Catch the Open! A Gamified Interactive Immersion Into Open Educational Practices for Higher Education Educators.

Open Education (OE) opens up learning opportunities to, potentially, every person in the world. Additionally, it allows teachers, researchers, and practitioners to find, share, reuse, and improve existing resources under a dependable legal framework. Aiming to spread and foster the introduction of open policies in Higher Education (HE) institutions, the gamified interactive learning experience Catch the Open! was developed. Catch the Open! targets HE educators who wish to learn, or who wish to deepen their existing knowledge, about OE and Open Educational Practices (OEP). Within the gamified learning experience, the user becomes an educator, Alex, the game character, who receives a task from the Rector: to investigate how to best include OE and OEP in teaching and learning practice within the institution. Alex proceeds to explore and gather information in a web-based 2D virtual HE institution where students, colleagues, and guest researchers will help her to develop a comprehensive understanding of OE and the practical application of OEP. The educational content within Catch the Open! is underpinned by an OE competences framework for HE educators, developed in a previous phase of the Erasmus+ OpenGame project. In this paper, the design process to link pedagogical and technological approaches, which results in the Catch the Open! gamified web-based interactive application, is presented as well as the application itself. Moreover, two phases of piloting with 153 HE educators from six different HE institutions are presented. The obtained findings showed that the gamified environment helped in learning about OE. On the other hand, learners also suggested several improvement aspects of the gamified environment, such as the length of finishing a learning mission while playing.

Outpatient parenteral antimicrobial therapy for surgery patients: A comparison with previous standard of care.

BACKGROUND: Current literature reports that outpatient parenteral antimicrobial therapy (OPAT) programs improve cure rates, and reduce length of hospitalization and costs. OPAT programs are still relatively new in Canada. OBJECTIVE: To evaluate the benefits of an OPAT program initiated at a multispecialty tertiary care facility in Toronto, Ontario, compared with the previous standard of care. METHODS: The present retrospective observational study was conducted using data from a group of surgical patients who were treated for active infections. Between February 1, 2010 and November 30, 2010, a total of 108 surgical patients were enrolled in the OPAT program. Patients were matched 1:1 with historical controls discharged between January 1, 2001 and January 1, 2010 according to age, sex, type of surgery, infection and comorbidities (Charlson Comorbidity Index). Cure rate, 30-day rehospitalization and length of stay were evaluated as primary end points. RESULTS: Of 108 eligible OPAT patients, 21 were matched to the control group using the prespecified criteria. For this cohort, the OPAT program was associated with improved cure rates (OPAT 61.7% versus control 57.1%; P>0.10), reduction in rehospitalization rate (14.3% versus 28.6%; P>0.10) and reduced length of stay (10.7 versus 13.9 days, P>0.10) compared with the control group. CONCLUSIONS: For this cohort of surgery patients, the OPAT program demonstrated a trend toward improved outcomes but did not achieve statistical significance. Due to the lack of statistical power, further evaluation is required to determine the full benefit of OPAT to patients and the health care system.

HISTORIQUE: D'après les rapports bibliographiques actuels, les programmes d'antibiothérapie parentérale ambulatoire (ATPA) améliorent les taux de guérison et réduisent la durée d'hospitalisation et les coûts. Les programmes d'ATPA sont encore relativement nouveaux au Canada. OBJECTIF: Évaluer les avantages d'un programme d'ATPA lancé dans un centre de soins tertiaires multidisciplinaire de Toronto, en Ontario, par rapport aux normes de soins antérieures. MÉTHODOLOGIE: Les chercheurs ont mené la présente étude d'observation rétrospective à l'aide des données d'un groupe de patients opérés traités en raison d'infections actives. Entre le 1er février et le 30 novembre 2010, 108 patients opérés ont été inscrits au programme d'ATPA. Les patients ont été jumelés 1:1 avec des sujets témoins historiques qui ont obtenu leur congé entre le 1er janvier 2001 et le 1er janvier 2010 d'après leur âge, leur sexe, le type d'opération, l'infection et les comorbidités (indice de comorbidité de Charlson). Les paramètres principaux étaient le taux de guérison, la réhospitalisation au bout de 30 jours et la durée d'hospitalisation. RÉSULTATS: Sur les 108 patients du programme d'ATPA admissibles, 21 ont été jumelés au groupe témoin au moyen des critères pré-définis. Dans cette cohorte, le programme d'ATPA s'associait à un meilleur taux de guérison (61,7 % pour l'ATPA par rapport à 57,1 % pour le groupe témoin; P>0,10), à une réduction du taux de réhospitalisation (14,3 % par rapport à 28,6 %; P>0,10) et à diminution de la durée d'hospitalisation (10,7 par rapport à 13,9 jours, P>0,10) que dans le groupe témoin. CONCLUSIONS: Auprès de cette cohorte de patients opérés, le programme d'ATPA démontrait une tendance vers de meilleures issues, sans pour autant avoir de signification statistique. En raison de l'absence d'efficacité statistique, il faudra approfondir l'évaluation afin de déterminer les avantages du programme d'ATPA pour les patients et le système de santé.

