New proof-of-concept in viral inactivation: virucidal efficacy of 405 nm light against feline calicivirus as a model for norovirus decontamination

The requirement for novel decontamination technologies for use in hospitals is ever present. One such system uses 405 nm visible light to inactivate microorganisms via ROS-generated oxidative damage. Although effective for bacterial and fungal inactivation, little is known about the virucidal effects of 405 nm light. Norovirus (NoV) gastroenteritis outbreaks often occur in the clinical setting, and this study was designed to investigate potential inactivation effects of 405 nm light on the NoV surrogate, feline calicivirus (FCV). FCV was exposed to 405 nm light whilst suspended in minimal and organically-rich media to establish the virucidal efficacy and the effect biologically-relevant material may play in viral susceptibility. Antiviral activity was successfully demonstrated with a 4 Log10 (99.99%) reduction in infectivity when suspended in minimal media evident after a dose of 2.8 kJ cm−2. FCV exposed in artificial faeces, artificial saliva, blood plasma and other organically rich media exhibited an equivalent level of inactivation using between 50–85% less dose of the light, indicating enhanced inactivation when the virus is present in organically-rich biologically-relevant media. Further research in this area could aid in the development of 405 nm light technology for effective NoV decontamination within the hospital environment

Cervicofacial Actinomycosis in the Pediatric Population: Presentation and Management

Background: Infection caused by Actinomyces species is a rare cause of head and neck infection in children. This chronic cervicofacial infection can present with localized swelling, abscess formation, sinus drainage and can be complicated by osteomyelitis. Methods: Presented are 2 pediatric cases of secondary actinomycosis in the context of congenital lesions: 1 patient with a previously excised preauricular sinus and another with a persistent sublingual mass. A comprehensive literature search was conducted for reported cases of pediatric actinomycosis in the cervicofacial region. Results: Both cases presented were successfully treated with a combination of complete surgical excision of the lesions and prolonged antibiotic therapy. Thirty-four pediatric cases of cervicofacial actinomycosis are reviewed, 2 presented herein, and 32 from the published literature. There was equal gender distribution and the median age was 7.5 years. The most common site for infection was the submandibular area. Four (12%) of cases arose in pre-existing congenital lesions. Most patients were treated with penicillin-based antibiotics for a median duration of 6 months following surgical excision or debridement. Conclusions: Actinomycosis is a rare infection of the cervicofacial region; secondary infections arising from congenital lesions of the head and neck are even more rare. A previously excised pre-auricular sinus and a sublingual dermoid cyst are not previously reported sites of infection. Actinomycosis should be suspected in chronically draining sinuses of the head and neck region and confirmed through anaerobic culture. Osteomyelitis is a potential complication and magnetic resonance (MR) imaging is warranted. Long-term antibiotic therapy with a penicillin-based antibiotic and surgical excision should be considered

Women with coronary artery disease report worse health-related quality of life outcomes compared to men

BACKGROUND: Although there have been substantial medical advances that improve the outcomes following cardiac ischemic events, gender differences in the treatment and course of recovery for patients with coronary artery disease (CAD) continue to exist. There is a general paucity of data comparing the health related quality of life (HRQOL) in men and women undergoing treatment for CAD. The purpose of this study was to compare HRQOL outcomes of men and women in Alberta, at one-year following initial catheterization, after adjustment for known demographic, co-morbid, and disease severity predictors of outcome. METHOD: The HRQOL outcome data were collected by means of a self-reported questionnaire mailed to patients on or near the one-year anniversary of their initial cardiac catheterization. Using the Seattle Angina Questionnaire (SAQ), 5 dimensions of HRQOL were measured: exertional capacity, anginal stability, anginal frequency, quality of life and treatment satisfaction. Data from the APPROACH registry were used to risk-adjust the SAQ scale scores. Two analytical strategies were used including general least squares linear modeling, and proportional odds modeling sometimes referred to as the "ordinal logistic modeling". RESULTS: 3392 (78.1%) patients responded to the follow-up survey. The adjusted proportional odds ratios for men relative to women (PORs > 1 = better) indicated that men reported significantly better HRQOL on all 5 SAQ dimensions as compared to women. (PORs: Exertional Capacity 3.38 (2.75–4.15), Anginal Stability 1.23 (1.03–1.47), Anginal Frequency 1.70 (1.43–2.01), Treatment Satisfaction 1.27 (1.07–1.50), and QOL 1.74 (1.48–2.04). CONCLUSIONS: Women with CAD consistently reported worse HRQOL at one year follow-up compared to men. These findings underline the fact that conclusions based on research performed on men with CAD may not be valid for women and that more gender-related research is needed. Future studies are needed to further examine gender differences in psychosocial adjustment following treatment for CAD, as adjustment for traditional clinical variables fails to explain sex differences in health related quality of life outcomes

