The presence of inhibitory RNA elements in the late 3'-untranslated region is a conserved property of human papillomaviruses

Here we have tested the inhibitory activity of the late untranslated region (UTR) of nine different human papillomavirus (HPV) types representing three different genera and six different species. These HPVs include both low-risk and high-risk types. We found that the late UTR of the various HPVs all displayed inhibitory activity, although they inhibited gene expression to various extent. The late UTR from the two distantly related HPV types 1 and 16, which are two different species that belong to different genera, each interacted with a 55 kDa protein. This protein cross-linked specifically to both HPV-1 and HPV-16 late UTR, although it bound more strongly to HPV-16 than to HPV-1, which correlated with the higher inhibitory activity of the HPV-16 late UTR. Mutagenesis experiments revealed that inactivation of two UGUUUGU motifs in the HPV-16 late UTR or two UAUUUAU motifs in the HPV-1 late UTR resulted in loss of binding of p55. In summary, these results demonstrate that the presence inhibitory elements encoding PuU(3-5)Pu-motifs in the HPV late UTR is a conserved property of different HPV types, species and genera, and suggest that these elements play an important role in the viral life cycle.     

Incentives and Disincentives for the Treatment of Depression and Anxiety: A Scoping Review

Objective:

There is widespread support for primary care to help address growing mental health care demands. Incentives and disincentives are widely used in the design of health care systems to help steer toward desired goals. The absence of a conceptual model to help understand the range of factors that influence the provision of primary mental health care inspired a scoping review of the literature. Understanding the incentives that promote and the disincentives that deter treatment for depression and anxiety in the primary care context will help to achieve goals of greater access to mental health care.

Method:

A review of the literature was conducted to answer the question, how are incentives and disincentives conceptualized in studies investigating the treatment of common mental disorders in primary care? A comprehensive search of MEDLINE, PsycINFO, CINAHL, and Google Scholar was undertaken using Arksey and O’Malley’s 5-stage methodological framework for scoping reviews.

Results:

We identified 27 studies. A range of incentives and disincentives influence the success of primary mental health care initiatives to treat depression and anxiety. Six types of incentives and disincentives can encourage or discourage treatment of depression and anxiety in primary care: attitudes and beliefs, training and core competencies, leadership, organizational, financial, and systemic.

Conclusions:

Understanding that there are 6 different types of incentives that influence treatment for anxiety and depression in primary care may help service planners who are trying to promote improved mental health care.     

Cytogenetic studies in non-African Burkitt lymphoma

A particular translocation between chromosomes 8 and 14 has been found repeatedly in cytogenetic studies of Burkitt lymphoma, both of African and non-African origin. We report here our findings in cytogenetic studies of direct tumor preparations from 18 non-African Burkitt lymphoma patients, 9 of whom also had cell lines available for study. A t(8;14) was found in direct tumor material in 10 of the 18 patients. Seven of the 9 cell lines had a t(8;14). A total of 15 patients had either a t(8;14) or a 14q+ present in tumor material and/or cell lines. In addition, 8 patients had a peculiar marker chromosome 1. The t(8;14) was not found in every malignant cell and, where present, it was rarely the sole karyotypic abnormality. The relationship of the t(8;14) to the evolution of the tumor is discussed.     

Induction of sensitivity to activation-induced death in primary CD4+ cells: A role for interleukin-2 in the negative regulation of responses by mature CD4+ T cells

