SARS-CoV-2 Viral Replication Persists in the Human Lung for Several Weeks after Symptom Onset.

Rationale: In the upper respiratory tract, replicating (culturable) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recoverable for ∼4-8 days after symptom onset, but there is a paucity of data about the frequency and duration of replicating virus in the lower respiratory tract (i.e., the human lung).Objectives: We undertook lung tissue sampling (needle biopsy) shortly after death in 42 mechanically ventilated decedents during the Beta and Delta waves. An independent group of 18 ambulatory patients served as a control group.Methods: Lung biopsy cores from decedents underwent viral culture, histopathological analysis, electron microscopy, transcriptomic profiling, and immunohistochemistry.Measurements and Main Results: Thirty-eight percent (16 of 42) of mechanically ventilated decedents had culturable virus in the lung for a median of 15 days (persisting for up to 4 wk) after symptom onset. Lung viral culture positivity was not associated with comorbidities or steroid use. Delta but not Beta variant lung culture positivity was associated with accelerated death and secondary bacterial infection (P < 0.05). Nasopharyngeal culture was negative in 23.1% (6 of 26) of decedents despite lung culture positivity. This hitherto undescribed biophenotype of lung-specific persisting viral replication was associated with an enhanced transcriptomic pulmonary proinflammatory response but with concurrent viral culture positivity.Conclusions: Concurrent rather than sequential active viral replication continues to drive a heightened proinflammatory response in the human lung beyond the second week of illness and was associated with variant-specific increased mortality and morbidity. These findings have potential implications for the design of interventional strategies and clinical management of patients with severe coronavirus disease (COVID-19).

Advances in PAH mixture toxicology enabled by zebrafish.

Polycyclic aromatic hydrocarbons (PAHs) are a class of organic compounds produced by a variety of petrogenic and pyrogenic sources. PAHs inherently occur in the environment in complex mixtures. The early life-stage zebrafish model is a valuable tool for high-throughput screening (HTS) for toxicity of complex chemical mixtures due to its rapid development, high fecundity, and superb sensitivity to chemical insult. Zebrafish are amenable to exposure to surrogate mixtures as well as extracts of environmental samples and effect-directed analysis. In addition to its utility to HTS, the zebrafish has proven an excellent model for assessing chemical modes of action and identifying molecular initiating and other key events in an Adverse Outcome Pathway framework. Traditional methods of assessing PAH mixture toxicity prioritize carcinogenic potential and lack consideration of non-carcinogenic modes of action, assuming a similar molecular initiating event for all PAHs. Recent work in zebrafish has made it clear that while PAHs belong to the same chemical class, their modes of action can be divergent. Future research should use zebrafish to better classify PAHs by their bioactivity and modes of action to better understand mixture hazards.

Protocol for a qualitative pilot study to explore ethical issues and stakeholder trust in the use of normothermic regional perfusion in organ donation in Canada.

INTRODUCTION: The process of controlled organ donation after circulatory determination of death (cDCDD) results in ischaemic injury to organs and leads to poorer outcomes in organ recipients. Although not yet used in Canada, normothermic regional perfusion (NRP) is a perfusion technology used postmortem with cDCDD donors to selectively restore perfusion of oxygenated blood to target organs in situ, reversing ischaemic injury and improving organ viability and post-transplant outcomes. However, NRP poses significant ethical challenges. To preserve trust in deceased donation, these ethical challenges must be addressed to the satisfaction of Canadian stakeholders before NRP's implementation. This study will identify ethical issues pertaining to NRP and explore perspectives of NRP among key stakeholders. By developing an explanatory framework delineating how stakeholder perceptions of NRP's ethical implications impact trust in Canada's donation and transplantation systems, this study will inform the development of responsible policy on NRP's use in Canada. METHODS AND ANALYSIS: This study includes two workstreams. Workstream 1 is a scoping review of medical and bioethical literature to identify ethical issues stemming from NRP. We will apply a common search string across Medline, PubMed (other than Medline) and Embase to identify relevant articles. We will identify grey literature through Google searches, websites of organ donation organisations and consultation with our research network. No date limits will be applied. All peer-reviewed publications, commentaries, editorials or documents that engage with ethical issues in NRP (or conceptual and empirical issues as they relate to these ethical issues) will be included. News articles, conference abstracts and publications not in English will be excluded. Workstream 2 consists of interviews with healthcare providers, institutional stakeholders, organ recipients and deceased donors' family members (n=24-36), as well as focus groups with healthcare providers involved in deceased donation and transplantation (n=20-32). Constructivist grounded theory methodology will guide data collection and analysis in workstream 2. ETHICS AND DISSEMINATION: This study was approved by Western University's research ethics committee (Western REM; ID: 120001). All participants will be asked to provide written informed consent to participate. Findings will be shared with Canadian organ donation and transplantation organisations, presented at national conferences and published in medical journals.