A live, impaired-fidelity coronavirus vaccine protects in an aged, immunocompromised mouse model of lethal disease

Live-attenuated RNA virus vaccines are efficacious but subject to reversion to virulence. Among RNA viruses, replication fidelity is recognized as a key determinant of virulence and escape from antiviral therapy; increased fidelity is attenuating for some viruses. Coronavirus replication fidelity is approximately 20-fold greater than that of other RNA viruses and is mediated by a 3′-5′ exonuclease activity (ExoN) that likely functions in RNA proofreading. In this study, we demonstrate that engineered inactivation of SARS-CoV ExoN activity results in a stable mutator phenotype with profoundly decreased fidelity in vivo and attenuation of pathogenesis in young, aged, and immunocompromised mouse models of human SARS. The ExoN inactivation genotype and mutator phenotype are stable and do not revert to virulence, even after serial passage or long-term persistent infection in vivo. Our approach represents a strategy with potential for broad applications for the stable attenuation of coronaviruses and possibly other RNA viruses

Riding the knowledge translation roundabout: lessons learned from the Canadian Institutes of Health Research Summer Institute in knowledge translation

<p>Abstract</p> <p>Background</p> <p>Funding the education and training of the next generation of health researchers is a key mandate of the Canadian Institutes of Health Research (CIHR) knowledge translation (KT) portfolio. The field of KT is growing daily; thus, the training and development of a new generation of KT researchers is essential.</p> <p>Methods</p> <p>Using curriculum documents, participant evaluations, and self-reflection, this paper describes a unique Summer Institute hosted by the CIHR in Cornwall, Ontario, Canada. We outline the key aspects of a successful training initiative that could inform organizations and agencies worldwide with an interest in or who have a mandate for KT.</p> <p>Results</p> <p>This work provides potential funders, faculty, and students with an inside look into the purpose, process, and outcomes of such training initiatives.</p> <p>Conclusion</p> <p>National and international KT organizations, research institutions, and funding agencies are encouraged to consider replicating the training model employed here, as investment into KT personnel will foster the advancement of the field within and beyond local borders.</p> <p>'To the individual who devotes his/her life to science, nothing can give more happiness than when the results immediately find practical application. There are not two sciences. There is science and the application of science, and these two are linked as the fruit is to the tree.' – Louis Pasteur, 1871 (from presentation by Ian Graham, 2008 CIHR Knowledge Translation Summer Institute)</p

Paraoxonase 1 Phenotype and Mass in South Asian versus Caucasian Renal Transplant Recipients

South Asian renal transplant recipients have a higher incidence of cardiovascular disease compared with Caucasian renal transplant recipients. We carried out a study to determine whether paraoxonase 1, a novel biomarker for cardiovascular risk, was decreased in South Asian compared with Caucasian renal transplant recipients. Subjects were matched two to one on the basis of age and sex for a total of 129 subjects. Paraoxonase 1 was measured by mass, arylesterase activity, and two-substrate phenotype assay. Comparisons were made by using a matched design. The frequency of PON1 QQ, QR and RR phenotype was 56%, 37%, and 7% for Caucasian subjects versus 35%, 44%, and 21% for South Asian subjects (χ2 = 7.72, P = 0.02). PON1 mass and arylesterase activity were not significantly different between South Asian and Caucasian subjects. PON1 mass was significantly associated with PON1 phenotype (P = 0.0001), HDL cholesterol (P = 0.009), LDL cholesterol (P = 0.02), and diabetes status (P < 0.05). Arylesterase activity was only associated with HDL cholesterol (P = 0.003). Thus the frequency of the PON1 RR phenotype was higher and that of the QQ phenotype was lower in South Asian versus Caucasian renal transplant recipients. However, ethnicity was not a significant factor as a determinant of PON1 mass or arylesterase activity, with or without analysis including PON1 phenotype. The two-substrate method for determining PON1 phenotype may be of value for future studies of cardiovascular complications in renal transplant recipients

