CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses.

Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3ß loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells.

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.

Nasal Delivery of Haemophilus haemolyticus Is Safe, Reduces Influenza Severity, and Prevents Development of Otitis Media in Mice.

BACKGROUND: Despite vaccination, influenza and otitis media (OM) remain leading causes of illness. We previously found that the human respiratory commensal Haemophilus haemolyticus prevents bacterial infection in vitro and that the related murine commensal Muribacter muris delays OM development in mice. The observation that M muris pretreatment reduced lung influenza titer and inflammation suggests that these bacteria could be exploited for protection against influenza/OM. METHODS: Safety and efficacy of intranasal H haemolyticus at 5 × 107 colony-forming units (CFU) was tested in female BALB/cARC mice using an influenza model and influenza-driven nontypeable Haemophilus influenzae (NTHi) OM model. Weight, symptoms, viral/bacterial levels, and immune responses were measured. RESULTS: Intranasal delivery of H haemolyticus was safe and reduced severity of influenza, with quicker recovery, reduced inflammation, and lower lung influenza virus titers (up to 8-fold decrease vs placebo; P ≤ .01). Haemophilus haemolyticus reduced NTHi colonization density (day 5 median NTHi CFU/mL = 1.79 × 103 in treatment group vs 4.04 × 104 in placebo, P = .041; day 7 median NTHi CFU/mL = 28.18 vs 1.03 × 104; P = .028) and prevented OM (17% OM in treatment group, 83% in placebo group; P = .015). CONCLUSIONS: Haemophilus haemolyticus has potential as a live biotherapeutic for prevention or early treatment of influenza and influenza-driven NTHi OM. Additional studies will deem whether these findings translate to humans and other respiratory infections.

SARS-CoV-2-specific T cells generated for adoptive immunotherapy are capable of recognizing multiple SARS-CoV-2 variants.

Adoptive T-cell immunotherapy has provided promising results in the treatment of viral complications in humans, particularly in the context of immunocompromised patients who have exhausted all other clinical options. The capacity to expand T cells from healthy immune individuals is providing a new approach to anti-viral immunotherapy, offering rapid off-the-shelf treatment with tailor-made human leukocyte antigen (HLA)-matched T cells. While most of this research has focused on the treatment of latent viral infections, emerging evidence that SARS-CoV-2-specific T cells play an important role in protection against COVID-19 suggests that the transfer of HLA-matched allogeneic off-the-shelf virus-specific T cells could provide a treatment option for patients with active COVID-19 or at risk of developing COVID-19. We initially screened 60 convalescent individuals and based on HLA typing and T-cell response profile, 12 individuals were selected for the development of a SARS-CoV-2-specific T-cell bank. We demonstrate that these T cells are specific for up to four SARS-CoV-2 antigens presented by a broad range of both HLA class I and class II alleles. These T cells show consistent functional and phenotypic properties, display cytotoxic potential against HLA-matched targets and can recognize HLA-matched cells infected with different SARS-CoV-2 variants. These observations demonstrate a robust approach for the production of SARS-CoV-2-specific T cells and provide the impetus for the development of a T-cell repository for clinical assessment.

Development and validation of Malaysian one stop crisis center service quality instrument (OSCC-Qual) for domestic violence management.

