Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges.

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route.Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines.Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy

The role of reinvestment in conservative gait in older adults

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordPrevious research suggests that reinvestment (i.e. conscious control of movements) is associated with inefficient information processing and compromised movement strategies in older adults during walking. We examined whether reinvestment propensity is associated with conservative gait behaviour in older adults. Trait Reinvestment propensity was measured using the Movement Specific Reinvestment Scale (Chinese version) (MSRS-C). Thirty-eight older adults were categorized into ‘Low Reinvestor Group’ (LRG) (MSRS-C 38). There were no significant differences in physical and cognitive abilities between groups. Participants were asked to walk along a 6-m straight level-ground walkway at a self-selected pace under conditions of no instruction (Baseline), instruction related to self-focus on body movements (BI), and instruction related to the external environment (EI). No significant difference was found in gait behaviour between LRG and HRG at Baseline. However, significant changes, indicative of conservative gait patterns, were found in LRG when given instructions that prompted them to consciously control their body movements. No changes were observed in HRG under external-related instructions that are assumed to reduce conscious motor processing and improve motor performance. Our findings contradict previous views on the association between trait reinvestment propensity and compromised motor performance in older adults, which potentially reduces justification for reducing trait reinvestment propensity in older adults. We also suggest that MSRS is insensitive to reflect the degree of conscious control during gait tasks. Our findings also implicate the potential detrimental effect of applying inward-focus-related instructions in healthcare rehabilitation settings.Research Grants Council of the Hong Kong Special Administrative Region, Chin

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)

Quantitative evaluation of recall and precision of CAT Crawler, a search engine specialized on retrieval of Critically Appraised Topics

BACKGROUND: Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository. METHODS: A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated. RESULTS: While achieving an identical recall, the meta-search engine showed a precision of 77.26% (±14.45) compared to the individual search engines' 52.65% (±12.0) (p < 0.001). CONCLUSION: The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians

Sociodemographic Trends in National Ambulatory Care Visits for Hepatitis C Virus Infection

Poor and non-white patients are disproportionately infected with the hepatitis C virus (HCV). The objective of this research is to determine sociodemographic patterns of HCV-related ambulatory care visits over time. Data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey-Outpatient (NHAMCS-OPD) for the years 1997–2005 were analyzed in 3-year intervals. Demographic and other variables were compared for each period, and multivariable logistic regression was performed to examine whether the likelihood of a visit being HCV-related (versus non-HCV) was independently associated with (1) race and/or (2) Medicaid status over time. The total number of HCV-related ambulatory visits more than doubled from 3,583,585 during the years 1997–1999 to 8,027,166 during 2003–2005. During this time, the proportion of non-whites and Medicaid recipients presenting for HCV-related visits approximately doubled (non-whites: 16% vs. 33%, P = 0.04; Medicaid recipients: 10% vs. 25%, P = 0.07). In 2003–2005, HCV-related visits were more than twice as likely to occur among non-white patients vs. white patients (OR = 2.49; 95% CI: 1.60–3.86) and patients on Medicaid vs. non-Medicaid (3.49; 1.79–6.80). Our results show that HCV-associated ambulatory care visits are increasing, with a greater proportion of visits occurring among non-white patients and Medicaid recipients

Emergent dynamic chirality in a thermally driven artificial spin ratchet

Modern nanofabrication techniques have opened the possibility to create novel functional materials, whose properties transcend those of their constituent elements. In particular, tuning the magnetostatic interactions in geometrically frustrated arrangements of nanoelements called artificial spin ice1, 2 can lead to specific collective behaviour3, including emergent magnetic monopoles4, 5, charge screening6, 7 and transport8, 9, as well as magnonic response10, 11, 12. Here, we demonstrate a spin-ice-based active material in which energy is converted into unidirectional dynamics. Using X-ray photoemission electron microscopy we show that the collective rotation of the average magnetization proceeds in a unique sense during thermal relaxation. Our simulations demonstrate that this emergent chiral behaviour is driven by the topology of the magnetostatic field at the edges of the nanomagnet array, resulting in an asymmetric energy landscape. In addition, a bias field can be used to modify the sense of rotation of the average magnetization. This opens the possibility of implementing a magnetic Brownian ratchet13, 14, which may find applications in novel nanoscale devices, such as magnetic nanomotors, actuators, sensors or memory cells

Multi-Family Psycho-Education Group for Assertive Community Treatment Clients and Families of Culturally Diverse Background: A Pilot Study

This study evaluates the incorporation of Multi-Family Psycho-education Group (MFPG) to an Assertive Community Treatment Team developed to serve culturally diverse clients who suffers from severe mental illness. Participants included Chinese and Tamil clients and their family members. Family members’ well-being, perceived burden, and acceptance of clients were assessed before and after the intervention. Focus group interviews with clinicians were conducted to qualitatively examine MFPG. Family members’ acceptance increased after MFPG. Regular attendance was associated with reduction in perceived family burden. Culturally competent delivery of MFPG enhanced family members’ understanding of mental illness and reduced stress levels and negative feelings towards clients

Search algorithms as a framework for the optimization of drug combinations

Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms, originally developed for digital communication, modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs with only one third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6-9 interventions in 80-90% of tests, compared with 15-30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution.Comment: 36 pages, 10 figures, revised versio