Single-cell transcriptome identifies molecular subtype of autism spectrum disorder impacted by de novo loss-of-function variants regulating glial cells.

BACKGROUND: In recent years, several hundred autism spectrum disorder (ASD) implicated genes have been discovered impacting a wide range of molecular pathways. However, the molecular underpinning of ASD, particularly from the point of view of 'brain to behaviour' pathogenic mechanisms, remains largely unknown. METHODS: We undertook a study to investigate patterns of spatiotemporal and cell type expression of ASD-implicated genes by integrating large-scale brain single-cell transcriptomes (> million cells) and de novo loss-of-function (LOF) ASD variants (impacting 852 genes from 40,122 cases). RESULTS: We identified multiple single-cell clusters from three distinct developmental human brain regions (anterior cingulate cortex, middle temporal gyrus and primary visual cortex) that evidenced high evolutionary constraint through enrichment for brain critical exons and high pLI genes. These clusters also showed significant enrichment with ASD loss-of-function variant genes (p < 5.23 × 10-11) that are transcriptionally highly active in prenatal brain regions (visual cortex and dorsolateral prefrontal cortex). Mapping ASD de novo LOF variant genes into large-scale human and mouse brain single-cell transcriptome analysis demonstrate enrichment of such genes into neuronal subtypes and are also enriched for subtype of non-neuronal glial cell types (astrocyte, p < 6.40 × 10-11, oligodendrocyte, p < 1.31 × 10-09). CONCLUSION: Among the ASD genes enriched with pathogenic de novo LOF variants (i.e. KANK1, PLXNB1), a subgroup has restricted transcriptional regulation in non-neuronal cell types that are evolutionarily conserved. This association strongly suggests the involvement of subtype of non-neuronal glial cells in the pathogenesis of ASD and the need to explore other biological pathways for this disorder.

Introducing the 4Ps Model of Transitioning to Distance Learning: A convergent mixed methods study conducted during the COVID-19 pandemic.

Significant concern has been raised regarding the effect of COVID-19 on medical education. This study aimed to shed light on the distance learning experiences of medical students and their instructors at the Mohammed Bin Rashid University of Medicine and Health Sciences (MBRU) in Dubai, United Arab Emirates. A convergent mixed methods approach was utilized. Qualitative and quantitative data was collected using a survey of closed-ended followed by open-ended questions. The percentage of the total average of satisfaction among stakeholders was 76.4%. The qualitative analysis led to developing the 4Ps Model of Transitioning to Distance Learning, which encapsulates four interrelated themes. It would be helpful to leverage the lessons learned to tailor blended medical programs with a reasonable mélange of experiences. The study also contributes to the mixed methods research by showcasing a means of adapting it to evaluate critical situations reliably and rapidly.

Challenges of Establishing a de novo Consultation-Liaison Psychiatry Service in a Tertiary Hospital: Practical considerations and challenges.

Consultation-liaison psychiatry (CLP), also known as psychosomatic medicine, is a subspecialty of psychiatry that focuses on the care of patients with mental health disorders and general medical/surgical conditions. Integrating CLP services facilitates diagnosis and management of patients with complex comorbidities. This article aimed to report the practical considerations and challenges associated with establishing a de novo CLP service in a tertiary hospital in the Gulf region. This includes discussing the rationale and clinical and educational benefits as well as the resources required for establishing a CLP service.

Perceptions and Attitudes of First-Year Medical Students on a Modified Team-Based Learning (TBL) Strategy in Anatomy.

OBJECTIVES: Although team-based learning (TBL) is widely used in medical education, its evaluation from the perspectives of the students exposed to it has been limited. This paper reports on a quantitative and qualitative evaluation of perceptions of first year medical students towards TBL. METHODS: Lectures in an anatomy course were transformed into a series of TBL sessions for two cohorts of first-year medical students. Each session consisted of pre-class reading, in-class readiness assurance tests, and problem-solving of clinical cases by student teams. At the end of each course, students were surveyed using qualitative and quantitative instruments to assess their perceptions of the strategy. Internal consistency of questionnaire items was determined by a reliability analysis (Cronbach's alpha). Principal component factor analysis and correspondence analysis were conducted on the quantitative data. Open-ended questions were explored by thematic analysis. RESULTS: Students' evaluations indicated that TBL is a welcome alternative to lecture-based teaching; as implemented in this study, it encouraged clinical problem solving and fruitful in-class discussion. Principal component factor analysis identified five factors (Cronbach's alpha 0.602-0.875). However, the majority of students disapproved of mixed gender TBL teams. Most students agreed that the strategy facilitated consistency in their study, generated an increased awareness about self-directed learning, and had a positive impact on their learning attitudes. CONCLUSION: TBL is a welcome instructional strategy as reported by our first-year medical students. It was perceived to be a better approach compared to content-based lectures. The effect on actual student performance is currently being investigated.

