Cross-clade inhibition of HIV-1 replication and cytopathology by using RNase P-associated external guide sequences

RNase P complexes have been proposed as a novel RNA-based gene interference strategy to inhibit gene expression in human malignancies and infectious diseases. This approach is based on the sequence-specific design of an external guide sequence (EGS) RNA molecule that can specifically hybridize to almost any complementary target mRNA and facilitate its cleavage by the RNase P enzyme component. We designed a truncated RNase P-associated EGS molecule to specifically recognize the U5 region of HIV-1 mRNA and mediate cleavage of hybridized mRNA by the RNase P enzyme. Genes encoding for this U5-EGS (560) molecule, as well as a U5 EGS (560D) antisense control, were cloned into retroviral plasmids and transferred into a CD4(+) T cell line. Transfected cells were exposed to increasing concentrations of HIV-1 clinical isolates from clades A, B, C, and F. Heterogeneous cultures of CD4(+) T cells expressing the U5 EGS (560) molecule were observed to maintain CD4 levels, were devoid of cytopathology, and did not produce HIV p24 gag antigen through 30 days after exposure to all HIV-1 clades at a multiplicity of infection of 0.01. Identical cells expressing the U5 EGS (560D) antisense control molecule underwent a loss of CD4 expression, produced elevated levels of HIV-1, and formed large syncytia similar to untreated cells. When the viral inoculum was increased at the time of exposure (multiplicity of infection = 0.05), the inhibitory effect of the U5 EGS (560) molecule was overwhelmed, but viral-mediated cytopathology and particle production were delayed compared with control cell populations. Viral replication and cytopathology associated with infection of multiple HIV-1 clades can be effectively inhibited in CD4(+) cells expressing the RNase P-associated U5 EGS (560) molecule.     

Translating psychosocial research findings into practice guidelines

Evidence-based practice guidelines are increasingly used by healthcare professionals to guide patient care and effect positive patient outcomes. These guidelines are usually based on laboratory-based parameters and lack the psychosocial dimensions of patient care. The authors describe the process used by a hospital-based interdisciplinary team to successfully develop evidence-based psychosocial guidelines designed to foster hopefulness in pediatric patients with cancer, their families, and their healthcare providers. From these guidelines, 4 clinical care projects were developed and are described in this article.     

Meeting the challenge of continuing education with eLearning

For many of us, the concept of "e" anything invokes a sense of skepticism and even dread. However, the Web and all it has to offer is certainly an integral part of modern life and, once reconciled, offers great opportunities for commerce and knowledge building. One particular area of promise is that of online learning or "eLearning" as it is referred to in the literature. Particularly for sonographers and technologists, the ability to travel to seminars and conferences on hospital budgets and time is a distant memory. Conversely, the pressure to stay current with CE requirements is greater than ever. With the growing phenomena of accreditation and the use of that as standard for quality care, these staff members are under more pressure than ever to maintain their certification. There is also the issue of accountability. What is being done to track employee training and assist in on-going development? How do we know that the program was appropriate for that particular employee and that an adequate ROI was achieved from a learning perspective? With eLearning, the opportunity to track the employee's progress, scores and areas of interest are possible. This can assist the administrator in "managing" the learning within the group and taking an active role in the development of the staff. The ultimate eLearning experience provides the right content at the right time. It motivates people to learn and apply their knowledge and skills to improve their individual and organizational performance. This is achieved by providing learners with easy and immediate access to the content. The design elements of the site should include a friendly format that facilitates easy navigation through the content. Other helpful features are: book-marking that allows the student to return to the last page studied, interactivity, visualization technologies, and feedback throughout the learning experience. The opportunities for the utilization of eLearning in the global medical community are remarkable. eLearning facilitates learning at anytime and anywhere. It reduces the obstacles of time and distance, providing greater equality of opportunity.     

The pathological mechanisms of glycoregulation disturbances in chronic hepatitis B and C

Despite the abundance of reports concerning the increased frequency of diabetes and impaired glucose tolerance in chronic liver diseases, the mechanisms underlying this phenomenon have not been resolved. 30 patients with hepatitis C virus (HCV) infection and 17 with hepatitis B virus (HBV) infection who showed an altered responds to a standard oral glucose tolerance test were investigated in order to evaluate their pancreatic-endocrine features. We have also evaluated 40 patients (20 with HCV infection and 20 with HCB infection) who developed diabetes after diagnosis of liver disease. Patients with HBV infection showed signs of enhanced insulin resistance but overt diabetes develops in those who, in addition to insulin insensitivity, have a relative defect of insulin secretion. In patients with HCV infection the significantly lower plasma insulin and C-peptide levels suggest that impairment of insulin secretion is the main mechanism leading to both glucose intolerance and overt diabetes.     

Tolerance of early diet textures as indicators of recovery from dysphagia after stroke

We undertook this 12-month retrospective cohort study, of 186 teaching hospital inpatients, to determine how tolerance of differing diet textures after a stroke predicts recovery from dysphagia. Outcome measures were insertion of a percutaneous endoscopic gastrostomy (PEG) tube and/or ability to tolerate a normal diet 28 days after the stroke. Likelihood ratios for needing a PEG were highest for intolerance of pureed food. People who tolerated grade 1 fluids (300–600 cP) or thinner, or who tolerated a modified soft diet or better, 7 days after the stroke did not need a PEG. Half (13/26) the people who could not tolerate grade 3 thickened fluids (10,000–12,000 cP) and 52% (13/25) of people who could not tolerate a puree diet 14 days after the stroke needed a PEG. No one who was intolerant of grade 2 thickened fluids (4000–7000 cP) 7 or 14 days after the stroke could tolerate a normal diet and fluids by day 28. If people were tolerating grade 3 thickened fluids at day 7, the proportion tolerating a normal diet at day 28 was 36%. We present similar data for tolerance of differing fluids and diets at each of the measured time points. We suggest a PEG should be considered in people unable to tolerate grade 3 thickened fluids or a puree diet 14 days after their stroke. However, even in these groups, half will recover sufficiently to manage oral feeding.