Development and Evaluation of a Faculty Teaching Boot Camp Before and During the COVID-19 Pandemic.

Introduction Medical faculty often assume teaching responsibilities without formal training in teaching skills. The purpose of this study was to design, implement, and evaluate boot camp workshop training faculty in basic teaching competencies. We also describe the transition to a virtual format necessitated by the COVID-19 pandemic. Methods The workshop content was derived from a needs assessment survey and discussion with content experts. Four main content areas were identified: setting expectations, giving feedback, evaluating learners, and teaching in specific settings (outpatient clinics, inpatient wards, procedures/surgery, and small groups). The initial boot camp was a four-hour in-person event. The following year, the boot camp was offered via online videoconference. We used a pre-post survey to assess participant reaction and knowledge acquisition from session content. Results A total of 30 local faculty attended the 2020 in-person boot camp, while 105 faculty from across the state attended the 2021 online boot camp. Statistically significant increases in post-knowledge scores were identified for two sessions in the 2020 boot camp and four sessions in 2021. The participants rated both boot camps favorably with no significant difference between the in-person and online presentations for most ratings but were less satisfied with networking opportunities in the online boot camp. Discussion We describe an effective faculty development boot camp teaching core competencies for medical clinician-educators. We were able to leverage the online teleconferencing platform to deliver the content to a larger number of preceptors at distant sites without sacrificing outcomes of participant satisfaction and improvement in knowledge scores. The online model allowed busy clinicians to participate while multitasking. Comments also highlighted the importance of having an engaged moderator during the online event. Conclusions Many medical schools utilize preceptors in distant locations. We demonstrated the feasibility of reaching a much larger and geographically widespread group of clinical preceptors using a virtual format while still showing improvement in knowledge scores relating to workshop content. For future faculty development, we propose that hybrid models with both in-person and virtual components will be effective in meeting the needs of a geographically distributed faculty.

Current Use, Capacity, and Perceived Barriers to the Use of Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest in Canada.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a therapeutic option for refractory cardiac arrest. We sought to perform an environmental scan to describe ECPR utilization in Canada and perceived barriers for application to out-of-hospital cardiac arrest (OHCA). METHODS: This was a national cross-sectional study. We identified all cardiovascular surgery- and extracorporeal membrane oxygenation (ECMO)-capable hospitals in Canada and emergency medical services (EMS) agencies delivering patients to those centres. We requested the medical lead from each hospital's ECMO service and each EMS agency to submit data regarding ECMO and ECPR utilization, as well as perceived barriers to ECPR provision for OHCA. RESULTS: We identified and received survey data from 39 of 39 Canadian hospital institutions and 21 of 22 EMS agencies. Of hospitals, 38 (97%) perform ECMO and 27 (69%) perform ECPR (74% of which perform ≤5 cases per year). Of the 18 (46%) sites offering ECPR for OHCA, 8 apply a formal protocol for eligibility and initiation procedures. EMS agencies demonstrate heterogeneity with intra-arrest transport practices. The primary rationale for nontransport of refractory OHCA is that hospital-based care offers no additional therapies. Perceived barriers to the use of ECPR for OHCA were primarily related to limited evidence supporting its use, rather than resources required. CONCLUSION: Many Canadian cardiovascular surgery- or ECMO-equipped hospitals use ECPR; roughly half employ ECPR for OHCAs. Low case volumes and few formal protocols indicate that this is not a standardized therapy option in most centres. Increased application may be dependent on a stronger evidence base including data from randomized clinical trials currently underway.

