Predictors of health decline in older adults with pneumonia: findings from the Community Acquired Pneumonia Impact Study

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify predictors of health decline among older adults with clinically diagnosed community acquired pneumonia (CAP). It was hypothesized that older adults with CAP who had lower levels of social support would be more likely to report a decline in health.</p> <p>Methods</p> <p>A telephone survey was used to collect detailed information from older adults about their experiences with CAP. A broader determinants of health framework was used to guide data collection. This was a community wide study with participants being recruited from all radiology clinics in one Ontario community.</p> <p>Results</p> <p>The most important predictors of a health decline included: two symptoms (no energy; diaphoresis), two lifestyle variables (being very active; allowing people to smoke in their home), one quality of life variable (little difficulty in doing usual daily activities) and one social support variable (having siblings).</p> <p>Conclusions</p> <p>A multiplicity of factors was found to be associated with a decline in health among older adults with clinically diagnosed CAP. These findings may be useful to physicians, family caregivers and others for screening older adults and providing interventions to help ensure positive health outcomes.</p

CD4(+)CD25(+)FOXP3(+) Regulatory T Cells Suppress Anti-Tumor Immune Responses in Patients with Colorectal Cancer

BACKGROUND: A wealth of evidence obtained using mouse models indicates that CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) maintain peripheral tolerance to self-antigens and also inhibit anti-tumor immune responses. To date there is limited information about CD4(+) T cell responses in patients with colorectal cancer (CRC). We set out to measure T cell responses to a tumor-associated antigen and examine whether Treg impinge on those anti-tumor immune responses in CRC patients. METHODOLOGY AND PRINCIPAL FINDINGS: Treg were identified and characterized as CD4(+)CD25(+)FOXP3(+) using flow cytometry. An increased frequency of Treg was demonstrated in both peripheral blood and mesenteric lymph nodes of patients with colorectal cancer (CRC) compared with either healthy controls or patients with inflammatory bowel disease (IBD). Depletion of Treg from peripheral blood mononuclear cells (PBMC) of CRC patients unmasked CD4(+) T cell responses, as observed by IFNγ release, to the tumor associated antigen 5T4, whereas no effect was observed in a healthy age-matched control group. CONCLUSIONS/SIGNIFICANCE: Collectively, these data demonstrate that Treg capable of inhibiting tumor associated antigen-specific immune responses are enriched in patients with CRC. These results support a rationale for manipulating Treg to enhance cancer immunotherapy

A multidisciplinary cognitive behavioural programme for coping with chronic neuropathic pain following spinal cord injury: the protocol of the CONECSI trial

<p>Abstract</p> <p>Background</p> <p>Most people with a spinal cord injury rate neuropathic pain as one of the most difficult problems to manage and there are no medical treatments that provide satisfactory pain relief in most people. Furthermore, psychosocial factors have been considered in the maintenance and aggravation of neuropathic spinal cord injury pain. Psychological interventions to support people with spinal cord injury to deal with neuropathic pain, however, are sparse. The primary aim of the CONECSI (COping with NEuropathiC Spinal cord Injury pain) trial is to evaluate the effects of a multidisciplinary cognitive behavioural treatment programme on pain intensity and pain-related disability, and secondary on mood, participation in activities, and life satisfaction.</p> <p>Methods/Design</p> <p>CONECSI is a multicentre randomised controlled trial. A sample of 60 persons with chronic neuropathic spinal cord injury pain will be recruited from four rehabilitation centres and randomised to an intervention group or a waiting list control group. The control group will be invited for the programme six months after the intervention group. Main inclusion criteria are: having chronic (> 6 months) neuropathic spinal cord injury pain as the worst pain complaint and rating the pain intensity in the last week as 40 or more on a 0-100 scale. The intervention consists of educational, cognitive, and behavioural elements and encompasses 11 sessions over a 3-month period. Each meeting will be supervised by a local psychologist and physical therapist. Measurements will be perfomed before starting the programme/entering the control group, and at 3, 6, 9, and 12 months. Primary outcomes are pain intensity and pain-related disability (Chronic Pain Grade questionnaire). Secondary outcomes are mood (Hospital Anxiety and Depression Scale), participation in activities (Utrecht Activities List), and life satisfaction (Life Satisfaction Questionnaire). Pain coping and pain cognitions will be assessed with three questionnaires (Coping Strategy Questionnaire, Pain Coping Inventory, and Pain Cognition List).</p> <p>Discussion</p> <p>The CONECSI trial will reveal the effects of a multidisciplinary cognitive behavioural programme for people with chronic neuropathic spinal cord injury pain. This intervention is expected to contribute to the rehabilitation treatment possibilities for this population.</p> <p>Trial Registration</p> <p>Dutch Trial Register NTR1580.</p

CXCR4 Mediated Chemotaxis Is Regulated by 5T4 Oncofetal Glycoprotein in Mouse Embryonic Cells