Implementing a modified team-based learning strategy in the first phase of an outcome-based curriculum--challenges and prospects.

BACKGROUND: Team-based learning (TBL) is an innovative form of collaborative learning. The aim of TBL is to create a motivational context in which students become accountable for their learning. AIM: Student attendance at didactic lecture sessions in our school is usually poor. A modified TBL approach in lieu of lectures was undertaken for the first time in a large class (150 students). This communication reports on the challenges of its implementation in our setting and preliminary data on its effects on student performance. METHOD: Using computer-based evaluation followed by an in-class activity, a modified TBL approach was implemented over two semesters during an introductory basic science course. Data on student performance, student motivation and faculty reflection were collected and analysed. RESULTS: This strategy had significantly enhanced students' class attendance. They performed better on the built-in TBL assessment (IRAT) compared to standard in-course tests. Besides content mastery, TBL approach could also instill useful attitudinal outcomes such as self-directed learning. CONCLUSIONS: The TBL strategy is a viable and refreshing alternative to the usual didactic faculty engagement with the teaching process. Students appear to do better in tests built-in within TBL as compared to stand-alone in-course tests.

"Between a Rock and a Hard Place": The discordant views among medical teachers about anatomy content in the undergraduate medical curriculum.

The last two decades of medical education have been marked by a persistent push towards curricular reform. Anatomy as a discipline, the unshakable foundation of medical teaching for hundreds of years, has been at the centre of this development. Although it is widely agreed that for doctors to be competent, they need an adequate knowledge of anatomy underpinning medicine, there is much less agreement over the quantity required, and who should decide and define it. Many clinicians feel medical students are being under-trained in this basic medical science before reaching the clinical stages. Professional accreditation boards advocate the reduction of factual information in undergraduate medical courses. Anatomists complain of a progressive erosion of the time allocated to the subject. Caught in the midst of this controversy is the student of anatomy who is left bewildered and confused about what is required from him to become a safe and competent health professional. The way forward might, first, be for medical schools to facilitate discussions between students, anatomy professors, and clinicians to bring these divergent perspectives into alignment. Second, the anatomists need to re-invent themselves in two principal frameworks: first, to present the subject in the context within which it will be utilised by the student, and second to employ the overwhelming learning tool of today, i.e. technology, in their teaching and assessment of the subject.

Interprofessional Education (IPE) Activity amongst Health Sciences Students at Sultan Qaboos University: The time is now!

Historically, health professionals have been educated in profession-specific institutions which provide limited opportunities for learning interprofessional (IP) skills. Many qualified practitioners are therefore poorly prepared for the challenges of IP practice (IPP). Patients today have complex needs and typically require more than one professional to address their medical issues and effective IP care relies upon health care professionals' abilities to communicate with one another. Competent communication improves the quality of care, thus enhancing patient outcomes. The objective of IP education (IPE) is to prepare students to deliver IP care in the future. Sultan Qaboos University's medical and nursing colleges train the future health workforce for Oman. However, students have no opportunities for collaborative learning. It is imperative that opportunities be created where students learn with, about, and from each other with the aim of improving the quality of care they are likely to deliver in the future.

Perceptions and Attitudes of Medical Students towards Two Methods of Assessing Practical Anatomy Knowledge.

OBJECTIVES: Traditionally, summative practical examination in anatomy takes the form of 'spotters' consisting of a stream of prosections, radiological images and dissections with pins indicating specific structures. Recently, we have started to administer similar examinations online using the quiz facility in Moodle™ (a free, open-source web application for producing modular internet-based courses) in addition to the traditional format. This paper reports on an investigation into students' perceptions of each assessment environment. METHODS: Over a 3-year period, practical assessment in anatomy was conducted either in traditional format or online via learning management software called Moodle™. All students exposed to the two examination formats at the College of Medicine & Health Sciences, Sultan Qaboos University, Oman, were divided into two categories: junior (Year 3) and senior (Year 4). An evaluation of their perception of both examination formats was conducted using a self-administered questionnaire consisting of restricted and free response items. RESULTS: More than half of all students expressed a clear preference for the online environment and believed it was more exam-friendly. This preference was higher amongst senior students. Compared to females, male students preferred the online environment. Senior students were less likely to study on cadavers when the examination was conducted online. Specimen quality, ability to manage time, and seating arrangements were major advantages identified by students who preferred the online format. CONCLUSION: Computer-based practical examinations in anatomy appeared to be generally popular with our students. The students adopted a different approach to study when the exam was conducted online as compared to the traditional 'steeplechase' format.