CONTEXTE: La réanimation cardiorespiratoire (RCR) extracorporelle est une option thérapeutique en cas d'arrêt cardiaque réfractaire. Nous avons voulu faire une analyse contextuelle de l'utilisation de la RCR extracorporelle au Canada et des obstacles perçus quant à son emploi dans les cas d'arrêt cardiaque en dehors de l'hôpital. MÉTHODOLOGIE: Il s'agissait d'une étude nationale transversale. Nous avons repéré tous les hôpitaux en mesure d'effectuer des chirurgies cardiovasculaires et d'offrir l'oxygénation extracorporelle au Canada et les fournisseurs de services médicaux d'urgence (SMU) transportant les patients vers ces centres. Nous avons demandé au chef médical du service d'oxygénation extracorporelle de chacun des hôpitaux et de chacun des fournisseurs de SMU de présenter leurs données concernant l'utilisation de l'oxygénation extracorporelle et de la RCR extracorporelle, ainsi que les obstacles perçus quant à l'emploi de la RCR extracorporelle dans les cas d'arrêt cardiaque en dehors de l'hôpital. RÉSULTATS: Nous avons obtenu les données de 39 des 39 établissements hospitaliers canadiens ciblés, et de 21 des 22 fournisseurs de SMU. Parmi les hôpitaux, 38 (97%) utilisent l'oxygénation extracorporelle et 27 (69 %), la RCR extracorporelle (74 % ayant eu recours à celle-ci dans ≤ 5 cas par année). Parmi les 18 (46 %) centres offrant la RCR extracorporelle en cas d'arrêt cardiaque en dehors de l'hôpital, 8 appliquaient un protocole officiel pour l'admissibilité et les procédures de mise en place. Les fournisseurs de SMU ont montré des pratiques hétérogènes concernant la réanimation en déplacement. La principale raison justifiant de ne pas transporter les patients présentant un arrêt cardiaque réfractaire en dehors de l'hôpital est que les soins en milieu hospitalier n'offrent pas de traitements additionnels. Les obstacles perçus quant à l'emploi de la RCR extracorporelle dans les cas d'arrêt cardiaque en dehors de l'hôpital étaient principalement liés au peu de données appuyant son utilisation, plutôt qu'aux ressources nécessaires. CONCLUSION: De nombreux hôpitaux canadiens équipés pour la chirurgie cardiovasculaire et l'oxygénation extracorporelle utilisent la RCR extracorporelle; environ la moitié d'entre eux utilisent la RCR extracorporelle en cas d'arrêt cardiaque en dehors de l'hôpital. Le faible nombre de cas et le peu de protocoles officiels indiquent qu'il ne s'agit pas d'une option de traitement standardisée dans la plupart des centres. Une utilisation plus fréquente pourrait nécessiter davantage de données probantes, y compris les résultats des études cliniques à répartition aléatoire qui sont en cours.

The chemistry and toxicology of vaping.

Vaping is the process of inhaling and exhaling an aerosol produced by an e-cigarette, vape pen, or personal aerosolizer. When the device contains nicotine, the Food and Drug Administration (FDA) lists the product as an electronic nicotine delivery system or ENDS device. Similar electronic devices can be used to vape cannabis extracts. Over the past decade, the vaping market has increased exponentially, raising health concerns over the number of people exposed and a nationwide outbreak of cases of severe, sometimes fatal, lung dysfunction that arose suddenly in otherwise healthy individuals. In this review, we discuss the various vaping technologies, which are remarkably diverse, and summarize the use prevalence in the U.S. over time by youths and adults. We examine the complex chemistry of vape carrier solvents, flavoring chemicals, and transformation products. We review the health effects from epidemiological and laboratory studies and, finally, discuss the proposed mechanisms underlying some of these health effects. We conclude that since much of the research in this area is recent and vaping technologies are dynamic, our understanding of the health effects is insufficient. With the rapid growth of ENDS use, consumers and regulatory bodies need a better understanding of constituent-dependent toxicity to guide product use and regulatory decisions.