One Stop Crisis Center (OSCC) is a multi-sectorial center aimed to provide medical, social, legal, police and shelter services to survivors of domestic violence, rape, sexual assault, sodomy and child abuse. Although OSCCs have been established for almost three decades in different parts of the world including in Malaysia, there is a lack of a validated instrument to measure the service quality rendered in OSCCs. A validated instrument known as OSCC-Qual was developed using a 5-stage approach where (1) in stage 1, group discussions were conducted among all authors to identify potential items for the instrument; (2) in stage 2, content validation was performed by 13 experts using content validity index and modified kappa; (3) in stage 3, exploratory factor analysis was performed by 141 healthcare staff with experience in managing OSCC cases to validate the items as well as to identify the number of factors in the instrument; (4) in stage 4, confirmatory factor analysis was performed by 110 domestic violence survivors to ascertain the validity of the factors and items retained in stage 3 and (5) in stage 5, forward and backward translation into local Malay and Chinese languages was performed. Results: In stage 1, a total of 42 items were identified. No item was deleted in stage 2. In stage 3, a total of 7 factors (i.e., "information provision", "competency of staff", "professionalism", "supportive environment", "attitude of staff", "multi-sectorial coordination" and "tangibles") were identified. Four items were deleted due to poor factor loading. In stage 4, another 3 items were iteratively removed due to poor factor loading. Discriminant validity was good. Conclusion: With the availability of the 7-factor and 35-item OSCC-Qual instrument, it is hoped that the efficiency of OSCC in achieving its philosophical objectives after three decades of implementation can be unraveled and remedial actions can be taken, if necessary.

Evidence for motivational interviewing in educational settings among medical schools: a scoping review.

BACKGROUND: Motivational interviewing (MI) is a person-centred approach focused on empowering and motivating individuals for behavioural change. Medical students can utilize MI in patient education to engage with patients' chronic health ailments and maladaptive behaviours. A current scoping review was conducted to 1) determine the types of MI (conventional, adapted, brief and group MI) education programs in medical schools, delivery modalities and teaching methods used; 2) classify educational outcomes on the basis of Kirkpatrick's hierarchy; and 3) determine the key elements of MI education via the FRAMES (feedback, responsibility, advice, menu of options, empathy, self-efficacy) model. METHODS: This scoping review was conducted via the framework outlined by Arksey and O'Malley. Two online databases, CINAHL and MEDLINE Complete, were searched to identify MI interventions in medical education. Further articles were selected from bibliography lists and the Google Scholar search engine. RESULTS: From an initial yield of 2019 articles, 19 articles were included. First, there appears to be a bimodal distribution of most articles published between the two time periods of 2004--2008 and 2019--2023. Second, all the studies included in this review did not use conventional MI but instead utilized a variety of MI adaptation techniques. Third, most studies used face-to-face training in MI, whereas only one study used online delivery. Fourth, most studies have used a variety of interactive experiences to teach MI. Next, all studies reported outcomes at Kirkpatrick's Level 2, but only 4 studies reported outcomes at Kirkpatrick's Level 3. According to the FRAMES model, all studies (n=19; 100%) reported the elements of responsibility and advice. The element that was reported the least was self-efficacy (n = 12; 63.1%). CONCLUSION: Our findings suggest that motivational interviewing can be taught effectively in medical schools via adaptations to MI and a variety of teaching approaches. However, there is a need for further research investigating standardized MI training across medical schools, the adequate dose for training in MI and the implementation of reflective practices. Future studies may benefit from exploring and better understanding the relationship between MI and self-efficacy in their MI interventions.

GPR183 antagonism reduces macrophage infiltration in influenza and SARS-CoV-2 infection.

RATIONALE: Severe viral respiratory infections are often characterised by extensive myeloid cell infiltration and activation and persistent lung tissue injury. However, the immunological mechanisms driving excessive inflammation in the lung remain poorly understood. OBJECTIVES: To identify the mechanisms that drive immune cell recruitment in the lung during viral respiratory infections and identify novel drug targets to reduce inflammation and disease severity. METHODS: Preclinical murine models of influenza A virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Oxidised cholesterols and the oxysterol-sensing receptor GPR183 were identified as drivers of monocyte/macrophage infiltration to the lung during influenza A virus (IAV) and SARS-CoV-2 infection. Both IAV and SARS-CoV-2 infection upregulated the enzymes cholesterol 25-hydroxylase (CH25H) and cytochrome P450 family 7 subfamily member B1 (CYP7B1) in the lung, resulting in local production of the oxidised cholesterols 25-hydroxycholesterol (25-OHC) and 7α,25-dihydroxycholesterol (7α,25-OHC). Loss-of-function mutation of Gpr183 or treatment with a GPR183 antagonist reduced macrophage infiltration and inflammatory cytokine production in the lungs of IAV- or SARS-CoV-2-infected mice. The GPR183 antagonist significantly attenuated the severity of SARS-CoV-2 infection and viral loads. Analysis of single-cell RNA-sequencing data on bronchoalveolar lavage samples from healthy controls and COVID-19 patients with moderate and severe disease revealed that CH25H, CYP7B1 and GPR183 are significantly upregulated in macrophages during COVID-19. CONCLUSION: This study demonstrates that oxysterols drive inflammation in the lung via GPR183 and provides the first preclinical evidence for the therapeutic benefit of targeting GPR183 during severe viral respiratory infections.

