Background: Angiotensin converting enzyme 2 (ACE2) protein serves as the host receptor for SARS-CoV-2, with a critical role in viral infection. We aim to understand population level variation of nasopharyngeal ACE2 transcription in people tested for COVID-19 and the relationship between ACE2 transcription and SARS-CoV-2 viral load, while adjusting for expression of: (i) the complementary protease, Transmembrane serine protease 2 (TMPRSS2), (ii) soluble ACE2, (iii) age, and (iv) biological sex. The ACE2 gene was targeted to measure expression of transmembrane and soluble transcripts. Methods: A cross-sectional study of n = 424 "participants" aged 1À104 years referred for COVID-19 testing was performed in British Columbia, Canada. Patients who tested positive for COVID-19 were matched by age and biological sex to patients who tested negative. Viral load and host gene expression were assessed by quantitative reverse-transcriptase polymerase chain reaction. Bivariate analysis and multiple linear regression were performed to understand the role of nasopharyngeal ACE2 expression in SARS-CoV-2 infection. Findings: Analysis showed no association between age and nasopharyngeal ACE2 transcription in those who tested negative for COVID-19 (P = 0092). Mean relative transcription of transmembrane (P = 000012) and soluble (P<00001) ACE2 isoforms, as well as TMPRSS2 (P<00001) was higher in COVID-19-negative participants than COVID-19 positive ones, yielding a negative correlation between targeted host gene expression and positive COVID-19 diagnosis. In bivariate analysis of COVID-19-positive participants, transcription of transmembrane ACE2 positively correlated with SARS-CoV-2 viral RNA load (B = 049, R 2 =014, P<00001), transcription of soluble ACE2 negatively correlated (B= -085, R 2 = 026, P<00001), and no correlation was found with TMPRSS2 transcription (B= -0042, R 2 =<010, P = 069). Multivariable analysis showed that the greatest viral RNA loads were observed in participants with high transmembrane ACE2 transcription (B= 089, 95%CI: [059 to 118]), while transcription of the soluble isoform appears to protect against high viral RNA load in the upper respiratory tract (B= -0099, 95%CI: [-018 to -0022]). Interpretation: Nasopharyngeal ACE2 transcription plays a dual, contrasting role in SARS-CoV-2 infection of the upper respiratory tract. Transcription of the transmembrane ACE2 isoform positively correlates, while transcription of the soluble isoform negatively correlates with viral RNA load after adjusting for age, biological sex, and transcription of TMPRSS2. Funding: This project (COV-55) was funded by Genome British Columbia as part of their COVID-19 rapid response initiative.

Most MD/PhD programme graduates remain significantly involved in research, but this involvement often does not correspond to traditional physician-scientist roles, in which a majority of time is dedicated to research. To minimise loss of investment in physician-scientist training, MD/PhD programmes should prioritise research productivity during training and the pursuit of additional research training during residency, and policymakers should establish stable sources of funding to reduce debt among graduates. Our data suggest further study is warranted to identify interventions to reduce attrition among female MD/PhD programme graduates.

Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. We establish the true incidence of neurogenic shock by comparing the most common clinical definitions used to diagnose the condition. Further, we characterize the acute progression and recovery of neurogenic shock. Daily blood pressure, heart rate, and fluid management as well as vasopressor therapy and neurologic status were collected over 30 days from 84 adults admitted to our tertiary trauma center after cervical (n = 56) and thoracic (n = 28) SCI. We found that the reported incidence of neurogenic shock varied greatly depending on which clinical definition was applied. By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.

IntroductionAn increase in crystal methamphetamine (methamphetamine) use during the overdose epidemic is being observed in British Columbia (BC), Canada, and across North America. Concurrent use (ie, using uppers and downers one after the other or together) can increase the risk of fatal and non-fatal opioid overdose.ObjectivesWe investigated motivations for concurrent use of uppers and downers, specifically how (eg, in what order) and why people use concurrently, to identify potential interventions to prevent overdose and other harms.Setting and participantsThe 2019 Harm Reduction Client Survey was administered across 22 harm reduction supply distribution sites in BC (n=621). This thematic analysis examined 307 responses by people who affirmed concurrent use to classify order and reasons for using uppers and downers concurrently.ResultsOf the 307 people who responded ‘yes’ to concurrent use, 179 (58.3%) used downers then uppers, 76 (24.8%) used uppers then downers and 184 (59.9%) mixed uppers and downers together. Four main reasons for concurrent use emerged: self-medication, availability and preference, drug effects/properties, and financial and life situation. People who mixed drugs together predominantly wanted to achieve desired drug effects/properties, such as a specific high or balancing stimulating and sedating effects.ConclusionsThe ongoing rise in overdoses in BC is multifactorial, and the recent parallel increases in methamphetamine use and concurrent use with opioids may contribute. Qualitative interviews may further elucidate reasons for concurrent use. Addressing reasons for concurrent use identified in this study through harm reduction strategies and education may affect the rates of overdose morbidity and mortality.

Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.