Newcomer knowledge, attitudes, and beliefs about human papillomavirus (HPV) vaccination.

BACKGROUND: Human Papillomavirus (HPV) is the most common sexually transmitted infection in Canada and around the world. Vaccination is an effective prevention strategy, but uptake is low, especially among newcomers to Canada. We sought to understand newcomers' knowledge, attitudes, and beliefs (KAB) on HPV and HPV vaccination and their role in HPV vaccine acceptance. METHODS: Newcomers were defined as individuals born outside Canada, (i.e., individuals born in a different country, the majority of whom are immigrants or refugees, but also includes students and undocumented migrants). Eligible participants were newcomers, aged 16 or older and who could read or write in English, French or Arabic. Surveys were administered in two community health centres in Ottawa, Canada that primarily engage with newcomer populations. Follow-up interviews were conducted either at the community health centre or over the phone, depending on participants' preferences. RESULTS: Fifty participants completed the survey, the majority of whom were women (74%) and spoke Arabic as their first language (54%). Seven participants completed supplemental interviews to complement their survey responses. The majority (70%) of participants had not previously heard of HPV. Less than half (46%) knew that the vaccine is effective in preventing certain types of cancer; nearly 40% incorrectly believed the vaccine could cure HPV. Qualitative interviews supported the survey findings. CONCLUSIONS: Despite a lack of HPV knowledge due to cultural and language barriers, there is still a strong desire among newcomers to receive the vaccine, especially when accompanied by a physician recommendation. Cultural and language-appropriate resources are needed to help newcomers make informed vaccination decisions and promote HPV vaccine uptake.

The Urgent Need to Respond to HIV- and HCV-Related Risk Practices among Youth in Ottawa Who Smoke Crack.

BACKGROUND: A community-based research project, Project Rock sought to provide evidence to respond to the community-identified need to more fully understand the parameters of the social and risk profiles of youth in Ottawa who smoked crack. Objectives: In this article we examine engagement in HIV and HCV risk-related smoking practices, and experiences accessing safer inhalation supplies with the objective of identifying potential intervention points and associated harm reduction interventions to initiate and support safer inhalation practices. Methods: The study comprised four sequential components - formation and facilitation of a Youth Project team, qualitative interviews, and member checking workshops - each component building on the preceding and all contributing to the final and fourth component of the interviewer-administered quantitative survey from which data for this article are drawn. Eligibility criteria: capable of informed consent; aged between 16 and 25 years; had ever injected drugs or had ever tried crack or had used two or more hard drugs in the three months preceding their interview. Recruitment cards distributed by community agencies, honoraria and debriefing offered. Separate consent obtained for collection of finger prick blood samples for HIV and HCV laboratory testing. Results: 125 young people completed personal interviews in November 2013. This article is restricted to those 97 participants who had smoked crack. High rates of engagement in documented HIV- and HCV-related crack smoking practices were reported including nonuse of mouthpieces, use of non-recommended smoking devices and frequent engagement in equipment sharing; engagement compounded by the heightened confirmed prevalence of HCV. Conclusion: The youth in our study explained the utility of crack in their lives. Given the mental health drivers of engagement, ease of accessibility and availability, engagement in smoking crack is clearly likely to continue, firmly indicating the urgent necessity to ensure its safer use through gender neutral, youth-specific enhanced programming and resource distribution.

Effect of Radiation on DCE-MRI Pharmacokinetic Parameters in a Rabbit Model of Compromised Maxillofacial Wound Healing: A Pilot Study.