Beyond the scars: a qualitative study on the experiences of mastectomy among young women with breast cancer in a country with crisis.

BACKGROUND: As breast cancer incidence rises among younger women, there is a knowledge gap regarding the emotional, physical, and social effects of mastectomy, specifically in a crisis-affected country such as Syria. This study aimed to explore these effects on young women with breast cancer in Syria, taking into consideration the cultural significance of a woman's breast as part of her feminine identity. METHODS: A qualitative design, using semi-structured in-depth interviews with 10 young women with breast cancer who underwent mastectomy, was conducted between June to December 2022. RESULTS: Thematic analysis was used to analyze the data, and five main themes were identified: (1) psychological and emotional well-being (altered self-esteem and femininity, impact on sexual life and relationships, psychological distress associated with mastectomy, mirror trauma and the need for psychological care); (2) body image and breast reconstruction (the dilemma over reconstruction decision, body image and clothing and lack of access to prosthetic information/services); (3) social and interpersonal factors (lack of marriage choices and society's view and stigma); (4) coping mechanisms with mastectomy effects (family support; faith in god almighty; comparing their situation to others and use of prosthetics) and (5) physical health and functioning (physical effects on mobility and function). CONCLUSION: Mastectomy has significant physical, emotional, and social consequences on young women with breast cancer, particularly in crisis-affected Syria where access to breast reconstruction is limited. It is crucial for healthcare professionals to understand these impacts, to raise awareness, encourage early detection, and promote less aggressive treatments to improve women's quality of life.

Perception of nudge interventions to mitigate medication errors risk in healthcare service delivery.

BACKGROUND: Conventional cognitive interventions to reduce medication errors have been found to be less effective as behavioural change does not always follow intention change. Nudge interventions, which subtly steer one's choices, have recently been introduced. METHODS: Conducted from February to May 2023, this study aimed to determine the relationships between perceived effectiveness and perceived ease of implementation of six nudge interventions to reduce medication errors, i.e., provider champion, provider's commitment, peer comparison, provider education, patient education and departmental feedback, and the moderating effects of seniority of job positions and clinical experience on nudge acceptability. Partial Least Square Structural Equation Modelling was used for data analysis. RESULTS AND DISCUSSION: All six nudge strategies had significant positive relationships between perceived effectiveness and acceptability. In three out of six interventions, perceived ease of implementation was shown to have positive relationships with perceived acceptability. Only seniority of job position had a significant moderating effect on perceived ease of implementation in peer comparison intervention. Interventions that personally involve senior doctors appeared to have higher predictive accuracy than those that do not, indicating that high power-distance culture influence intervention acceptability. CONCLUSION: For successful nudge implementations, both intrinsic properties of the interventions and the broader sociocultural context is necessary.

Tutorless board game as an alternative to tabletop exercise for disaster response training: perception of interaction engagement and behavioral intention.

