Peer Observation and Evaluation Tool (POET): A Formative Peer Review Supporting Scholarly Teaching

The Peer Observation and Evaluation Tool (POET) is a valid and reliable measure developed for formative peer evaluation of pharmacy faculty. The authors replicated a study conducted on the POET in pharmacy in order to report the instrument’s validity and reliability in occupational therapy and to explore its potential as a formative teaching evaluation for occupational therapy educators. To verify item importance, seven participants from the faculty in an occupational therapy department rated each item. To establish inter-rater reliability, the participants evaluated one videotaped 55 min lecture. The POET was reliable with ICC at 0.93. There were high levels of agreement with the importance ratings among the participants with all scales. The POET appears to be a valid and reliable formative measure of teaching. At a time of significant change in the level of occupational therapy education, this measure may be an important support for scholarly teaching in two ways: First, this measure offers several opportunities to document the instructor’s strengths and, second, it offers the instructor suggestions about ways to improve teaching quality. Finally, the POET may facilitate faculty professional growth and development through systematic, strategic, and constructive peer review feedback

Using population attributable risk to choose HIV prevention strategies in men who have sex with men

<p>Abstract</p> <p>Background</p> <p>In Australia, HIV is concentrated in men who have sex with men (MSM) and rates have increased steadily over the past ten years. Health promotion strategies should ideally be informed by an understanding of both the prevalence of the factors being modified, as well as the size of the risk that they confer. We undertook an analysis of the potential population impact and cost saving that would likely result from modifying key HIV risk factors among men who have sex with men (MSM) in Sydney, Australia.</p> <p>Methods</p> <p>Proportional hazard analyses were used to examine the association between sexual behaviours in the last six months and sexually transmissible infections on HIV incidence in a cohort of 1426 HIV-negative MSM who were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. We then estimated the proportion of HIV infections that would be prevented if specific factors were no longer present in the population, using a population attributable risk (PAR) method which controls for confounding among factors. We also calculated the average lifetime healthcare costs incurred by the HIV infections associated with specific factors by estimating costs associated with clinical care and treatment following infection and discounting at 3% (1% and 5% sensitivity) to present value.</p> <p>Results</p> <p>Unprotected anal intercourse (UAI) with a known HIV-positive partner was reported by 5% of men, the hazard ratio (HR) was 16.1 (95%CI:6.4-40.5), the PAR was 34% (95%CI:24-44%) and the average lifetime HIV-related healthcare costs attributable to UAI with HIV-positive partners were $AUD102 million (uncertainty range:$93-114 m). UAI with unknown HIV status partners was reported by 25% of men, the HR was 4.4 (95%CI:1.8-11.2), the PAR was 33% (95%CI:26-42%) and the lifetime incurred costs were $AUD99 million. Anal warts prevalence was 4$AUD39 million.</p> <p>Conclusions</p> <p>Our analysis has found that although UAI with an HIV-positive sexual partner is a relatively low-prevalence behaviour (reported by 5% of men), if this behaviour was not present in the population, the number of infections would be reduced by one third. No other single behaviour or sexually transmissible infections contributes to a greater proportion of infections and HIV-related healthcare costs.</p

Sca-1+ cardiac fibroblasts promote development of heart failure

The causative effect of GM-CSF produced by cardiac fibroblasts to development of heart failure has not been shown. We identified the pathological GM-CSF-producing cardiac fibroblast subset and the specific deletion of IL-17A signaling to these cells attenuated cardiac inflammation and heart failure. We describe here the CD45−CD31−CD29+mEFSK4+PDGFRα+Sca-1+periostin+ (Sca-1+) cardiac fibroblast subset as the main GM-CSF producer in both experimental autoimmune myocarditis and myocardial infarction mouse models. Specific ablation of IL-17A signaling to Sca-1+periostin+ cardiac fibroblasts (PostnCreIl17rafl/fl) protected mice from post-infarct heart failure and death. Moreover, PostnCreIl17rafl/fl mice had significantly fewer GM-CSF-producing Sca-1+ cardiac fibrob-lasts and inflammatory Ly6Chi monocytes in the heart. Sca-1+ cardiac fibroblasts were not only potent GM-CSF producers, but also exhibited plasticity and switched their cytokine production profiles depending on local microenvironments. Moreover, we also found GMCSF-positive cardiac fibroblasts in cardiac biopsy samples from heart failure patients of myocarditis or ischemic origin. Thus, this is the first identification of a pathological GMCSF-producing cardiac fibroblast subset in human and mice hearts with myocarditis and ischemic cardiomyopathy. Sca-1+ cardiac fibroblasts direct the type of immune cells infiltrating the heart during cardiac inflammation and drive the development of heart failure

NF-κB activity marks cells engaged in receptor editing

Because of the extreme diversity in immunoglobulin genes, tolerance mechanisms are necessary to ensure that B cells do not respond to self-antigens. One such tolerance mechanism is called receptor editing. If the B cell receptor (BCR) on an immature B cell recognizes self-antigen, it is down-regulated from the cell surface, and light chain gene rearrangement continues in an attempt to edit the autoreactive specificity. Analysis of a heterozygous mutant mouse in which the NF-κB–dependent IκBα gene was replaced with a lacZ (β-gal) reporter complementary DNA (cDNA; IκBα+/lacZ) suggests a potential role for NF-κB in receptor editing. Sorted β-gal+ pre–B cells showed increased levels of various markers of receptor editing. In IκBα+/lacZ reporter mice expressing either innocuous or self-specific knocked in BCRs, β-gal was preferentially expressed in pre–B cells from the mice with self-specific BCRs. Retroviral-mediated expression of a cDNA encoding an IκBα superrepressor in primary bone marrow cultures resulted in diminished germline κ and rearranged λ transcripts but similar levels of RAG expression as compared with controls. We found that IRF4 transcripts were up-regulated in β-gal+ pre–B cells. Because IRF4 is a target of NF-κB and is required for receptor editing, we suggest that NF-κB could be acting through IRF4 to regulate receptor editing