PURPOSE: Osteoradionecrosis (ORN), a potentially debilitating complication of maxillofacial radiation, continues to present a challenging clinical scenario, with limited treatment options that often fail. Translational animal models that can accurately mimic the human characteristics of the condition are lacking. In the present pilot study, we aimed to characterize the effects of radiation on the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) pharmacokinetic parameters in a rabbit model of compromised maxillofacial wound healing to determine its potential as a translational model of ORN. MATERIALS AND METHODS: An experimental group underwent fractionated radiation of the mandible totaling 36 Gy. At 4 weeks after irradiation, the experimental and control groups (n = 8 rabbits each) underwent a surgical procedure to create a critical size defect in the mandibular bone. DCE-MRI scans were acquired 1 week after arrival (baseline; time point 1), 4 weeks after completion of irradiation in the experimental group (just before surgery, time point 2), and 4 weeks after surgery (time point 3). RESULTS: No differences in the analyzed DCE-MRI parameters were noted within the experimental or control group between the baseline values (time point 1) and those after irradiation (time point 2). The whole blood volume fraction (vb) in the experimental group was increased compared with that in the control group after irradiation (time point 2; P < .05). After surgery (time point 3), both the forward flux rate of contrast from blood plasma and the extracellular extravascular space and the vb were increased in the control group compared with the experimental group (P < .05). CONCLUSIONS: The results of the present study suggest that DCE-MRI of a rabbit model of compromised maxillofacial wound healing could reflect the DCE-MRI characteristics of human patients with ORN and those at risk of developing the condition. Future studies will focus on further characterization of this rabbit model as a translational preclinical model of ORN.

Healthcare provider perspectives on the uptake of the human papillomavirus vaccine among newcomers to Canada: a qualitative study.

Human papillomavirus is among the most common sexually transmitted infections in the world. Newcomers, defined in Canada as foreign-born individuals who are either immigrants or refugees, but may also include students and undocumented migrants, face numerous barriers to HPV vaccination. This study sought to understand, from the perspective of healthcare providers, barriers and facilitators to HPV vaccination, and recommendations to improve HPV vaccine uptake among newcomers. Semi-structured interviews were conducted with 10 healthcare providers between March and April 2018. Data were analyzed at the manifest level using a Qualitative Content Analysis approach. Categories of barriers to vaccination included: access, communication, knowledge, culture, and provider-related factors. Facilitators included targeted health promotion; understanding the relevance of HPV vaccination; trusting the healthcare system; and cultural sensitivity. Two overarching recommendations were to publicly fund the HPV vaccine, and enhance language- and culturally-appropriate health promotion activities. Further research should explore informational desires and needs from the perspective of newcomers to inform strategies to promote equitable HPV vaccine coverage.

Barriers to immunization among newcomers: A systematic review.

INTRODUCTION: Currently, there is a lack of comprehensive evidence exploring vaccine decision-making among newcomers. We conducted a systematic review of qualitative studies aimed at identifying factors that influence newcomers' decision-making with regards to vaccination. METHODS: We conducted a search of MEDLINE, EMBASE, CINAHL and Cochrane Central. To be included, studies needed to employ a qualitative methodology and address newcomer attitudes, beliefs, and/or perceptions regarding vaccination. Two independent reviewers screened the articles for relevant information and applied a content analysis methodology to code the identified barriers. RESULTS: Twenty-one studies were included in this review, and four types of barriers were identified: cultural factors, knowledge barriers, insufficient access to healthcare, and vaccine hesitancy. Insufficient knowledge about vaccination and the virus being prevented and concerns about safety were the most commonly reported barriers. A sub-analysis of barriers specific to HPV indicated that cultural beliefs about sexuality and incomplete knowledge about the role of HPV in the development of cervical cancer are major barriers to vaccine uptake. CONCLUSION: Strategies to improve vaccination uptake in newcomers should consider focusing on the barriers identified in this review while taking into account the unique opportunities for promoting uptake within newcomer populations.