BACKGROUND: Although tabletop exercise is a commonly used method for disaster response training, it is labor-intensive, requires a tutor for facilitation and may not be ideal in a pandemic situation. Board game is a low-cost and portable alternative that can be utilized for this purpose. The purpose of this study was to compare the perception of interaction engagement and behavioral intention to use a newly developed board game with tabletop exercise for disaster training. METHODS: Using the Mechanics-Dynamics-Aesthetics' (MDA) framework, a new, tutorless educational board game known as the Simulated Disaster Management And Response Triage training ("SMARTriage") was first developed for disaster response training. Subsequently, the perceptions of 113 final year medical students on the "SMARTriage" board game was compared with that of tabletop exercise using a crossover design. RESULTS: Using Wilcoxon signed rank test, it was that found that tabletop exercise was generally rated significantly higher (with p < 0.05) in terms of perceived usefulness, perceived ease of use and behavioral intention compared to tutorless "SMARTriage" board game. However, in terms of attitude and interaction engagement, there was no significant difference between these two learning methods for most of the items. CONCLUSION: Although a clear preference for tutorless board game was not demonstrated, this study suggests that board game was not inferior to tabletop exercise in fostering interaction engagement suggesting that "SMARTriage" board game could potentially be used as an adjunct for teaching and learning activities.

Selection on Phalanx Development in the Evolution of the Bird Wing.

The frameshift hypothesis is a widely accepted model of bird wing evolution. This hypothesis postulates a shift in positional values, or molecular-developmental identity, that caused a change in digit phenotype. The hypothesis synthesized developmental and paleontological data on wing digit homology. The "most anterior digit" (MAD) hypothesis presents an alternative view based on changes in transcriptional regulation in the limb. The molecular evidence for both hypotheses is that the MAD expresses Hoxd13 but not Hoxd11 and Hoxd12. This digit I "signature" is thought to characterize all amniotes. Here, we studied Hoxd expression patterns in a phylogenetic sample of 18 amniotes. Instead of a conserved molecular signature in digit I, we find wide variation of Hoxd11, Hoxd12, and Hoxd13 expression in digit I. Patterns of apoptosis, and Sox9 expression, a marker of the phalanx-forming region, suggest that phalanges were lost from wing digit IV because of early arrest of the phalanx-forming region followed by cell death. Finally, we show that multiple amniote lineages lost phalanges with no frameshift. Our findings suggest that the bird wing evolved by targeted loss of phalanges under selection. Consistent with our view, some recent phylogenies based on dinosaur fossils eliminate the need to postulate a frameshift in the first place. We suggest that the phenotype of the Archaeopteryx lithographica wing is also consistent with phalanx loss. More broadly, our results support a gradualist model of evolution based on tinkering with developmental gene expression.

The impact of influenza pulmonary infection and inflammation on vagal bronchopulmonary sensory neurons.

Influenza A virus (IAV) is rapidly detected in the airways by the immune system, with resident parenchymal cells and leukocytes orchestrating viral sensing and the induction of antiviral inflammatory responses. The airways are innervated by heterogeneous populations of vagal sensory neurons which also play an important role in pulmonary defense. How these neurons respond to IAV respiratory infection remains unclear. Here, we use a murine model to provide the first evidence that vagal sensory neurons undergo significant transcriptional changes following a respiratory IAV infection. RNA sequencing on vagal sensory ganglia showed that IAV infection induced the expression of many genes associated with an antiviral and pro-inflammatory response and this was accompanied by a significant increase in inflammatory cell recruitment into the vagal ganglia. Assessment of gene expression in single-vagal sensory neurons confirmed that IAV infection induced a neuronal inflammatory phenotype, which was most prominent in bronchopulmonary neurons, and also evident in some neurons innervating other organs. The altered transcriptome could be mimicked by intranasal treatment with cytokines and the lung homogenates of infected mice, in the absence of infectious virus. These data argue that IAV pulmonary infection and subsequent inflammation induces vagal sensory ganglia neuroinflammation and this may have important implications for IAV-induced morbidity.

A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters.

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.

COVID-19 aerosol box as protection from droplet and aerosol contaminations in healthcare workers performing airway intubation: a randomised cross-over simulation study.