Bacterial Effector Binding to Ribosomal Protein S3 Subverts NF-κB Function

Enteric bacterial pathogens cause food borne disease, which constitutes an enormous economic and health burden. Enterohemorrhagic Escherichia coli (EHEC) causes a severe bloody diarrhea following transmission to humans through various means, including contaminated beef and vegetable products, water, or through contact with animals. EHEC also causes a potentially fatal kidney disease (hemolytic uremic syndrome) for which there is no effective treatment or prophylaxis. EHEC and other enteric pathogens (e.g., enteropathogenic E. coli (EPEC), Salmonella, Shigella, Yersinia) utilize a type III secretion system (T3SS) to inject virulence proteins (effectors) into host cells. While it is known that T3SS effectors subvert host cell function to promote diarrheal disease and bacterial transmission, in many cases, the mechanisms by which these effectors bind to host proteins and disrupt the normal function of intestinal epithelial cells have not been completely characterized. In this study, we present evidence that the E. coli O157:H7 nleH1 and nleH2 genes encode T3SS effectors that bind to the human ribosomal protein S3 (RPS3), a subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcriptional complexes. NleH1 and NleH2 co-localized with RPS3 in the cytoplasm, but not in cell nuclei. The N-terminal region of both NleH1 and NleH2 was required for binding to the N-terminus of RPS3. NleH1 and NleH2 are autophosphorylated Ser/Thr protein kinases, but their binding to RPS3 is independent of kinase activity. NleH1, but not NleH2, reduced the nuclear abundance of RPS3 without altering the p50 or p65 NF-κB subunits or affecting the phosphorylation state or abundance of the inhibitory NF-κB chaperone IκBα NleH1 repressed the transcription of a RPS3/NF-κB-dependent reporter plasmid, but did not inhibit the transcription of RPS3-independent reporters. In contrast, NleH2 stimulated RPS3-dependent transcription, as well as an AP-1-dependent reporter. We identified a region of NleH1 (N40-K45) that is at least partially responsible for the inhibitory activity of NleH1 toward RPS3. Deleting nleH1 from E. coli O157:H7 produced a hypervirulent phenotype in a gnotobiotic piglet model of Shiga toxin-producing E. coli infection. We suggest that NleH may disrupt host innate immune responses by binding to a cofactor of host transcriptional complexes

Specification of DNA Binding Activity of NF-κB Proteins

Nuclear factor-κB (NF-κB) is a pleiotropic mediator of inducible and specific gene regulation involving diverse biological activities including immune response, inflammation, cell proliferation, and death. The fine-tuning of the NF-κB DNA binding activity is essential for its fundamental function as a transcription factor. An increasing body of literature illustrates that this process can be elegantly and specifically controlled at multiple levels by different protein subsets. In particular, the recent identification of a non-Rel subunit of NF-κB itself provides a new way to understand the selective high-affinity DNA binding specificity of NF-κB conferred by a synergistic interaction within the whole complex. Here, we review the mechanism of the specification of DNA binding activity of NF-κB complexes, one of the most important aspects of NF-κB transcriptional control

HIV Testing and HIV Serostatus-Specific Sexual Risk Behaviour Among Men Who Have Sex with Men Living in England and Recruited Through the Internet in 2001 and 2008.

Using data from two large internet-recruited surveys in England in 2001 and 2008, we examine HIV status-specific patterns of unprotected anal intercourse (UAI). In adjusted comparisons between our 2008 and 2001 samples, there was evidence of a greater proportion of men living with diagnosed HIV, a reduction in sexual partners and in UAI with partners of unknown HIV status among men not tested HIV positive, increases in anal intercourse and UAI among men with diagnosed HIV and an increase in insertive UAI with HIV-positive men among men never tested for HIV. However, we found no evidence for increases in negotiated safety or sero-sorting. The data are compatible with a concentration of sexual risk among men with diagnosed HIV, countering an overall trend towards less risk taking among men not tested HIV positive

Protein Kinase A Phosphorylation Activates Vpr-Induced Cell Cycle Arrest during Human Immunodeficiency Virus Type 1 Infection▿

Infection with human immunodeficiency virus type 1 (HIV-1) causes an inexorable depletion of CD4+ T cells. The loss of these cells is particularly pronounced in the mucosal immune system during acute infection, and the data suggest that direct viral cytopathicity is a major factor. Cell cycle arrest caused by the HIV-1 accessory protein Vpr is strongly correlated with virus-induced cell death, and phosphorylation of Vpr serine 79 (S79) is required to activate G2/M cell cycle blockade. However, the kinase responsible for phosphorylating Vpr remains unknown. Our bioinformatic analyses revealed that S79 is part of a putative phosphorylation site recognized by protein kinase A (PKA). We show here that PKA interacts with Vpr and directly phosphorylates S79. Inhibition of PKA activity during HIV-1 infection abrogates Vpr cell cycle arrest. These findings provide new insight into the signaling event that activates Vpr cell cycle arrest, ultimately leading to the death of infected T cells