Serotonin-Modulating Antidepressants and Risk of Bleeding after Trauma.

Serotonin-modulating antidepressants have been associated with increased risk of gastrointestinal bleeding and increased blood loss during elective surgery. This study sought to investigate the effect of preinjury selective-serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) use on transfusion requirements after trauma, and to evaluate whether resumption of SSRI/SNRI after trauma may worsen bleeding risk. This was a retrospective matched-cohort study evaluating patients with solid organ injury. Preinjury SSRI/SNRI users were matched to non-SSRI/SNRI users based on age, preinjury aspirin use, Injury Severity Score, and abdominal Abbreviated Injury Severity Score. The primary endpoint was transfusion requirement during hospitalization. The absolute need for transfusion was higher in SSRI/SNRI users throughout hospitalization (50.9% vs 37.3%, P = 0.02). After logistic multivariate analysis, SSRI/SNRI users were more likely to require transfusion at 24 hours (odds ratio (95% confidence interval): 2.73 (1.41, 5.29), P = 0.003), but this difference did not persist for overall hospitalization (odds ratio (95% confidence interval): 1.32 (0.74, 2.36), P = 0.35). Fewer patients restarted on SSRI/SNRI therapy within 72 hours required packed red blood cell transfusion compared with those who were restarted later or not at all (43.2% vs 60.3%; P = 0.04). Preinjury use of serotonin-modulating antidepressants led to an increased requirement of blood transfusions after solid organ injury. Although clinicians should weigh bleeding risk before reinitiation of SSRI/SNRI, the results of this study indicate that reasonable efforts to restart these medications after stabilization do not result in further risk for transfusion.

The chronic and evolving neurological consequences of traumatic brain injury.

Traumatic brain injury (TBI) can have lifelong and dynamic effects on health and wellbeing. Research on the long-term consequences emphasises that, for many patients, TBI should be conceptualised as a chronic health condition. Evidence suggests that functional outcomes after TBI can show improvement or deterioration up to two decades after injury, and rates of all-cause mortality remain elevated for many years. Furthermore, TBI represents a risk factor for a variety of neurological illnesses, including epilepsy, stroke, and neurodegenerative disease. With respect to neurodegeneration after TBI, post-mortem studies on the long-term neuropathology after injury have identified complex persisting and evolving abnormalities best described as polypathology, which includes chronic traumatic encephalopathy. Despite growing awareness of the lifelong consequences of TBI, substantial gaps in research exist. Improvements are therefore needed in understanding chronic pathologies and their implications for survivors of TBI, which could inform long-term health management in this sizeable patient population.

Distinct phosphodiesterase 5A-containing compartments allow selective regulation of cGMP-dependent signalling in human arterial smooth muscle cells.

Cyclic GMP (cGMP) translates and integrates much of the information encoded by nitric oxide (NO·) and several natriuretic peptides, including the atrial natriuretic peptide (ANP). Previously, we reported that integration of a cGMP-specific cyclic nucleotide phosphodiesterase, namely phosphodiesterase 5A (PDE5A), into a protein kinase G (PKG)- and inositol-1,4,5-trisphosphate receptor (IP3R)-containing endoplasmic reticulum (ER) signalosome allows localized control of PDE5A activity and of PKG-dependent inhibition of IP3-mediated release of ER Ca2+ in human platelets. Herein, we report that PDE5A integrates into an analogous signalosome in human arterial smooth muscle cells (HASMC), wherein it regulates muscarinic agonist-dependent Ca2+ release and is activated selectively by PKG-dependent phosphorylation. In addition, we report that PDE5A also regulates HASMC functions via events independent of PKG, but rather through actions coordinated by competitive cGMP-mediated inhibition of cAMP hydrolysis by the so-called cGMP-inhibited cAMP PDE, namely phosphodiesterase 3A (PDE3A). Indeed, we show that ANP increases both cGMP and cAMP levels in HASMC and promotes phosphorylation of vasodilator-stimulated phospho-protein (VASP) at each the PKG and PKA phospho-acceptor sites. Since selective inhibition of PDE5 decreased DNA synthesis and chemotaxis of HASMC, and that PDE3A knockdown obviated these effects, our findings are consistent with a role for a PDE5A-PDE3A-PKA axis in their regulation. Our findings provide insight into the existence of distinct "pools" of PDE5A in HASMC and support the idea that these discrete compartments regulate distinct cGMP-dependent events. As a corollary, we suggest that it may be possible to target these distinct PDE5A-regulated pools and in so-doing differentially impact selected cGMP-regulated functions in these cells.