BACKGROUND: Concerns over high transmission risk of SARS-CoV-2 have led to innovation and usage of an aerosol box to protect healthcare workers during airway intubation in patients with COVID-19. Its efficacy as a barrier protection in addition to the use of a standard personal protective equipment (PPE) is not fully known. We performed a simulated study to investigate the relationship between aerosol box usage during intubation and contaminations on healthcare workers pre-doffing and post-doffing of PPE. METHODS: This was a randomised cross-over study conducted between 9 April to 5 May 2020 in the ED of University Malaya Medical Centre. Postgraduate Emergency Medicine trainees performed video laryngoscope-assisted intubation on an airway manikin with and without an aerosol box in a random order. Contamination was simulated by nebulised Glo Germ. Primary outcome was number of contaminated front and back body regions pre-doffing and post-doffing of PPE of the intubator and assistant. Secondary outcomes were intubation time, Cormack-Lehane score, number of intubation attempts and participants' feedback. RESULTS: Thirty-six trainees completed the study interventions. The number of contaminated front and back body regions pre-doffing of PPE was significantly higher without the aerosol box (all p values<0.001). However, there was no significant difference in the number of contaminations post-doffing of PPE between using and not using the aerosol box, with a median contamination of zero. Intubation time was longer with the aerosol box (42.5 s vs 35.5 s, p<0.001). Cormack-Lehane scores were similar with and without the aerosol box. First-pass intubation success rate was 94.4% and 100% with and without the aerosol box, respectively. More participants reported reduced mobility and visibility when intubating with the aerosol box. CONCLUSIONS: An aerosol box may significantly reduce exposure to contaminations but with increased intubation time and reduced operator's mobility and visibility. Furthermore, the difference in degree of contamination between using and not using an aerosol box could be offset by proper doffing of PPE.

A High-Fat Diet Increases Influenza A Virus-Associated Cardiovascular Damage.

BACKGROUND: Influenza A virus (IAV) causes a wide range of extrarespiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined. METHODS: Here, we sought to use transcriptional profiling, virology, histology, and echocardiograms to investigate the role of a high-fat diet in IAV-associated cardiac damage. RESULTS: Transcriptional profiling showed that, compared to their low-fat counterparts (LF mice), mice fed a high-fat diet (HF mice) had impairments in inflammatory signaling in the lung and heart after IAV infection. This was associated with increased viral titers in the heart, increased left ventricular mass, and thickening of the left ventricular wall in IAV-infected HF mice compared to both IAV-infected LF mice and uninfected HF mice. Retrospective analysis of clinical data revealed that cardiac complications were more common in patients with excess weight, an association which was significant in 2 out of 4 studies. CONCLUSIONS: Together, these data provide the first evidence that a high-fat diet may be a risk factor for the development of IAV-associated cardiovascular damage and emphasizes the need for further clinical research in this area.

A comparison between the effectiveness of a gamified approach with the conventional approach in point-of-care ultrasonographic training.

BACKGROUND: Although gamification increases user engagement, its effectiveness in point-of-care ultrasonographic training has yet to be fully established. This study was conducted with the primary outcome of evaluating its effectiveness in point-of-care ultrasonographic training as compared to conventional approach. METHODS: Participants consisting of junior doctors were randomized into either the (1) gamified or the (2) conventional educational approach for ultrasonographic training. RESULTS: A total of 31 junior doctors participated in this study (16 participants in gamified arm, 15 in the conventional arm after one participant from the conventional arm dropped out due to work commitment). Two-way mixed ANOVA test showed that there was no statistically significant interaction between the types of educational approach and time of testing (pre-test, post-test, 2 months post-training) for both theoretical knowledge score and practical skills score, with F(2, 58) = 39.6, p < 0.001, partial η2 = 0.4 and F(2, 58) = 3.06, p = 0.06, partial η2 = 0.095, respectively. For theoretical knowledge score, pairwise comparisons showed that the mean 2 months post-training scores (20.28 +/- 0.70, 95% CI 18.87-21.69) and mean post-test scores (20.27 +/- 0.65, 95% CI 18.94-21.60) were better than the pre-test scores (12.99 +/- 0.50, 95% CI 11.97-14.00) with p-values < 0.001 for both comparisons respectively. Similarly, for practical skill score, pairwise comparisons showed that the mean 2 months post-training scores (20.28 +/- 0.70, 95% CI 18.87-21.69) and mean post-test scores (20.27 +/- 0.65, 95% CI 18.94-21.60) were also better than the pre-test scores (12.99 +/- 0.50, 95% CI 11.97-14.00) with p-values < 0.001 for both comparisons respectively. Participants in the gamification arm generally perceived the various game elements and game mechanics as useful in contributing and motivating them to learn ultrasonography. CONCLUSIONS: Gamification approach could be an effective alternative to conventional approach in point-of-care ultrasonographic training.

