Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A mixed method, multiperspective evaluation of a near peer teaching programme

Purpose of study Peer teaching (PT) has become increasingly popular. PT may offer benefits for students, tutors and institutions. Although resistance to PT has been identified among faculty, research has typically focused on students' experiences and perceptions, rather than those of the peer tutors or senior doctors/medical faculty. The current study comprised of a comprehensive, multiperspective evaluation of a near PT programme delivered by interns to final-year medical students in the Republic of Ireland. Study design This study employed a mixed methods design, using both interviews and questionnaires to assess students' (n=130), interns' (n=49) and medical faculty's or senior doctors' (n=29) perceptions of the programme. Results All three groups were emphatic about the programme's benefits, although senior doctors and faculty reported significantly more positive attitudes than the others. Mean ratings of the programme's value, out of 10, were 8.2 among students, 8.2 among interns and 9.1 among senior doctors and faculty. Challenges identified were largely organisational in nature. Perceived benefits for students included the informality of teaching sessions, increased opportunities in the clinical environment and improvements in exam preparedness. Perceived benefits for the interns included improvements in knowledge and teaching ability and experience as a role model. Conclusions PT programmes have been posited as an ‘easy fix’ to growing numbers of students. However, it is apparent that PT has substantial value outside of this. Future research that conducts economic evaluations of such programmes and that collects objective data on teaching quality and student learning would be of much interest.This research was supported by the Health Service Executive's National Doctors Training and Planning.peer-reviewe

A mixed-methods examination of the nature and frequency of medical error among junior doctors

Abstract Purpose of the study To examine junior doctors’ experience and perceptions of medical errors in which they had been involved. Study design A mixed-methods design, consisting of an error survey and critical incident technique (CIT) interviews, was used. The survey asked doctors in the first year of postgraduate training in Ireland whether they had made a medical error that had ‘played on (their) mind’, and if so, to identify factors that had contributed to the error. The participants in the CIT interviews were asked to describe a medical error in which they had been involved. Results A total of 201 out of 332 (60.5%) respondents to the survey reported making an error that ‘played on their mind’. 'Individual factors’ were the most commonly identified group of factors (188/201; 93.5%), with ‘high workload’ (145/201; 72.1%) the most commonly identified contributory factor. Of the 28 CIT interviews which met the criteria for analysis, ‘situational factors’ (team, staff, task characteristics, and service user factors) were the most commonly identified group of contributory factors (24/28; 85.7%). A total of eight of the interviews were judged by subject matter experts (n=8) to be of medium risk to patients, and 20 to be of high-risk to patients. A significantly larger proportion of high-risk scenarios were attributed to ‘local working conditions’ than the medium-risk scenarios. Conclusions There is a need to prepare junior doctors to manage, and cope with, medical error and to ensure that healthcare professionals are adequately supported throughout their careers.This research was partially supported by funding from the National Doctor Training and Planning, Health Services Executive, Republic of Irelandpeer-reviewe

A mixed-methods examination of the nature and frequency of medical error among junior doctors

Abstract Purpose of the study To examine junior doctors’ experience and perceptions of medical errors in which they had been involved. Study design A mixed-methods design, consisting of an error survey and critical incident technique (CIT) interviews, was used. The survey asked doctors in the first year of postgraduate training in Ireland whether they had made a medical error that had ‘played on (their) mind’, and if so, to identify factors that had contributed to the error. The participants in the CIT interviews were asked to describe a medical error in which they had been involved. Results A total of 201 out of 332 (60.5%) respondents to the survey reported making an error that ‘played on their mind’. \u27Individual factors’ were the most commonly identified group of factors (188/201; 93.5%), with ‘high workload’ (145/201; 72.1%) the most commonly identified contributory factor. Of the 28 CIT interviews which met the criteria for analysis, ‘situational factors’ (team, staff, task characteristics, and service user factors) were the most commonly identified group of contributory factors (24/28; 85.7%). A total of eight of the interviews were judged by subject matter experts (n=8) to be of medium risk to patients, and 20 to be of high-risk to patients. A significantly larger proportion of high-risk scenarios were attributed to ‘local working conditions’ than the medium-risk scenarios. Conclusions There is a need to prepare junior doctors to manage, and cope with, medical error and to ensure that healthcare professionals are adequately supported throughout their careers.This research was partially supported by funding from the National Doctor Training and Planning, Health Services Executive, Republic of Irelan

Stress, coping, and psychological resilience among physicians

Abstract Background Recent research has demonstrated that burnout is widespread among physicians, and impacts their wellbeing, and that of patients. Such data have prompted efforts to teach resilience among physicians, but efforts are hampered by a lack of understanding of how physicians experience resilience and stress. This study aimed to contribute to knowledge regarding how physicians define resilience, the challenges posed by workplace stressors, and strategies which enable physicians to cope with these stressors. Methods A qualitative approach was adopted, with 68 semi-structured interviews conducted with Irish physicians. Data were analysed using deductive content-analysis. Results Five themes emerged from the interviews. The first theme, ‘The Nature of Resilience’ captured participants’ understanding of resilience. Many of the participants considered resilience to be “coping”, rather than “thriving” in instances of adversity. The second theme was ‘Challenges of the Profession’, as participants described workplace stressors which threatened their wellbeing, including long shifts, lack of resources, and heavy workloads. The third theme, ‘Job-related Gratification’, captured aspects of the workplace that support resilience, such as gratification from medical efficacy. ‘Resilience Strategies (Protective Practices)’ summarised coping behaviours that participants considered to be beneficial to their wellbeing, including spending time with family and friends, and the final theme, ‘Resilience Strategies (Attitudes)’, captured attitudes which protected against stress and burnout. Conclusions This study emphasised the need for further research the mechanisms of physician coping in the workplace and how we can capitalise on insights into physicians’ experiences of coping with system-level stressors to develop interventions to improve resilience