Blastomyces dermatitidis yeast cells inhibit nitric oxide production by alveolar macrophage inducible nitric oxide synthase.

The ability of pathogens to evade host antimicrobial mechanisms is crucial to their virulence. The dimorphic fungal pathogen Blastomyces dermatitidis can infect immunocompetent patients, producing a primary pulmonary infection that can later disseminate to other organs. B. dermatitidis possesses a remarkable ability to resist killing by alveolar macrophages. To date, no mechanism to explain this resistance has been described. Here, we focus on macrophage production of the toxic molecule nitric oxide as a potential target of subversion by B. dermatitidis yeast cells. We report that B. dermatitidis yeast cells reduce nitric oxide levels in the supernatants of activated alveolar macrophages. This reduction is not due to detoxification of nitric oxide, but rather to suppression of macrophage nitric oxide production. We show that B. dermatitidis yeast cells do not block upregulation of macrophage inducible nitric oxide synthase (iNOS) expression or limit iNOS access to its arginine substrate. Instead, B. dermatitidis yeast cells appear to inhibit iNOS enzymatic activity. Further investigation into the genetic basis of this potential virulence mechanism could lead to the identification of novel antifungal drug targets.

Lights! Camera! Action!: video projects in the classroom.

We report on two classroom video projects intended to promote active student involvement in their classroom experience during a year-long medical-surgical nursing course. We implemented two types of projects, Nursing Grand Rounds and FPBTV. The projects are templates that can be applied to any nursing specialty and can be implemented without the use of video technology. During the course of several years, both projects have proven effective in encouraging students to promote pattern recognition of characteristic features of common illnesses, to develop teamwork strategies, and to practice their presentation skills in a safe environment among their peers. The projects appealed to students because they increased retention of information and immersed students in the experience of becoming experts about an illness or a family of medications. These projects have enabled students to become engaged and invested in their own learning in the classroom.

Symptomatic ileofemoral deep vein thrombosis due to May-Thurner syndrome.

A 33-year-old woman with no medical history reported an acute onset of left leg and thigh swelling. A review of her medications revealed that she had started oral contraceptives 2 months previously. Ultrasonography and subsequent venography demonstrated extensive ileofemoral clot burden. Thrombolysis and thrombectomy successfully restored venous return with subsequent improvement in the leg swelling and oedema. In this case, we describe a patient presenting with extensive ileofemoral deep vein thrombosis, otherwise known as the May-Thurner syndrome.

Patient-centered plan-of-care tool for improving clinical outcomes.

PURPOSE: In developing our Patient-Centered Team Care (PCTC) program, we designed a Plan-of-Care (POC) tool to facilitate the physician-patient discussion for setting health goals. This study aimed to determine the effectiveness of the POC tool in improving clinical outcomes. METHODS: We compared baseline and 6-month or greater follow-up values for hemoglobin A1c (HbA1c), low-density lipoprotein (LDL), systolic blood pressure (SP), diastolic blood pressure (DP), and weight for PCTC patients (intervention group) and non-PCTC patients (control group). For the intervention group, we also compared POC tool completeness scores (1, low and 8, high). RESULTS: Of 1366 patients, 1110 (593 intervention, 517 control) had baseline and follow-up clinical measures for analysis. After adjusting for demographics, significant effects occurred in the intervention group for HbA1c (P = .0067), LDL (P = .012), and DP (P = .091). For completeness of POC, a significant association occurred between more fully completed forms (scores, 5-8) and change in HbA1c (P < .001) and SP (P = .011). CONCLUSION: Patients receiving a POC showed significant improvement in 3 of 5 clinical outcomes compared with those without the tool, and those with more fully completed forms had significant improvement in 2 of 5 clinical outcomes compared with those with partially completed forms.

Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice.

Worldwide rates of systemic fungal infections, including three of the major pathogens responsible for such infections in North America (Coccidioides posadasii, Histoplasma capsulatum, and Blastomyces dermatitidis), have soared recently, spurring interest in developing vaccines. The development of Th1 cells is believed to be crucial for protective immunity against pathogenic fungi, whereas the role of Th17 cells is vigorously debated. In models of primary fungal infection, some studies have shown that Th17 cells mediate resistance, while others have shown that they promote disease pathology. Here, we have shown that Th1 immunity is dispensable and that fungus-specific Th17 cells are sufficient for vaccine-induced protection against lethal pulmonary infection with B. dermatitidis in mice. Further, vaccine-induced Th17 cells were necessary and sufficient to protect against the three major systemic mycoses in North America. Mechanistically, Th17 cells engendered protection by recruiting and activating neutrophils and macrophages to the alveolar space, while the induction of Th17 cells and acquisition of vaccine immunity unexpectedly required the adapter molecule Myd88 but not the fungal pathogen recognition receptor Dectin-1. These data suggest that human vaccines against systemic fungal infections should be designed to induce Th17 cells if they are to be effective.

Randomized trial of web-based training about opioid therapy for chronic pain.

OBJECTIVES: The treatment of chronic noncancer pain with chronic opioid therapy has increased rapidly, but medicine residents receive little training concerning this therapy. Therefore we conducted a trial to determine if an interactive web-based training focusing on shared decision-making for chronic opioid therapy improves knowledge and competence compared with exposure to practice guidelines. METHODS: A randomized controlled educational trial of 213 internal medicine residents from 5 medicine residencies participating in the Residency Review Committee for Internal Medicine's Educational Innovations Project comparing access to interactive web-based training (COPE: Collaborative Opioid Prescribing Education) or access to the Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of Opioid Therapy for Chronic Pain. Pretraining and immediate posttraining knowledge test; pretraining and 60-day posttraining self-reported competence, satisfaction, patient-centeredness, and selected clinical behaviors were analyzed using t tests, Pearson chi, and Generalized Estimating Equations. RESULTS: The web training group had greater increase in knowledge with training (chi(2)=72.06, P<0.00001) and greater self-rated competence in the management of outpatients with chronic pain (chi(2)=6.48, P=0.01), and specifically in the use of opioids in this management (chi(2)=5.17, P=0.02). Residents in both groups reported more satisfaction with managing chronic pain care after training (chi(2)=52.72, P<0.0001), though the web training was superior on subscales concerning training adequacy (chi(2)=4.94, P=0.026) and relationship quality (chi(2)=5.79, P=0.016). CONCLUSIONS: Exposure to an interactive web-based training focused on shared decision-making and communication skills was more effective than exposure to compatible practice guidelines for knowledge and self-reported competence in the management of chronic noncancer pain.