Electrochemical Aptatoxisensor Responses on Nanocomposites Containing Electro-Deposited Silver Nanoparticles on Poly(Propyleneimine) Dendrimer for the Detection of Microcystin-LR in Freshwater.

A sensitive and reagentless electrochemical aptatoxisensor was developed on cobalt (II) salicylaldiimine metallodendrimer (SDD-Co(II)) doped with electro-synthesized silver nanoparticles (AgNPs) for microcystin-LR (L, l-leucine; R, l-arginine), or MC-LR, detection in the nanomolar range. The GCE|SDD-Co(II)|AgNPs aptatoxisensor was fabricated with 5' thiolated aptamer through self-assembly on the modified surface of the glassy carbon electrode (GCE) and the electronic response was measured using cyclic voltammetry (CV). Specific binding of MC-LR with the aptamer on GCE|SDD-Co(II)|AgNPs aptatoxisensor caused the formation of a complex that resulted in steric hindrance and electrostatic repulsion culminating in variation of the corresponding peak current of the electrochemical probe. The aptatoxisensor showed a linear response for MC-LR between 0.1 and 1.1 µg·L-1 and the calculated limit of detection (LOD) was 0.04 µg·L-1. In the detection of MC-LR in water samples, the aptatoxisensor proved to be highly sensitive and stable, performed well in the presence of interfering analog and was comparable to the conventional analytical techniques. The results demonstrate that the constructed MC-LR aptatoxisensor is a suitable device for routine quantification of MC-LR in freshwater and environmental samples.

Informed consent: do information pamphlets improve post-operative risk-recall in patients undergoing total thyroidectomy: prospective randomized control study.

BACKGROUND: Informed consent consists of basic five elements: voluntarism, capacity, disclosure, understanding, and ultimate decision-making. Physician disclosure, patient understanding, and information retention are all essential in the doctor-patient relationship. This is inclusive of helping patients make and manage their decisions and expectations better and also to deal with any consequences and/or complications that arise. This study investigates whether giving patients procedure-specific handouts pre-operatively as part of the established informed consent process significantly improves overall risk-recall following surgery. These handouts outline the anticipated peri-operative risks and complications associated with total thyroidectomy, as well as the corrective measures to address complications. In addition, the influence of potential confounders affecting risk-recall, such as anxiety and pre-existing memory disturbance, are also examined. METHODS: Consecutive adult (≥18 years old) patients undergoing total thyroidectomy at a single academic tertiary care referral centre are included. Participants are randomly assigned into either the experimental group (with pamphlets) or the control group by a computerized randomization system (Clinstat). All participants filled out a Hospital Anxiety and Depression Scale (HADS) and they are tested by the physician for short-term memory loss using the Memory Impairment Screen (MIS) exam. All patients are evaluated at one week post-operatively. The written recall questionnaire test is also administered during this clinical encounter. RESULTS: Forty-nine patients are included--25 of them receive verbal consent only, while another 24 patients received both verbal consent and patient education information pamphlets. The overall average of correct answers for each group was 83% and 80% in the control and intervention groups, respectively, with no statistically significant differences. There are also no statistically significant differences between the two groups, in both interview duration, in time between interviews, and in recall tests. No correlation is also apparent between the pre-op HADS score and the recall questionnaire overall score. CONCLUSIONS: A pre-operative thyroid surgical information pamphlet alone might not be sufficient to enhance patient test scores and optimally educate the patient on their expected care pathway in thyroid surgery. Supplementation with alternative means of patient education perhaps using emerging technologies needs to be further investigated.