Perception of the usability and implementation of a metacognitive mnemonic to check cognitive errors in clinical setting.

BACKGROUND: Establishing a diagnosis is a complex, iterative process involving patient data gathering, integration and interpretation. Premature closure is a fallacious cognitive tendency of closing the diagnostic process before sufficient data have been gathered. A proposed strategy to minimize premature closure is the use of a checklist to trigger metacognition (the process of monitoring one's own thinking). A number of studies have suggested the effectiveness of this strategy in classroom settings. This qualitative study examined the perception of usability of a metacognitive mnemonic checklist called TWED checklist (where the letter "T = Threat", "W = What if I am wrong? What else?", "E = Evidence" and "D = Dispositional influence") in a real clinical setting. METHOD: Two categories of participants, i.e., medical doctors (n = 11) and final year medical students (Group 1, n = 5; Group 2, n = 10) participated in four separate focus group discussions. Nielsen's 5 dimensions of usability (i.e. learnability, effectiveness, memorability, errors, and satisfaction) and Pentland's narrative network were adapted as the framework to study the usability and the implementation of the checklist in a real clinical setting respectively. RESULTS: Both categories (medical doctors and medical students) of participants found that the TWED checklist was easy to learn and effective in promoting metacognition. For medical student participants, items "T" and "W" were believed to be the two most useful aspects of the checklist, whereas for the doctor participants, it was item "D". Regarding its implementation, item "T" was applied iteratively, items "W" and "E" were applied when the outcomes did not turn out as expected, and item "D" was applied infrequently. The one checkpoint where all four items were applied was after the initial history taking and physical examination had been performed to generate the initial clinical impression. CONCLUSION: A metacognitive checklist aimed to check cognitive errors may be a useful tool that can be implemented in the real clinical setting.

Implementing blended learning in emergency airway management training: a randomized controlled trial.

BACKGROUND: While emergency airway management training is conventionally conducted via face-to-face learning (F2FL) workshops, there are inherent cost, time, place and manpower limitations in running such workshops. Blended learning (BL) refers to the systematic integration of online and face-to-face learning aimed to facilitate complex thinking skills and flexible participation at a reduced financial, time and manpower cost. This study was conducted to evaluate its effectiveness in emergency airway management training. METHODS: A single-center prospective randomised controlled trial involving 30 doctors from Sarawak General Hospital, Malaysia was conducted from September 2016 to February 2017 to compare the effectiveness of BL versus F2FL for emergency airway management training. Participants in the BL arm were given a period of 12 days to go through the online materials in a learning management system while those in the F2FL arm attended a-day of face-to-face lectures (8 h). Participants from both arms then attended a day of hands-on session consisting of simulation skills training with airway manikins. Pre- and post-tests in knowledge and practical skills were administered. E-learning experience and the perception towards BL among participants in the BL arm were also assessed. RESULTS: Significant improvements in post-test scores as compared to pre-test scores were noted for participants in both BL and F2FL arms for knowledge, practical, and total scores. The degree of increment between the BL group and the F2FL arms for all categories were not significantly different (total scores: 35 marks, inter-quartile range (IQR) 15.0 - 41.0 vs. 31 marks, IQR 24.0 - 41.0, p = 0.690; theory scores: 18 marks, IQR 9 - 24 vs. 19 marks, IQR 15 - 20, p = 0.992; practical scores: 11 marks, IQR 5 -18 vs. 10 marks, IQR 9 - 20, p = 0.461 respectively). The overall perception towards BL was positive. CONCLUSIONS: Blended learning is as effective as face-to-face learning for emergency airway management training of junior doctors, suggesting that blended learning may be a feasible alternative to face-to-face learning for such skill training in emergency departments. TRIAL REGISTRATION: Malaysian National Medical Research NMRR-16-696-30190 . Registered 28 April 2016.

