Immunologic changes are detectable in the peripheral blood transcriptome of clinically asymptomatic Chagas cardiomyopathy patients.

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected parasitic disease that affects approximately 6 million individuals worldwide. Of those infected, 20-30% will go on to develop chronic Chagas cardiomyopathy (CCC), and ultimately many of these individuals will progress to advanced heart failure. The mechanism by which this progression occurs is poorly understood, as few studies have focused on early CCC. In this study, we sought to understand the physiologic changes associated with T. cruzi infection and the development of CCC. We analyzed gene expression in the peripheral blood of asymptomatic Chagas patients with early structural heart disease, Chagas patients without any signs or symptoms of disease, and Chagas-negative patients with and without early structural heart disease. Our analysis shows that early CCC was associated with a downregulation of various peripheral immune response genes, with gene expression changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes were distinct from those of early cardiomyopathy in Chagas-negative patients, suggesting that the processes mediating CCC may be unique from those mediating progression to other cardiomyopathies. This work highlights the importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease. The changes we have identified may serve as biomarkers of progression and could inform strategies for the treatment of CCC in its early stages, before significant cardiac damage has occurred.

In vitro model of postoncosphere development, and in vivo infection abilities of Taenia solium and Taenia saginata.

Taenia solium is known to cause human cysticercosis while T. saginata does not. Comparative in vitro and in vivo studies on the oncosphere and the postoncospheral (PO) forms of T. solium and T. saginata may help to elucidate why cysticercosis can occur from one and not the other. The aim of this study was to use in vitro culture assays and in vivo models to study the differences in the development of the T. solium and T. saginata oncosphere. Furthermore, this study aimed to evaluate the expression of cytokines and metalloproteinases (MMPs) in human peripheral blood mononuclear cells (PBMCs), which were stimulated by these oncospheres and PO antigens. T. solium and T. saginata activated oncospheres (AO) were cultured in INT-407 and HCT-8 intestinal cells for 180 days. The T. solium began to die while the T. saginata grew for 180 days and developed to cysticerci in INT-407 cells. Rats were inoculated intracranially with AO and PO forms of either T. saginata or T. solium. Rats infected with T. solium AO and PO forms developed neurocysticercosis (NCC), while those infected with the T. saginata did not. Human PMBCs were stimulated with antigens of AO and PO forms of both species, and the production of cytokines and metalloproteinases (MMPs) was measured. The T. solium AO antigen stimulated a higher production of IL-4, IL-5, IL-13, IFN-γ, and IL-2 cytokines compared to T. saginata AO. In the PO form, the T. saginata PO antigen increased the production of IL-4, IL-5, IL-13, IFN-γ, IL-1ß, IL-6, IL-10, TNF-α and IL-12 cytokines compared to T. solium, suggesting that this global immune response stimulated by different forms could permit survival or destruction of the parasite depending of their life-cycle stage. Regarding MMPs, T. solium AO antigen stimulated a higher production of MMP-9 compared to T. saginata AO antigen, which may be responsible for altering the permeability of intestinal cells and facilitating breakdown of the blood-brain barrier during the process of invasion of host tissue.

Preventing ventilator-associated pneumonia in children: an evidence-based protocol.

Ventilator-associated pneumonia, the second most common hospital-acquired infection in pediatric intensive care units, is linked to increased morbidity, mortality, and lengths of stay in the hospital and intensive care unit, adding tremendously to health care costs. Prevention is the most appropriate intervention, but little research has been done in children to identify necessary skills and strategies. Critical care nurses play an important role in identification of risk factors and prevention of ventilator-associated pneumonia. A care bundle based on factors, including evidence regarding the pathophysiology and etiology of pneumonia, mechanical ventilation, duration of ventilation, and age of the child, can offer prompts and consistent prevention strategies for providers caring for children in the pediatric intensive care unit. Following the recommendations of the Centers for Disease Control and Prevention and adapting an adult model also can support this endeavor. Ultimately, the bedside nurse directs care, using best evidence to prevent this important health care problem.

Psychiatric patients' comprehension of Miranda rights.

Seventy-five psychiatric inpatients were evaluated with respect to their Miranda-related abilities using Grisso's (1998, Instruments for assessing understanding and appreciation of Miranda rights. Sarasota, FL: Professional Resource Press) instruments and Goldstein's (2002, Revised instruments for assessing understanding and appreciation of Miranda rights) revision to determine: whether different versions of Miranda warnings translate into differences in understanding; the influence of psychiatric symptoms, diagnostic categories, and IQ upon Miranda comprehension; and the relative performance of persons with psychiatric impairment on Miranda-relevant abilities. Results indicated that although the Miranda language used in Goldstein's revision generally showed lower grade reading levels and higher reading ease scores than Grisso's original instruments, this did not translate into improved understanding. In addition, psychiatric symptoms were negatively correlated with Miranda comprehension, even after controlling for IQ. Finally, results revealed that psychiatric patients' understanding and appreciation was substantially impaired compared to Grisso's adult validation samples, and was roughly comparable to Grisso's juvenile validation sample. Implications of these results for policy reform are discussed.

Predictor variables in competency to stand trial decisions.

Clinicians possess significant discretion in competency to stand trial assessment. Therefore, it is paramount to explore the contribution of individual variables to ensure that the decision-making process is devoid of bias and solely relates to the legal criterion. To test for the possibility of bias in clinical decision-making, we examined the predictive efficiency of clinical, criminological, and sociodemographic variables in a sample of 468 criminal defendants referred for competency evaluations. Only clinical diagnostic variables and employment status were significant predictors. This finding supports the idea that examiner decisions of competency appear to be unbiased and relate primarily to a defendant's functional ability.