Homeostatic Proliferation Fails to Efficiently Reactivate HIV-1 Latently Infected Central Memory CD4+ T Cells

Homeostatic proliferation ensures the longevity of central memory T-cells by inducing cell proliferation in the absence of cellular differentiation or activation. This process is governed mainly by IL-7. Central memory T-cells can also be stimulated via engagement of the T-cell receptor, leading to cell proliferation but also activation and differentiation. Using an in vitro model of HIV-1 latency, we have examined in detail the effects of homeostatic proliferation on latently infected central memory T cells. We have also used antigenic stimulation via anti-CD3/anti-CD28 antibodies and established a comparison with a homeostatic proliferation stimulus, to evaluate potential differences in how either treatment affects the dynamics of latent virus populations. First, we show that homeostatic proliferation, as induced by a combination of IL-2 plus IL-7, leads to partial reactivation of latent HIV-1 but is unable to reduce the size of the reservoir in vitro. Second, latently infected cells are able to homeostatically proliferate in the absence of viral reactivation or cell differentiation. These results indicate that IL-2 plus IL-7 may induce a detrimental effect by favoring the maintenance of the latent HIV-1 reservoir. On the other hand, antigenic stimulation efficiently reactivated latent HIV-1 in cultured central memory cells and led to depletion of the latently infected cells via virus-induced cell death

Most bowel cancer symptoms do not indicate colorectal cancer and polyps: a systematic review

<p>Abstract</p> <p>Background</p> <p>Bowel symptoms are often considered an indication to perform colonoscopy to identify or rule out colorectal cancer or precancerous polyps. Investigation of bowel symptoms for this purpose is recommended by numerous clinical guidelines. However, the evidence for this practice is unclear. The objective of this study is to systematically review the evidence about the association between bowel symptoms and colorectal cancer or polyps.</p> <p>Methods</p> <p>We searched the literature extensively up to December 2008, using MEDLINE and EMBASE and following references. For inclusion in the review, papers from cross sectional, case control and cohort studies had to provide a 2×2 table of symptoms by diagnosis (colorectal cancer or polyps) or sufficient data from which that table could be constructed. The search procedure, quality appraisal, and data extraction was done twice, with disagreements resolved with another reviewer. Summary ROC analysis was used to assess the diagnostic performance of symptoms to detect colorectal cancer and polyps.</p> <p>Results</p> <p>Colorectal cancer was associated with rectal bleeding (AUC 0.66; LR+ 1.9; LR- 0.7) and weight loss (AUC 0.67, LR+ 2.5, LR- 0.9). Neither of these symptoms was associated with the presence of polyps. There was no significant association of colorectal cancer or polyps with change in bowel habit, constipation, diarrhoea or abdominal pain. Neither the clinical setting (primary or specialist care) nor study type was associated with accuracy.</p> <p>Most studies had methodological flaws. There was no consistency in the way symptoms were elicited or interpreted in the studies.</p> <p>Conclusions</p> <p>Current evidence suggests that the common practice of performing colonoscopies to identify cancers in people with bowel symptoms is warranted only for rectal bleeding and the general symptom of weight loss. Bodies preparing guidelines for clinicians and consumers to improve early detection of colorectal cancer need to take into account the limited value of symptoms.</p

First year clinical tutorials: students&rsquo; learning experience

Annette Burgess,1 Kim Oates,2 Kerry Goulston,2 Craig Mellis1 1Central Clinical School, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia; 2Sydney Medical School, The University of Sydney, Sydney, NSW, Australia Background: Bedside teaching lies at the heart of medical education. The learning environment afforded to students during clinical tutorials contributes substantially to their knowledge, thinking, and learning. Situated cognition theory posits that the depth and breadth of the students&#39; learning experience is dependent upon the attitude of the clinical teacher, the structure of the tutorial, and the understanding of tutorial and learning objectives. This theory provides a useful framework to conceptualize how students&#39; experience within their clinical tutorials impacts their knowledge, thinking, and learning. Methods: The study was conducted with one cohort (n=301) of students who had completed year 1 of the medical program at Sydney Medical School in 2013. All students were asked to complete a three-part questionnaire regarding their perceptions of their clinical tutor&#39;s attributes, the consistency of the tutor, and the best features of the tutorials and need for improvement. Both quantitative and qualitative data were collected and analyzed using descriptive statistics. Results: The response rate to the questionnaire was 88% (265/301). Students perceived that their tutors displayed good communication skills and enthusiasm, encouraged their learning, and were empathetic toward patients. Fifty-two percent of students reported having the same communications tutor for the entire year, and 28% reported having the same physical examination tutor for the entire year. Students would like increased patient contact, greater structure within their tutorials, and greater alignment of teaching with the curriculum. Conclusion: Situated cognition theory provides a valuable lens to view students&#39; experience of learning within the clinical environment. Our findings demonstrate students&#39; appreciation of clinical tutors as role models, the need for consistency in feedback, the importance of structure within tutorials, and the need for tutors to have an understanding of the curriculum and learning objectives for each teaching session. Keywords: bedside teaching, clinical tutorials, role modeling, situated cognitio

Reforming New South Wales public hospitals : an assessment of the Garling inquiry

* The final report of the Special Commission of Inquiry into Acute Care Services in NSW Public Hospitals was published on 27 November 2008. * The report acknowledges the challenges facing the New South Wales health system, including increasing numbers of patients, rising treatment costs, workforce pressures, and the breakdown of working relations between clinicians and management. * Many of Commissioner Garling's 139 recommendations formalise aspects of clinical care that should and could be happening now if the system were better managed, including better supervision and training of junior staff. * Commissioner Garling recommends that change should be driven by clinicians "from the bottom up, but does not adequately describe how this should happen. * Implementation of the report's recommendations that will require strong leadership and continuing consultation with clinicians and the community.2 page(s