Computerized cognitive training with older adults: a systematic review

A systematic review to examine the efficacy of computer-based cognitive interventions for cognitively healthy older adults was conducted. Studies were included if they met the following criteria: average sample age of at least 55 years at time of training; participants did not have Alzheimer's disease or mild cognitive impairment; and the study measured cognitive outcomes as a result of training. Theoretical articles, review articles, and book chapters that did not include original data were excluded. We identified 151 studies published between 1984 and 2011, of which 38 met inclusion criteria and were further classified into three groups by the type of computerized program used: classic cognitive training tasks, neuropsychological software, and video games. Reported pre-post training effect sizes for intervention groups ranged from 0.06 to 6.32 for classic cognitive training interventions, 0.19 to 7.14 for neuropsychological software interventions, and 0.09 to 1.70 for video game interventions. Most studies reported older adults did not need to be technologically savvy in order to successfully complete or benefit from training. Overall, findings are comparable or better than those from reviews of more traditional, paper-and-pencil cognitive training approaches suggesting that computerized training is an effective, less labor intensive alternative.     

Identification of Pseudomonas aeruginosa genes required for epithelial cell injury

We have developed a simple, reproducible and rapid genetic screen for Pseudomonas aeruginosa -induced epithelial cell cytotoxicity in cultures of MDCK cells. This screen was used to isolate isogenic transposon-tagged non-cytotoxic mutants of a cytotoxic and lung-virulent strain of P. aeruginosa (PA103). The transposon-insertion site was determined by using an inverse polymerase chain reaction followed by DNA-sequence analysis. On the basis of phenotype and sequence analysis, these mutants fell into four classes. One class had absent or defective pili, based on their resistance to phage PO4 and/or loss of twitching motility (twt⁻). A second class exhibited decreased adherence. A third class of mutants exhibited probable defects in the machinery or targets of type III protein secretion. A final class of mutants exhibited decreased but not absent cytotoxicity. This class included members of the first three classes as well as other mutants. These results suggest that localized cytotoxicity is likely to require several steps and several components, including pili and other (unidentified) extracellular proteins. The type III protein-secretion apparatus appears to be involved in this process.     

A genetic study of two French Guiana Amerindian populations

Summary Phenotypes and gene frequencies are presented for 20 serum and erythrocyte proteins in two Amerindian populations of inner French Guiana. No genetic variability was detected in 12 of these systems. Heterozygosity was calculated for the others and the reasons for its variation are discussed.     

RECENT RADIATION OF THE PALMARIACEAE (RHODOPHYTA)1

Molecular phylogenetic studies on the evolution of the red algae indicate that this ancient division has many lineages that have recently undergone radiations. One such example is the cold–temperate family Palmariaceae. In this study, sequences from the ribosomal DNA internal transcribed spacer regions were compared among ten species in the Palmariaceae from both Atlantic and Pacific sites, Phylogenetic analyses of sequence data, in which Rhodophysema georgii Batters was used as outgroup and root, indicate a radiation into four clades, three of which contain species of “Palmaria” and the fourth species of Halosaccion. Palmaria palmata (L.) Kuntze, the type and only North Atlantic species in the genus, stands apart from all remaining species in the family and terminates the most basal branch in the rooted tree. The three more derived clades have radiated mainly in the North Pacific. Southern Ocean Palmaria and North Atlantic Devaleraea are hypothesized to have invaded from separate but closely related North Pacific ancestors. The ease with which sequences could be aligned combined with an unsaturated transition: transversion ratio and modest divergence involving predominantly point mutations suggests that the initial radiation is relatively recent (late Miocene–Pliocene) and that the Devaleraea–Palmaria clade is even more recent (late Pliocene–Pleistocene).     

Eosinophil and T cell markers predict functional decline in COPD patients

Background

The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.

Methods

Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.

Results and Discussion

Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).

Conclusion

These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.     