The CXCR4/CXCR7/SDF-1 pathway contributes to the pathogenesis of Shiga toxin-associated hemolytic uremic syndrome in humans and mice.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastrointestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

Fatal pulmonary Mycobacterium xenopi in a patient with rheumatoid arthritis receiving etanercept.

In this case study, a 71 year old man with emphysema and severe rheumatoid arthritis, previously treated with a TNFα receptor antagonist, presented with progressive dyspnoea and weight loss. Thoracic imaging revealed extensive destruction of the left lung and this was associated with positive Mycobacterium xenopi cultures from respiratory samples. Anti-mycobacterial chemoptherapy was poorly tolerated and the patient subsequently died from respiratory failure and generalised wasting.

Fatal pulmonary Mycobacterium xenopi in a patient with rheumatoid arthritis receiving etanercept.

Mycobacterium xenopi is a water-related mycobacterium with low pathogenicity in humans. Little is known about the association between anti-tumour necrosis factor (TNF)alpha and non-tuberculous mycobacterial infections. The case history is presented of fatal M xenopi infection in a patient receiving anti-TNFalpha treatment.

Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome.

It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified. We used proteomic and genomic technology to systematically analyze host innate and adaptive immune responses of 40 clinically well-described patients with SARS during discrete phases of illness from the onset of symptoms to discharge or a fatal outcome. A novel signature of high IFN-alpha, IFN-gamma, and IFN-stimulated chemokine levels, plus robust antiviral IFN-stimulated gene (ISG) expression, accompanied early SARS sequelae. As acute illness progressed, SARS patients entered a crisis phase linked to oxygen saturation profiles. The majority of SARS patients resolved IFN responses at crisis and expressed adaptive immune genes. In contrast, patients with poor outcomes showed deviated ISG and immunoglobulin gene expression levels, persistent chemokine levels, and deficient anti-SARS spike antibody production. We contend that unregulated IFN responses during acute-phase SARS may culminate in a malfunction of the switch from innate immunity to adaptive immunity. The potential for the use of the gene signatures we describe in this study to better assess the immunopathology and clinical management of severe viral infections, such as SARS and avian influenza (H5N1), is therefore worth careful examination.

A novel pentamer versus pentamer approach to generating neutralizers of verotoxin 1.

Verotoxins (VTs), or shiga-like toxins, are produced by enterohemorrhagic Escherichia coli (EHEC), which cause hemorrhagic colitis and hemolytic uremic syndrome. VTs are the major virulence factors in EHEC infection due to their cytotoxicity to various types of cells. Here, we present a novel type of VT neutralizer based on pentavalent single-domain antibodies, or pentabodies. Two single-domain antibodies (sdAbs) specific for the receptor binding sites of the B subunit of VT1 (VT1B) were isolated from a naïve llama phage display library. These two sdAbs were pentamerized to generate pentameric VT neutralizers, VTI-1 and VTI-3. Both VT neutralizers bound wild type VT1B specifically with superior functional affinity. In vitro neutralization assays showed that VTI-1 and VTI-3 were able to neutralize 90% and 40%, respectively, of the cytotoxicity caused by VT1. This effort provides the basis of a novel type of VT neutralizer that can potentially be produced at a relatively low cost.

Routine use of mupirocin at the peritoneal catheter exit site and mupirocin resistance: still low after 7 years.