Eutopic endometrium from women with endometriosis shows altered ultrastructure and glycosylation compared to that from healthy controls--a pilot observational study.

Endometrial curettings from a cohort of 24 women with endometriosis were compared with matched biopsies from 14 healthy, fertile women and examined for ultrastructural changes and the secretion of glycans bound by the lectin from Dolichos biflorus. Ultrastructural analysis of glandular endometrial tissue from women with stages I to III endometriosis showed heterogeneous responses to the disease, biopsies often showing a mixture of features, combining delays in the maturation sequence with characteristics of later phenotypes particularly in the mid-late secretory phase of the menstrual cycle. Expression of glycans bound by Dolichos biflorus agglutinin was very variable in these cases but generally matched the observed ultrastructure. Biopsies from women with stage IV endometriosis showed immature gland morphology later in the cycle and also failed to express Dolichos biflorus agglutinin-binding glycans, suggesting an association between histological and biochemical function in advanced disease states. These findings may explain in part endometriosis-associated subfertility as blastocyst attachment is intimately associated with appropriate glycosylation and gland morphology.

Diesel exhaust particles in blood trigger systemic and pulmonary morphological alterations.

Short-term exposure to elevated levels of particulate matter is associated with increased respiratory and cardiovascular mortality and morbidity. However, the mechanisms underlying these effects are still unclear. Recent studies have suggested that inhaled ultrafine particles are able to translocate into the bloodstream. To gain more insight into this potential mechanism, we studied the effect of diesel exhaust particles (DEP, 0.02 and 0.1mg/kg), 48h following their intravenous administration, on systemic inflammation and both pulmonary and cardiac morphological alterations in rats. The intravenous administration of DEP (0.1mg/kg) triggered systemic inflammation characterized by an increase of monocyte and granulocyte numbers. Both doses of DEP caused a reduction of the number of red blood cells (RBC) and haemoglobin concentration. Transmission electron microscopy analysis of RBC after in vitro incubation (5microg/ml) or in vivo administration of DEP, revealed the presence of ultrafine-sized aggregates of DEP within the RBC. Larger aggregates were also taken up by the RBC. Moreover, while the myocardial morphology and capillary bed were not affected by DEP exposure, the lungs of rats exposed to DEP (0.02 and 0.1mg/kg) showed clear evidence of inflammation, characterized by neutrophils infiltration. Stereological analysis revealed an increase in interalveolar wall thickness and a decrease in numbers of alveolar sacs per unit area of lung parenchyma of rat exposed to DEP. We conclude that 48h after their systemic administration, DEP cause systemic and pulmonary morphological alterations.

Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat.

OBJECTIVES: To investigate whether combined treatment with lisinopril, an angiotensin-converting enzyme (ACE) inhibitor and exercise training would have an additive effect in enhancing the capillary supply of the left ventricular (LV) myocardium in spontaneously hypertensive rats (SHR). DESIGN: Twelve-week-old male SHR were divided into four groups (10-12 each): sedentary, sedentary treated with lisinopril (15-20 mg/kg per day by gavage), exercise trained, and exercise trained while treated with lisinopril. Exercise training consisted of 1 h a day/5 days a week of running on a treadmill. METHODS: After 10 weeks of experimental protocols, capillary surface density and length density were sterologically determined in 1 mum thick LV tissue samples from perfuse-fixed hearts. RESULTS: Lisinopril significantly reduced systolic blood pressure (SBP) and LV mass in the sedentary with lisinopril and exercise trained with lisinopril groups but did not affect the heart rate (HR). Exercise training did not reduce SBP or LV mass, but significantly reduced HR in the exercise trained and exercise trained with lisinopril groups. Lisinopril treatment (sedentary with lisinopril), exercise training (exercise) and their combination (exercise trained with lisinopril) significantly increased myocardial capillary surface area density by 26, 38 and 65% and length density by 38, 48 and 67%, respectively. CONCLUSION: Lisinopril administration and exercise training independently enhanced myocardial capillarization through a reduction of myocardial mass and stimulation of angiogenesis, respectively. A combination of the two treatments enhanced myocardial capillarization more than either intervention alone. This may aid in the restoration of the normal nutritional status of cardiac myocytes compromised by the hypertrophic state of hypertension.