Capsular polysaccharide conformations in pneumococcal serotypes 19F and 19A

Streptococcus pneumoniae is a significant pathogen in children. Although the PCV7 pneumococcal conjugate vaccine has reduced pneumococcal disease, non-vaccine serotype 19A infection has increased, despite expectations of cross-protection from vaccine serotype 19F. Serotype 19A is included in the new PCV13 vaccine, but not in PCV10. In the solution simulations of 19F and 19A oligosaccharide chains reported here, both polysaccharides form unstructured random coils, with inflexible repeat units linked by mobile phosphodiester linkages. However, there are clear conformational differences. In the 19F repeat unit, the rhamnose residue is nearly orthogonal to the other residues, whereas 19A has residues in similar orientations. This finding is corroborated by key inter-residue distances calculated from NMR NOESY experiments. Further, 19F is predominantly in extended conformations, whereas 19A exhibits a high prevalence of tight hairpin bends. These conformational differences may account for a lack of antibody cross-protection between serotypes 19F and 19A

Use of Hemagglutinin Stem Probes Demonstrate Prevalence of Broadly Reactive Group 1 Influenza Antibodies in Human Sera.

A better understanding of the seroprevalence and specificity of influenza HA stem-directed broadly neutralizing antibodies (bNAbs) in the human population could significantly inform influenza vaccine design efforts. Here, we utilized probes comprising headless, HA stabilized stem (SS) to determine the prevalence, binding and neutralization breadth of antibodies directed to HA stem-epitope in a cross-sectional analysis of the general population. Five group-1 HA SS probes, representing five subtypes, were chosen for this analyses. Eighty-four percent of samples analyzed had specific reactivity to at least one probe, with approximately 60% of the samples reactive to H1 probes, and up to 45% reactive to each of the non-circulating subtypes. Thirty percent of analyzed sera had cross-reactivity to at least four of five probes and this reactivity could be blocked by competing with F10 bNAb. Binding cross-reactivity in sera samples significantly correlated with frequency of H1H5 cross-reactive B cells. Interestingly, only 33% of the cross-reactive sera neutralized both H1N1 and H5N1 pseudoviruses. Cross-reactive and neutralizing antibodies were more prevalent in individuals >50 years of age. Our data demonstrate the need to use multiple HA-stem probes to assess for broadly reactive antibodies. Further, a universal vaccine could be designed to boost pre-existing B-cells expressing stem-directed bNAbs

Cognitive and physical fatigue—the experience and consequences of ‘brain fog’ after spontaneous coronary artery dissection: a qualitative study

AIMS: Brain fog and fatigue are common issues after acute coronary syndrome. However, little is known about the nature and impact of these experiences in spontaneous coronary artery dissection (SCAD) survivors. The aims of this study were to understand the experiences of brain fog and the coping strategies used after SCAD.METHODS AND RESULTS: Participants were recruited from the Victor Chang Cardiac Research Institute Genetics Study database and were considered eligible if their event occurred within 12-months. Seven semi-structured online focus groups were conducted between December to January 2021-2022, with this study reporting findings related to brain fog and fatigue. Interviews were transcribed and thematically analysed using an iterative approach. Participants (N=30) were a mean age of 52.2 ((9.5) and mostly female (n=27, 90%). The overarching theme of brain fog after SCAD included four main themes: how brain fog is experienced, perceived causes, impacts, and how people cope. Experiences included memory lapses, difficulty concentrating and impaired judgement, and perceived causes included medication, fatigue and tiredness, and menopause and hormonal changes. Impacts of brain fog included rumination, changes in self-perception, disruption to hobbies/pastimes, and limitations at work. Coping mechanisms included setting reminders and expectations, being one's own advocate, lifestyle and self-determined medication adjustments, and support from peers.CONCLUSION: Brain fog is experienced by SCAD survivors and the impacts are varied and numerous, including capacity to work. SCAD survivors reported difficulty understanding causes and found their own path to coping. Recommendations for clinicians are provided.</p