OBJECTIVE: The purpose of this study (the third in a series of similar studies) is to evaluate the prevalence of Staphylococcus aureus (SA), methicillin-resistant SA (MRSA) and mupirocin-resistant SA (MuRSA) carriers in a peritoneal dialysis centre where patients have been instructed to use prophylactic mupirocin ointment at the catheter exit site over the last 7 years. METHODS: Swabs were taken from catheter exit site, nares, axillae and groin in 147 chronic peritoneal dialysis out-patients between November 2003 and January 2004. Axillae/groin and nasal samples were pooled and cultured in the same medium, whereas exit site swabs were cultured separately. All SA isolated were tested for methicillin and mupirocin resistance using oxacillin screening plates and E-test strips. RESULTS: Sixteen of 147 patients (10.9%) were found to be SA carriers: of these 13 (8.8%) had a positive nasal/axillae/groin culture; two (1.4%) had both nasal/axillae/groin- and exit site-positive culture; and one (0.7%) had only exit site-positive culture. In these 16 SA carriers, we found mupirocin-resistant strains (MuRSA) in four patients (25%) and MRSA in two patients (12.5%). Among the four MuRSA carriers, one had both nasal/axillae/groin- and exit site-positive culture and three had only nasal/axillae/groin-positive culture. Three high-level resistance and one low-level resistance MuRSA carriers were isolated. One MuRSA strain was also methicillin resistant. All MRSA strains were sensitive to vancomycin and rifampicin. CONCLUSION: After 7 years' routine use of prophylactic mupirocin ointment at the catheter exit site in non-selected chronic peritoneal dialysis patients, MuRSA was found in 25% of SA strains isolated or in 2.7% of the patients. Compared with our previous study, 3 years earlier, there is no significant increase in the MuRSA prevalence in peritoneal dialysis patients who routinely apply mupirocin ointment at the catheter exit site.

West Nile virus infection in the intensive care unit: a case series and literature review.

BACKGROUND: West Nile virus (WNV) is a rapidly spreading infectious disease in North America. Critical care issues related to WNV are not well described. OBJECTIVES: Three cases of severe WNV meningoencephalitis with flaccid paralysis are reported and relevant critical care issues are highlighted. METHODS: Case series and a review of the literature. RESULTS: Three patients with WNV meningoencephalitis and flaccid paralysis were admitted to the authors' academic, tertiary-care intensive care unit (ICU) in the late summer of 2002. All three patients were middle-aged or elderly and presented with a febrile illness that preceded or coincided with their neurological symptoms. Confirmation of WNV infection was problematic because each patient had at least one initial negative serum serology test. Radiological testing yielded nonspecific results. Serial electroencephalograms were consistent with severe toxic metabolic encephalopathy in all cases. All patients had a severe, diffuse axonal polyneuropathy demonstrated by nerve conduction studies and electromyography. Prolonged mechanical ventilation resulted in ICU lengths of stay of 44 to 118 days. At one point, 21% of the ICU beds were dedicated for these patients. All three patients died in hospital - two following the withdrawal of life support. One patient demonstrated resolving encephalitis and was discharged from the ICU after a 118-day ICU stay, but later died in a step-down unit. CONCLUSIONS: The management of WNV-related critical illness creates challenges in making a timely and accurate diagnosis, and predicting patient morbidity and mortality. As a consequence, end-of-life discussions with families are especially difficult. The prolonged ICU length of stay and growing incidence of this disease may challenge limited critical care resources.

Neurological manifestations of West Nile virus infection.

BACKGROUND: Over the past four years, West Nile virus (WNV) has become a significant health issue in North America. In 2002, WNV infection made its first appearance in the human population in Canada. METHODS: Patients who presented to the University Health Network and Mount Sinai Hospital in Toronto with neurological disease attributed to WNV infection were identified and followed by the neurology service. Clinical features and results of laboratory, electrodiagnostic, radiological and pathological studies are presented. RESULTS: In August and September 2002, 26 patients were admitted with WNV infection; 14 presented with neurological illness. Encephalitis was the most common presentation (11 patients). Eleven patients developed neuromuscular disease; two at presentation and nine after encephalitis. While the majority had a motor process that localized to the anterior horn cell and/or motor neuron, two patients had evidence of a demyelinating neuropathy and one a sensorimotor axonal neuropathy. Less common manifestations included rhombencephalitis, ataxia, myelopathy and parkinsonism. Death occurred in four patients; two > 75 years of age, and two who were immunocompromised. CONCLUSIONS: The most common neurological manifestation of WNV infection was encephalitis with subsequent neuromuscular involvement. The diversity of clinical and pathological findings, however, suggests widespread involvement of the central and peripheral nervous system. A poorer prognosis for neurological recovery and overall survival was seen in older and immunocompromised patients.