5T4 oncofetal molecules are highly expressed during development and upregulated in cancer while showing only low levels in some adult tissues. Upregulation of 5T4 expression is a marker of loss of pluripotency in the early differentiation of embryonic stem (ES) cells and forms an integrated component of an epithelial-mesenchymal transition, a process important during embryonic development and metastatic spread of epithelial tumors. Investigation of the transcriptional changes in early ES differentiation showed upregulation of CXCL12 and down-regulation of a cell surface protease, CD26, which cleaves this chemokine. CXCL12 binds to the widely expressed CXCR4 and regulates key aspects of development, stem cell motility and tumour metastasis to tissues with high levels of CXCL12. We show that the 5T4 glycoprotein is required for optimal functional cell surface expression of the chemokine receptor CXCR4 and CXCL12 mediated chemotaxis in differentiating murine embryonic stem cells and embryo fibroblasts (MEF). Cell surface expression of 5T4 and CXCR4 molecules is co-localized in differentiating ES cells and MEF. By contrast, differentiating ES and MEF derived from 5T4 knockout (KO) mice show only intracellular CXCR4 expression but infection with adenovirus encoding mouse 5T4 restores CXCL12 chemotaxis and surface co-localization with 5T4 molecules. A series of chimeric constructs with interchanged domains of 5T4 and the glycoprotein CD44 were used to map the 5T4 sequences relevant for CXCR4 membrane expression and function in 5T4KO MEF. These data identified the 5T4 transmembrane domain as sufficient and necessary to enable CXCR4 cell surface expression and chemotaxis. Furthermore, some monoclonal antibodies against m5T4 can inhibit CXCL12 chemotaxis of differentiating ES cells and MEF which is not mediated by simple antigenic modulation. Collectively, these data support a molecular interaction of 5T4 and CXCR4 occurring at the cell surface which directly facilitates the biological response to CXCL12. The regulation of CXCR4 surface expression by 5T4 molecules is a novel means to control responses to the chemokine CXCL12 for example during embryogenesis but can also be selected to advantage the spread of a 5T4 positive tumor from its primary site

Comparing perception-based and geographic information systems (GIS) based characterizations of the local food environment

Measuring features of the local food environment has been a major challenge in studying the effect of the environment on diet. This study examined associations between alternate ways of characterizing the local food environment by comparing Geographic Information System (GIS)-derived densities of various types of stores to perception-based measures of the availability of healthy foods. Survey questions rating the availability of produce and low-fat products in neighborhoods were aggregated into a healthy food availability score for 5,774 residents of North Carolina, Maryland, and New York. Densities of supermarkets and smaller stores per square mile were computed for 1 mile around each respondent’s residence using kernel estimation. The number of different store types in the area was used to measure variety in the food environment. Linear regression was used to examine associations of store densities and variety with reported availability. Respondents living in areas with lower densities of supermarkets rated the selection and availability of produce and low-fat foods 17% lower than those in areas with the highest densities of supermarkets (95% CL, −18.8, −15.1). In areas without supermarkets, low densities of smaller stores and less store variety were associated with worse perceived availability of healthy foods only in North Carolina (8.8% lower availability, 95% CL, −13.8, −3.4 for lowest vs. highest small-store density; 10.5% lower 95% CL, −16.0, −4.7 for least vs. most store variety). In contrast, higher smaller store densities and more variety were associated with worse perceived healthy food availability in Maryland. Perception- and GIS-based characterizations of the environment are associated but are not identical. Combinations of different types of measures may yield more valid measures of the environment.http://deepblue.lib.umich.edu/bitstream/2027.42/58001/1/Comparing perception based and geographic informatin systems GIS based characterizations of the local food environment.pd

Potential therapeutic applications of microbial surface-activecompounds

Numerous investigations of microbial surface-active compounds or biosurfactants over the past two decades have led to the discovery of many interesting physicochemical and biological properties including antimicrobial, anti-biofilm and therapeutic among many other pharmaceutical and medical applications. Microbial control and inhibition strategies involving the use of antibiotics are becoming continually challenged due to the emergence of resistant strains mostly embedded within biofilm formations that are difficult to eradicate. Different aspects of antimicrobial and anti-biofilm control are becoming issues of increasing importance in clinical, hygiene, therapeutic and other applications. Biosurfactants research has resulted in increasing interest into their ability to inhibit microbial activity and disperse microbial biofilms in addition to being mostly nontoxic and stable at extremes conditions. Some biosurfactants are now in use in clinical, food and environmental fields, whilst others remain under investigation and development. The dispersal properties of biosurfactants have been shown to rival that of conventional inhibitory agents against bacterial, fungal and yeast biofilms as well as viral membrane structures. This presents them as potential candidates for future uses in new generations of antimicrobial agents or as adjuvants to other antibiotics and use as preservatives for microbial suppression and eradication strategies