first network showed significant effects of age between children and the two older groups. There was increasing connectivity with increasing load for adolescents. The second network demonstrated age‐related differences between children and older adolescents. Children have higher task‐related connectivity at lower loads, but they tend to equalize with the adolescents with higher loads. Finally, a non‐load related network involving the orbital frontal and anterior cingulate cortices showed less connectivity in children. Hum Brain Mapp 35:698–711, 2014. © 2012 Wiley Periodicals, Inc.     

Operationalizing a simulation program: Practical information for leadership

Failure to ensure organizational readiness for curricular integration of simulation can result in a costly and ineffective simulation program. Organizational leaders who are aware of the principles of changemaker leadership and specific operational considerations are best positioned to ensure a quality simulation program. To assist these leaders, this article provides practical information derived from dissection of the Standard of Best Practice: Simulation^SM: Operations, including topics of strategic planning, financial resources, expert personnel, resource management systems, policies and procedures, and systems integration. Additionally, an introduction to a foundational tool to spearhead change is offered, and characteristics of the changemaker leader needed to develop and sustain an effective and efficient simulation program are highlighted. Understanding the criteria necessary for effective simulation operations and early recognition of the conditions and variables that can influence organizational culture is of utmost importance to ensure programmatic success.     

Enlarging skull fractures in children

Large skull fractures are conventionally followed radiographically until healing occurs. Fractures which enlarge or remain unhealed are commonly termed leptomeningeal cysts or growing skull fractures. This study of ten children with this injury and a review of the literature shows that a true leptomeningeal cyst is seldom present and that skull fractures do not grow. Moreover, careful history-taking and physical examination will correctly identify all enlarging or unhealed skull fractures of childhood without the need for plain radiographs or computed tomography of the skull.     

Training graduate-level pediatric psychology researchers at Case Western Reserve University: meeting the challenges of the new millennium

OBJECTIVE: To describe the challenges in training graduate-level pediatric psychology researchers for successful careers and to discuss solutions. METHODS: We reviewed experiences in training graduate students at Case Western Reserve University to identify key challenges in research training and potential strategies to meet them. RESULTS: We identified the following key challenges: stimulating graduate students' career interest in pediatric psychology research; teaching students about the pragmatic challenges of conducting research in pediatric settings, specialized research design, and data analytic issues; helping students to develop essential research skills; developing opportunities for student research-related collaborations; helping students develop professional identities as researchers; and developing and supporting their research careers beyond graduate school. CONCLUSIONS: Useful strategies for meeting these challenges include involving an interdisciplinary faculty in research training; developing specialized training methods that focus on critical research skills such as writing and data analysis; peer support; and involvement with multiple mentors who are successful researchers. Pediatric psychologists should also develop opportunities for the next generation of researchers by facilitating research job options and leadership opportunities.     

Control of Borrelia burgdorferi-specific CD4+-T-cell effector function by interleukin-12- and T-cell receptor-induced p38 mitogen-activated protein kinase activity

Infection with Borrelia burgdorferi, the causative agent of Lyme disease, results in a Th1 response and proinflammatory cytokine production. Mice deficient for MKK3, an upstream activator of p38 mitogen-activated protein (MAP) kinase, develop a lower Th1 response and exhibit an impaired ability to produce proinflammatory cytokines upon infection with the spirochete. We investigated the contribution of p38 MAP kinase activity in gamma interferon (IFN-gamma) production in CD4+ T cells in response to specific antigen through T-cell receptor (TCR)- and interleukin-12 (IL-12)-mediated signals. The specific inhibition of p38 MAP kinase in T cells and the administration of a pharmacological inhibitor of the kinase during the course of infection with the spirochete resulted in reduced levels of IFN-gamma in the sera of infected mice. Our results also demonstrate that although p38 MAP kinase activity is not required for the differentiation of B. burgdorferi-specific CD4+ T cells, the production of IFN-gamma by Th1 effector cells is regulated by the kinase. Both TCR engagement and IL-12 induced the production of the Th1 cytokine through the activation of the p38 MAP kinase pathway. Thus, the inhibition of this pathway in vitro resulted in decreased levels of IFN-gamma during restimulation of B. burgdorferi-specific T cells in response to anti-CD3 and IL-12 stimulation. These results clarify the specific contribution of the p38 MAP kinase in the overall immune response to the spirochete and its role in the effector function of B. burgdorferi-specific T cells.     

Redox regulation of reactive oxygen species-induced p38 MAP kinase activation and barrier dysfunction in lung microvascular endothelial cells

Reactive oxygen species (ROS)-mediated compromise of endothelial barrier integrity has been implicated in a number of pulmonary disorders, including adult respiratory distress syndrome, pulmonary edema, and vasculitis. The mechanisms by which ROS increase endothelial permeability are unclear. We hypothesized that ROS-induced changes in cellular redox status (thiols) may contribute to endothelial barrier dysfunction. To test this hypothesis, we used N-acetylcysteine (NAC) and diamide to modulate intracellular levels of cellular glutathione (GSH) and investigated hydrogen peroxide (H(2)O(2))-mediated mitogen-activated protein kinase (MAPK) activation and transendothelial electrical resistance (TER). Exposure of bovine lung microvascular endothelial cells (BLMVECs) to H(2)O(2), in a dose- and time-dependent fashion, increased endothelial permeability. Pretreatment of BLMVECs with NAC (5 mM) for 1 h resulted in partial attenuation of H(2)O(2)-induced TER (a measure of increase in permeability) and GSH. Furthermore, treatment of BLMVECs with diamide, which is known to reduce the intracellular GSH, resulted in significant reduction in TER, which was prevented by NAC. To understand further the role of MAPKs in ROS-induced barrier dysfunction, we examined the role of extracellular signal-regulated kinase (ERK) and p38 MAPK on H(2)O(2)- and diamide-mediated permeability changes. Both H(2)O(2) and diamide, in a dose-dependent manner, activated ERK and p38 MAPK in BLMVECs. However, SB203580, an inhibitor of p38 MAPK, but not PD98059, blocked H(2)O(2)- and diamide-induced TER. Also, NAC prevented H(2)O(2)- and diamide-induced p38 MAPK, but not ERK activation. These results suggest a role for redox regulation of p38 MAPK in ROS-dependent endothelial barrier dysfunction.