West Nile virus infection in 2002: morbidity and mortality among patients admitted to hospital in southcentral Ontario.

BACKGROUND: In August and September 2002 an outbreak of West Nile virus (WNV) infection occurred in southern Ontario. We encountered a number of seriously ill patients at our hospitals. In this article we document the clinical characteristics of these cases. METHODS: We conducted a retrospective chart review of patients who came to the attention of infectious disease or neurology consultants or the microbiology laboratories at 7 hospitals in the municipalities of Toronto, Peel and Halton, Ont. Patients were included if they had been admitted to hospital or stayed overnight in the emergency department, had serological evidence of WNV infection and had clinical evidence of WNV fever, aseptic meningitis, encephalomyelitis or motor neuronopathy. RESULTS: In all, 64 patients met the inclusion criteria; 57 had encephalitis or neuromuscular weakness or both, 5 had aseptic meningitis, and 2 had WNV fever. The mean age was 61 years (range 26-87). The patients were predominantly active, middle-aged or elderly people living independently in the community. Seven patients were immunocompromised A febrile prodromal illness preceded the neurological symptoms in almost all cases. The most common neurological abnormality was decreased level of consciousness; this frequently evolved to severe lower motor neuron neuromuscular weakness. Ataxia and swallowing disorders were frequent and important problems. Sixteen patients (25%) required intubation and mechanical ventilation because of a decreased level of consciousness, inability to clear secretions or respiratory muscle weakness; 9 others had disabling muscle weakness of one or more limbs. Ten patients died. The study patients were in hospital a total of 1856 patient-days, including 532 patient-days in an intensive care unit. Only 28% (13/47) of the patients who survived encephalitis or neuromuscular weakness, or both, were discharged home without additional support. Slow turnaround time for serological test results resulted in delayed diagnosis. INTERPRETATION: The 2002 WNV infection outbreak in Ontario caused serious morbidity and mortality in the subset of patients who had encephalitis or neuromuscular weakness severe enough to require hospital admission.

Is surveillance for multidrug-resistant enterobacteriaceae an effective infection control strategy in the absence of an outbreak?

Multidrug-resistant enterobacteriaceae (MDRE) are an important cause of nosocomial infections. The effectiveness of screening for MDRE in the nonoutbreak setting in an attempt to prevent transmission is unknown. Patients admitted for new organ transplantation were screened for MDRE colonization. Prospective clinical data were collected, and pulsed-field gel electrophoresis and plasmid and integron analysis of isolates were performed. Colonized patients were not isolated except when required by standard precautions. Of the 287 patients, 69 (24%) were colonized, and 6 (9%) of the 69 developed clinical infections. Most colonizing isolates (66/69) were unique. No clinical infections resulted from patient-to-patient transmission. Analysis of clinical isolates from nonstudy patients demonstrated no evidence of transmission leading to clinical disease. The annual cost of a surveillance program was calculated at Canadian $1,130,184.44. Thus, the routine and costly use of MDRE surveillance and isolation precautions are not warranted in the absence of a clonal outbreak in this population.

Tumour necrosis factor alpha is not an essential component of verotoxin 1-induced toxicity in mice.