The Skin Cancer Objective Structured Clinical Examination (SCOSCE): A multi-institutional collaboration to develop and validate a clinical skills assessment for melanoma.

BACKGROUND: Assessing medical students on core skills related to melanoma detection is challenging in the absence of a well-developed instrument. OBJECTIVE: We sought to develop an objective structured clinical examination for the detection and evaluation of melanoma among medical students. METHODS: This was a prospective cohort analysis of student and objective rater agreement on performance of clinical skills and assessment of differences in performance across 3 schools. RESULTS: Kappa coefficients indicated excellent agreement for 3 of 5 core skills including commenting on the presence of the moulage (k = 0.87, 95% confidence interval 0.77-0.96), obtaining a history for the moulage (k = 0.84, 95% confidence interval 0.74-0.94), and making a clinical impression (k = 0.80, 95% confidence interval 0.68-0.92). There were no differences in performance across schools with respect to 3 of 5 core skills: commenting on the presence of the moulage (P = .15), initiating a history (P = .53), and managing the suspicious lesion (P value range .07-.17). Overall, 54.2% and 44.7% of students commented on the presence of the moulage and achieved maximum performance of core skills, respectively, with no difference in performance across schools. LIMITATIONS: Limitations include overall sample size of students and schools. CONCLUSION: The Skin Cancer Objective Structured Clinical Examination represents a potentially important instrument to measure students' performance on the optimal step-by-step evaluation of a melanoma.

A common polymorphism in the 5' UTR of ERCC5 creates an upstream ORF that confers resistance to platinum-based chemotherapy.

We show that a common polymorphic variant in the ERCC5 5' untranslated region (UTR) generates an upstream ORF (uORF) that affects both the background expression of this protein and its ability to be synthesized following exposure to agents that cause bulky adduct DNA damage. Individuals that harbor uORF1 have a marked resistance to platinum-based agents, illustrated by the significantly reduced progression-free survival of pediatric ependymoma patients treated with such compounds. Importantly, inhibition of DNA-PKcs restores sensitivity to platinum-based compounds by preventing uORF1-dependent ERCC5 expression. Our data support a model in which a heritable 5' noncoding mRNA element influences individuals' responses to platinum-based chemotherapy.

Cap-Independent Translation in Hematological Malignancies.

Hematological malignancies are a heterogeneous group of diseases deriving from blood cells progenitors. Although many genes involved in blood cancers contain internal ribosome entry sites (IRESes), there has been only few studies focusing on the role of cap-independent translation in leukemia and lymphomas. Expression of IRES trans-acting factors can also be altered, and interestingly, BCL-ABL1 fusion protein expressed from "Philadelphia" chromosome, found in some types of leukemia, regulates several of them. A mechanism involving c-Myc IRES and cap-independent translation and leading to resistance to chemotherapy in multiple myeloma emphasize the contribution of cap-independent translation in blood cancers and the need for more work to be done to clarify the roles of known IRESes in pathology and response to chemotherapeutics.

Neutrophilic sebaceous adenitis with intralobular Demodex mites: a case report and review of the literature.

A 61-year-old white man presented with a 1-week history of an asymptomatic erythematous, annular plaque with minimal scale limited to the nasal bridge. Histological examination showed a mixed infiltrate of lymphocytes and neutrophils within sebaceous glands. The clinical and histopathological presentation was consistent with a diagnosis of neutrophilic sebaceous adenitis. Several Demodex brevis mites were present deep within the affected sebaceous lobules. Demodex brevis mites are uncommon inhabitants of sebaceous glands of the nose, presenting more commonly on other body sites. The cause of neutrophilic sebaceous adenitis is unknown, but the presence of D. brevis in affected sebaceous glands in this case suggests a possible association.