Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4⁺ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4⁺ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.     

Step training improves the speed of voluntary step initiation in aging

BACKGROUND: Falls related to balance dysfunction are among the major problems of older individuals. The timing characteristics of protective voluntary stepping are critically related to effective balance recovery and are often delayed and slowed with age. This study investigated the influence of step training on the timing characteristics of voluntary step initiation in younger and older adults. METHODS: Voluntary reaction time stepping was evaluated before and after training in 12 younger adults and 8 healthy community-dwelling older adults who performed a 3-week regimen of either twice weekly induced step training (destabilizing large waist pulls) or voluntary step practice to a somatosensory reaction stimulus cue (nondestabilizing small waist pulls). RESULTS: Overall, the first step initiation times were slower for the older than for the younger subjects for both the somatosensory reaction stimulus cue task and an auditory transfer cue task. Step completion time was completed earlier for the young posttraining subjects, and older subjects generally had a longer step length. Training resulted in significant reductions in step initiation timing for the old (17%) and young (15%) subjects. Across age groups, the induced training group showed greater reductions in step initiation time than the voluntary practice group for the auditory transfer cue task. CONCLUSIONS: A 3-week period of either voluntary or waist-pull-induced step training reduced step initiation time in older and younger adults. Moreover, compared with voluntary step practice, induced step training resulted in a significantly greater improvement in reaction time stepping for an auditory transfer cue task. At least in the short term, such step training has the potential to help older adults perform more like younger adults in their step initiation timing.     

Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro.

A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies.     

No door to lock: victimization among homeless and marginally housed persons

BACKGROUND: Homeless persons experience high rates of sexual and physical assault; homeless women are thought to be at highest risk. To determine the prevalence, distribution, and factors associated with sexual and physical assault, we surveyed homeless and marginally housed adults in San Francisco, Calif. METHODS: We interviewed 2577 respondents about their history of recent sexual and physical assault, housing history, sexual practices, substance use, health status, and criminal justice history. The main outcome measures were self-reported sexual and physical assault in the previous 12 months. RESULTS: Overall, 32.3% of women, 27.1% of men, and 38.1% of transgendered persons reported a history of either sexual or physical assault in the previous year; 9.4% of women, 1.4% of men, and 11.9% of transgendered persons reported sexual assault, and 30.6% of women, 26.6% of men, and 33.3% of transgendered persons reported physical assault. In multivariate models, being homeless (as opposed to marginally housed) was associated with sexual assault for women, but not for men (adjusted odds ratio for homeless women, 3.4 [1.2-9.7]). Housing status was not associated with physical assault for women or men. Mental illness and sex work were both common and associated with high rates of assault in multivariate analyses. CONCLUSIONS: Sexual and physical assault are common experiences for homeless and marginally housed persons. Housing is associated with lower rates of sexual assault among women. Strategies to decrease sexual and physical assault and its consequences are needed in this population.     

REVIEW OF NUTRITIONAL SUPPLEMENTS FOR THE TREATMENT OF BIPOLAR DEPRESSION

Many patients view psychotropics with skepticism and fear and view nutritional supplements as more consistent with their values and beliefs. The purpose of this review was to critically evaluate the evidence base for nutritional supplements in the treatment of bipolar depression (BD). A literature search for all randomized, controlled clinical trials using nutritional supplements in the treatment of BD was conducted via PubMed and Ovid MEDLINE computerized database. The studies were organized into essential nutrients/minerals, nonessential nutrients, and combinations of nutritional products. Among essential nutrients/minerals, omega‐3‐fatty acids (O3FAs) have the strongest evidence of efficacy for bipolar depression, although some studies failed to find positive effects from O3FAs. Weak evidence supports efficacy of vitamin C whereas no data support the usefulness of folic acid and choline. Among nonessential nutrients, cytidine is the least supported treatment. Studies of N‐acetylcysteine have not resolved its efficacy in treating acute depressive episodes relative to placebo. However, one study demonstrates its potential to improve depressive symptoms over time and the other, though nonsignificant, suggests it has a prophylactic effect. Studies of inositol have been mostly negative, except for 1 study. Those that were negative were underpowered but demonstrated numerically positive effects for inositol. There is no evidence that citicholine is efficacious for uncomplicated BD depression, though it may have value for comorbid substance abuse among BD patients. Finally, combination O3FA‐cytidine lacks evidence of efficacy. The findings of this review do not support the routine use of nutritional supplements in the treatment or prophylaxis of BD depression. Studies with more rigorous designs are required before definitive conclusions can be made. Despite the inadequacy of the existing data, clinicians should remain open to the value of nutritional supplements: after all, lithium is a mineral too.     

Association of a Common Genetic Factor,PTGER3, With Outcome of Periodontal Therapy and Preterm Birth

Background: Clinical evidence suggests an association between preterm birth and periodontal disease. This study explores whether specific genetic polymorphisms are associated with success of periodontal therapy in pregnant women with periodontal disease and, further, whether any of these same polymorphisms are also associated with spontaneous preterm birth (sPTB). Methods: One hundred sixty high‐risk pregnant women (6 to 20 weeks of gestation) with periodontal disease (≥3 sites with attachment loss ≥4 mm) were studied. All women received scaling and root planing plus oral hygiene instruction. Periodontal examinations were performed before treatment and 20 weeks later. Participants were classified according to two study outcomes: 1) success or failure of periodontal treatment; and 2) presence or absence of sPTB. Maternal DNA samples from mucosal swabs were characterized using a 1536‐SNP (single‐nucleotide polymorphism) custom polymerase chain reaction chip. A probabilistic model of each dichotomous outcome, derived using a stepwise Bayesian procedure, was compared to respective null hypotheses on the basis of Monte Carlo simulations and significance estimates obtained using three measures (z‐test, Welch t‐test, and probability convolution). The models were further confirmed by logistic regression analyses. Results: The models revealed a significant relation between a specific polymorphism of prostaglandin E receptor 3 (a gene associated with inflammatory response) and both periodontal treatment failure (odds ratio 11.09, P <0.0002) and sPTB (odds ratio 6.89, P <0.0032). Conclusions: These results demonstrate that the risk of unsuccessful periodontal treatment is associated with tag SNPs in specific genes that regulate the inflammatory response, one of which is also associated with sPTB.