Expression of STRA8 is conserved in therian mammals but expression of CYP26B1 differs between marsupials and mice.

The first sign of mammalian germ cell sexual differentiation is the initiation of meiosis in females and of mitotic arrest in males. In the mouse, retinoic acid induces ovarian Stra8 expression and entry of germ cells into meiosis. In developing mouse testes, cytochrome P450 family 26, subfamily b, polypeptide 1 (CYP26B1) produced by the Sertoli cells degrades retinoic acid, preventing Stimulated by Retinoic Acid Gene 8 (Stra8), expression and inhibiting meiosis. However, in developing humans, there is no evidence that CYP26B1 acts a meiosis-inhibiting factor. We therefore examined aspects of the retinoic acid/STRA8/CYP26B1 pathway during gonadal development in the tammar wallaby, a marsupial, to understand whether retinoic acid stimulation of STRA8 and CYP26B1 degradation of retinoic acid was conserved between widely divergent mammals. In tammar ovaries, as in human ovaries and unlike the pattern in mice, CYP26B1 expression was not downregulated before the onset of meiosis. Exposure of pre-meiotic tammar ovaries to exogenous retinoic acid in vitro upregulated STRA8 expression compared to controls. We conclude that retinoic acid and STRA8 are conserved factors that control the initiation of meiosis amongst mammals but the role of CYP26B1 as a meiosis-inhibiting factor may be specific to rodents. The identity of the marsupial meiosis-inhibiting factor remains unknown.

Motor hyperactivity of the iron-deficient rat - an animal model of restless legs syndrome.

BACKGROUND: Abnormal striatal dopamine transmission has been hypothesized to cause restless legs syndrome. Dopaminergic drugs are commonly used to treat restless legs syndrome. However, they cause adverse effects with long-term use. An animal model would allow the systematic testing of potential therapeutic drugs. A high prevalence of restless legs syndrome has been reported in iron-deficient anemic patients. We hypothesized that the iron-deficient animal would exhibit signs similar to those in restless legs syndrome patients. METHODS: After baseline polysomnographic recordings, iron-deficient rats received pramipexole injection. Then, iron-deficient rats were fed a standard rodent diet, and polysomnographic recording were performed for 2 days each week for 4 weeks. RESULTS: Iron-deficient rats have low hematocrit levels and show signs of restless legs syndrome: sleep fragmentation and periodic leg movements in wake and in slow-wave sleep. Iron-deficient rats had a positive response to pramipexole treatment. After the iron-deficient rats were fed the standard rodent diet, hematocrit returned to normal levels, and sleep quality improved, with increased average duration of wake and slow-wave sleep episodes. Periodic leg movements decreased during both waking and sleep. Hematocrit levels positively correlated with the average duration of episodes in wake and in slow-wave sleep and negatively correlated with periodic leg movements in wake and in sleep. Western blot analysis showed that striatal dopamine transporter levels were higher in iron-deficient rats. CONCLUSIONS: The iron-deficient rat is a useful animal model of iron-deficient anemic restless legs syndrome. © 2017 International Parkinson and Movement Disorder Society.