We examine the requirements for converting naive, mature CD4⁺ cells from an activation-induced death (AID)-resistant to a -sensitive phenotype. Priming for sensitivity to AID can be divided into two steps. The first is a mitogen/CD3-dependent, cyclosporin-sensitive signal and the second a cytokine-dependent, cyclosporin-insensitive one. Under these conditions, interleukin (IL)-2, but not IL-4, IL-7 or IL-15, the receptors of which share a common receptor γ chain, is capable of providing the cytokine signal for inducing sensitivity to AID. Increased expression of the low-affinity IL-2Rα chain (CD25) is associated with acquisition of AID sensitivity and antibodies to CD25 block acquisition of AID sensitivity in the presence of IL-2. As with T cell hybridomas, AID is dependent on both CD95 and CD95 ligand (CD95L) expression, but unlike hybridomas, the sensitive and resistant phenotypes of primary CD4⁺ cells cannot be distinguished by levels of CD95 expression, functional CD95L nor the fraction of cells in cycle. The results suggest that the unique function of IL-2 is to regulate proteins, either not important or constitutively regulated in T cell hybridomas, that are essential for cell-autonomous suicide of activated CD4⁺ cells. These experiments provide a mechanism for the recent observations of chronic lymphoproliferation and autoimmune disease in mice with null mutations in IL-2 or CD25.     

The usefulness of dye-penetration studies reexamined

An in vitro study to determine the usefulness of dye-penetration studies was conducted. In part I, teeth were prepared through the foramen and then left open, either apically, coronally, or at both ends. In all cases, the dye did not penetrate the full length of the canal. The only exception was when both ends were left open and the teeth were placed into the dye in an upright position. In part II, a measurable defect in a canal filling the length of the canal was created and left open apically. When the tooth was immersed in dye, the penetration was incomplete. When the air was removed by vacuum pump prior to placement in the dye, the penetration was total. The validity of dye studies that do not consider entrapped air is open to question.     

Addition of an error correction facility to a functioning data management system

The National Institute of Neurological and Communicative Disorders and Stroke conducted the Stroke Data Bank, a prospectively collected database, in collaboration with investigators from four clinical centers. A distributed data entry system was originally designed to permit data entry and editing using microcomputers. As data collection progressed, it became evident that the editing system was inadequate. A central data editing component was added to the system, with responsibility for error correction remaining at the clinical centers. This report summarizes the design of the error correction facility and demonstrates the feasibility of its late implementation.     

The aged male rat as a model for human osteoporosis: Evaluation by nondestructive measurements and biomechanical testing

Summary Effects of androgen deficiency and androgen replacement on bone density, as measured with dual-energy X-ray absorptiometry (DXA) and single photon absorptiometry (SPA), cortical ratio (cortical thickness/outside bone diameter x 100), and biomechanical properties were evaluated in 14-month-old (1 month after orchiectomy (orch) or sham-operation) and in 17-month-old (4 months after orch or sham) male rats. Whole femoral bone mineral content (BMC) and density (BMD) measured with DXA were not significantly decreased 1 month after orch. Whole femoral BMC and BMD were 10% and 8% lower in 4 months after orch (P < 0.01 andP < 0.001, respectively). This decrease was prevented by testosterone replacement. There was an excellent correlation (R = 0.99) between whole femoral BMC and femoral ash weight. Selective scanning of cortical and cancellous sites of the femur showed that both cancellous and cortical BMC and BMD were significantly decreased 4 months after orch. SPA of the right tibia confirmed a 7% decrease in cancellous BMC and BMD 4 months after orch (preventable by testosterone) but not in cortical BMD and BMC. Femoral cortical ratio decreased with age (47 ± 2 in 14-month-old and 40 ± 2 in 17-month-old sham rats versus 63 ± 1 in 6-month-old male rats) due to a continuously enlarging femoral shaft. Androgen deficiency resulted in an even greater decrease of the cortical ratio 4 months after orch (36 ± 2 in 17-month-old orch rats) that was again prevented by testosterone (47 ± 3). These changes in femoral cortical, cancellous density, and cortical ratio did not affect biomechanical properties of the femur as evaluated by torsion testing. The lack of an effect on bone biomechanics was most likely due to the protection afforded by an increased femoral shaft diameter. We conclude that 4 months after orch, aged male orch rats had a lower femoral cortical and cancellous density and a lower cortical ratio without decrease of biomechanical properties of the femoral shaft. Testosterone replacement was effective not only in preventing the decrease of cancellous and cortical density but also in preventing the age-related thinning of the femoral cortex.