Cellular Immune Responses to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) Infection in Senescent BALB/c Mice: CD4+ T Cells Are Important in Control of SARS-CoV Infection

We characterized the cellular immune response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection in 12- to 14-month-old BALB/c mice, a model that mimics features of the human disease. Following intranasal administration, the virus replicated in the lungs, with peak titers on day 2 postinfection. Enhanced production of cytokines (tumor necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) and chemokines (CXCL10, CCL2, CCL3, and CCL5) correlated with migration of NK cells, macrophages, and plasmacytoid dendritic cells (pDC) into the lungs. By day 7, histopathologic evidence of pneumonitis was seen in the lungs when viral clearance occurred. At this time, a second wave of enhanced production of cytokines (TNF-α, IL-6, gamma interferon [IFN-γ], IL-2, and IL-5), chemokines (CXCL9, CXCL10, CCL2, CCL3, and CCL5), and receptors (CXCR3, CCR2, and CCR5), was detected in the lungs, associated with an influx of T lymphocytes. Depletion of CD8⁺ T cells at the time of infection did not affect viral replication or clearance. However, depletion of CD4⁺ T cells resulted in an enhanced immune-mediated interstitial pneumonitis and delayed clearance of SARS-CoV from the lungs, which was associated with reduced neutralizing antibody and cytokine production and reduced pulmonary recruitment of lymphocytes. Innate defense mechanisms are able to control SARS-CoV infection in the absence of CD4⁺ and CD8⁺ T cells and antibodies. Our findings provide new insights into the pathogenesis of SARS, demonstrating the important role of CD4⁺ but not CD8⁺ T cells in primary SARS-CoV infection in this model.The global outbreak of severe acute respiratory syndrome (SARS) in 2003 that infected more than 8,000 people in 29 countries across five continents, with 774 deaths reported by the World Health Organization (54), was caused by a highly contagious coronavirus designated SARS-CoV (33). The elderly were more likely to die from SARS-CoV infection than younger people (7), with a case-fatality rate of 50% in people older than 65 years (14, 53). Disease pathogenesis in SARS is complex, with multiple factors leading to severe pulmonary injury and dissemination of the virus to other organs. High viral load; systemic infection; a cytokine storm with high levels of CXCL10/IP-10, CCL3/MIP-1α, and CCL2/MCP-1; massive lung infiltration by monocytes and macrophages; and rapid depletion of T cells are hallmarks of SARS (5, 13, 15, 21, 28, 35). The role of neutralizing antibodies (Abs) in protection from SARS-CoV infection has been well documented. Virus-specific neutralizing Abs reduce viral load, protect against weight loss, and reduce histopathology in animal models (42, 47, 48). Although the role of type I interferons (IFNs) in the natural history of SARS is controversial (5, 9, 59), the innate defense system appears to be critical for controlling SARS-CoV replication in mice (23, 41). Mice lacking normal innate signaling due to STAT1 or MyD88 deficiency are highly susceptible to SARS-CoV infection. Virus-specific T-cell responses are present in convalescent patients with SARS (27, 55). However, little is known about the role of T cells in the acute phase of SARS.Several mouse models have been developed for the in vivo study of SARS pathogenesis. However, no single model accurately reproduces all aspects of the human disease. SARS-CoV replicates in the upper and lower respiratory tracts of 4- to 8-week-old mice and is cleared rapidly; infection is associated with transient mild pneumonitis, and cytokines are not detectable in the lungs (20, 42, 49). A SARS-CoV isolate that was adapted by serial passage in mice (MA-15) replicates to a higher titer and for a longer duration in the lungs than the unadapted (Urbani) virus and is associated with viremia and mortality in young mice (36), but the histologic changes in the lungs are caused by high titers of virus and cell death without significant infiltrates of inflammatory cells. The heightened susceptibility of elderly patients to SARS led us to develop a pneumonia model in 12- to 14-month-old (mo) BALB/c mice using the Urbani virus. In this model, pulmonary replication of virus was associated with signs of clinical illness and histopathological evidence of disease characterized by bronchiolitis, interstitial pneumonitis, diffuse alveolar damage, and fibrotic scarring (3), thus resembling SARS in the elderly. We evaluated the host response to SARS-CoV infection by examining the gene expression profile in the senescent mouse model and found a robust response to virus infection, with an increased expression of several immune response and cell-to-cell signaling genes, including those for tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), CCL2, CCL3, CXCL10, and IFN-γ (1).In this study, we characterize the cellular immune response to SARS-CoV infection in 12- to 14-mo BALB/c mice in terms of the protein and gene expression of inflammatory mediators, migration of inflammatory cells, and virus-specific T-cell responses in the lungs during the course of disease. We evaluated the role of T cells in disease pathogenesis and viral clearance by depleting T-cell subsets at the time of infection and found an important role for CD4⁺ T cells (but not CD8⁺ T cells) in primary infection with SARS-CoV in this model.