Previous studies have shown that tumour necrosis factor alpha (TNF-alpha) gene transcription is induced in the mouse kidney in response to Shiga-like toxin 1 (Stx 1, or Verotoxin 1, VT1) administration, suggesting that local TNF-alpha expression plays a role in renal pathogenesis caused by the toxin. Further, TNF-alpha neutralizing antibody pretreatment of mice orally infected with VT-producing Escherichia coli (VTEC) protected the animals from disease development and death. We examined the role of TNF-alpha release in response to parenteral challenge with purified VT1. Mice injected with 10- and 100-fold the 50% lethal dose (LD(50)) of VT1 showed a weak, transient elevation of serum TNF-alpha only at the higher toxin dose. TNF-alpha was not detected in the urine of mice at either dose. Treatment of BALB/c mice with a neutralizing anti-TNF-alpha antibody prior to administration of 3 LD(50) of toxin failed to protect the mice from VT1-mediated toxicity. Further, TNF-alpha knock-out mice administered 3 LD(50) of VT1 were not protected against the lethal effects of the toxin relative to the wild-type animals. These findings suggest that VT1 is a poor inducer of TNF-alpha in vivo and that the low levels of the cytokine released in response to toxin challenge do not play a direct role in potentiating the toxicity of VT1 in mice. Strong toxin accumulation in the kidney but not in the brain was demonstrated by immunohistochemistry after intraperitoneal administration of VT1. Tubular damage and extensive apoptosis in the kidney, together with a 10-fold increase in levels of blood urea nitrogen, suggest that mice died of acute renal failure.

Effectiveness of the Immigration Medical Surveillance Program for tuberculosis in Ontario.

BACKGROUND: Citizenship and Immigration Canada (CIC) screens immigrants for TB and permits those with inactive pulmonary TB to enter Canada conditionally, subject to medical surveillance; we studied this program in Ontario. METHOD: This was an administrative database study with linkage of national and provincial data. RESULTS: In 1994-95, 1,341 cases of foreign-born active TB were diagnosed and a CIC record was found for 1,095. 149 (14%) were classified for surveillance and 142 were included in the analysis. A significant proportion (39/142: 27%) were diagnosed either before or as a result of immigration screening in Canada. These persons had arrived as visitors or refugees and were excluded from further analysis. Only 21 of the remaining 103 persons (20%) with immigration screening before the diagnosis of TB adhered to surveillance. Only 1 of 16 (6%) eligible persons was given therapy to prevent future episodes of active TB. Most presented with symptoms (82/103:82%) suggesting potential for TB transmission in Ontario. INTERPRETATION: The current TB surveillance system for high-risk immigrants to Ontario is not effective in identifying and treating latent infection, and thus not effective in preventing future cases.

A mutational analysis of the globotriaosylceramide-binding sites of verotoxin VT1.

Escherichia coli verotoxin, also known as Shiga-like toxin, binds to eukaryotic cell membranes via the glycolipid Gb(3) receptors which present the P(k) trisaccharide Galalpha(1-4)Galbeta(1-4)Glcbeta. Crystallographic studies have identified three P(k) trisaccharide (P(k)-glycoside) binding sites per verotoxin 1B subunit (VT1B) monomer while NMR studies have identified binding of P(k)-glycoside only at site 2. To understand the basis for this difference, we studied binding of wild type VT1B and VT1B mutants, defective at one or more of the three sites, to P(k)-glycoside and pentavalent P(k) trisaccharide (pentaSTARFISH) in solution and Gb(3) presented on liposomal membranes using surface plasmon resonance. Site 2 was the key site in terms of free trisaccharide binding since mutants altered at sites 1 and 3 bound this ligand with wild type affinity. However, effective binding of the pentaSTARFISH molecule also required a functional site 3, suggesting that site 3 promotes pentavalent binding of linked trisaccharides at site 1 and site 2. Optimal binding to membrane-associated Gb(3) involved all three sites. Binding of all single site mutants to liposomal Gb(3) was weaker than wild type VT1B binding. Site 3 mutants behaved as if they had reduced ability to enter into high avidity interactions with Gb(3) in the membrane context. Double mutants at site 1/site 3 and site 2/site 3 were completely inactive in terms of binding to liposomal Gb(3,) even though the site 1/site 3 mutant bound trisaccharide with almost wild type affinity. Thus site 2 alone is not sufficient to confer high avidity binding to membrane-localized Gb(3). Cytotoxic activity paralleled membrane glycolipid binding. Our data show that the interaction of verotoxin with the Gb(3) trisaccharide is highly context dependent and that a membrane environment is required for biologically relevant studies of the interaction.