A review of the clinical spectrum of BRAT1 disorders and case of developmental and epileptic encephalopathy surviving into adulthood.

Pathogenic variants in BRAT1 are associated with a spectrum of clinical syndromes ranging from Lethal Neonatal Rigidity and Multifocal Seizure syndrome (RMFSL) to Neurodevelopmental Disorder with Cerebellar Atrophy and with or without Seizures (NEDCAS). RMFSL is characterized by early-onset multifocal seizures with microcephaly. Death occurs during infancy although a less severe course with later onset seizures and longer survival into childhood has been described. Here, we summarize published cases of BRAT1 disorders and present the case of a 20-year-old man with two heterozygous BRAT1 variants and a relatively later age of seizure onset with survival into adulthood. This case expands the spectrum of disease associated with BRAT1 variants and highlights the utility of genetic testing to identify the cause of developmental and epileptic encephalopathies where clinical heterogeneity within a spectrum of disease exists.

Sympathetic neural activation does not mediate heart rate variability during repeated brief umbilical cord occlusions in near-term fetal sheep.

Changes in fetal heart rate variability (FHRV) and ST segment elevation (measured as the T/QRS ratio) are used to evaluate fetal adaptation to labour. The sympathetic nervous system (SNS) is an important contributor to FHRV under healthy normoxic conditions, and is critical for rapid support of blood pressure during brief labour-like asphyxia. However, although it has been assumed that SNS activity contributes to FHRV during labour; this has never been tested, and it is unclear whether the SNS contributes to the rapid increase in T/QRS ratio during brief asphyxia. Thirteen chronically instrumented fetal sheep at 0.85 of gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA; n = 6) or sham treatment (control; n = 7), followed 4-5 days later by 2 min episodes of complete umbilical cord occlusion repeated every 5 min for up to 4 h, or until mean arterial blood pressure fell to <20 mmHg for two successive occlusions. FHRV was decreased before occlusions in the 6-OHDA group (P < 0.05) and 2-4.5 h during recovery after occlusions (P < 0.05) compared to the control group. During each occlusion there was a rapid increase in T/QRS ratio. Between successive occlusions the T/QRS ratio rapidly returned to baseline, and FHRV increased above baseline in both groups (P < 0.05), with no significant effect of sympathectomy on FHRV or T/QRS ratio. In conclusion, these data show that SNS activity does not mediate the increase in FHRV between repeated episodes of brief umbilical cord occlusion or the transient increase in T/QRS ratio during occlusions.

Sustained sympathetic nervous system support of arterial blood pressure during repeated brief umbilical cord occlusions in near-term fetal sheep.

Sympathetic nervous system (SNS)-mediated peripheral vasoconstriction plays a key role in initial maintenance of blood pressure during rapid-onset asphyxia in the mammalian fetus, but it is attenuated after the first few minutes. It is unclear whether the SNS response is sustained during the brief, but frequently repeated, episodes of asphyxia characteristic of labor. In the present study, 14 fetal sheep at 0.85 of gestation received either chemical sympathectomy with 6-hydroxydopamine (6-OHDA; n = 7) or sham injection (control; n = 7), followed 4-5 days later by repeated 2-min episodes of complete umbilical cord occlusion every 5 min for up to 4 h or until mean arterial blood pressure (MAP) fell to <20 mmHg for two successive occlusions. In controls, umbilical cord occlusions were associated with a rapid initial fall in fetal heart rate (FHR) and femoral blood flow (FBF), with initial hypertension, followed by progressive development of hypotension during ongoing occlusions. Sympathectomy was associated with attenuation of the initial rise in MAP during umbilical cord occlusion, and after the onset of hypotension, a markedly more rapid fall of MAP to the nadir, with a correspondingly slower fall in FBF (P < 0.05). In contrast, MAP and FHR between successive occlusions were higher after sympathectomy (P < 0.05). There was no significant difference in the number of occlusions before terminal hypotension (6-OHDA; 16.1 ± 2.2 vs. control; 18.7 ± 2.3). These data show that SNS activity provides ongoing support for fetal MAP during prolonged exposure to brief repeated asphyxia.

Relationship between decile score of secondary school, the size of town of origin and career intentions of New Zealand medical students.

INTRODUCTION: New Zealand is facing a general practice workforce crisis, especially in rural communities. Medical school entrants from low decile schools or rural locations may be more likely to choose rural general practice as their career path. AIM: To determine whether a relationship exists between secondary school decile rating, the size of the town of origin of medical students and their subsequent medical career intentions. METHODS: University of Auckland medical students from 2006 to 2008 completed an entry questionnaire on a range of variables thought important in workforce determination. Analyses were performed on data from the 346 students who had attended a high school in New Zealand. RESULTS: There was a close relationship between size of town of origin and decile of secondary school. Most students expressed interests in a wide range of careers, with students from outside major cities making slightly fewer choices on average. DISCUSSION: There is no strong signal from these data that career specialty choices will be determined by decile of secondary school or size of town of origin. An increase in the proportion of rural students in medical programmes may increase the number of students from lower decile schools, without adding another affirmative action pathway.

In search of professionalism: implications for medical education.

This is the seventh article in an education series, discussing some of the 'hot topics' in teaching and learning in medicine. Historically, 'professionalism' was defined by the social structures of medicine, but has moved on to represent the expected behaviours and attributes of practitioners. Well publicised cases of professional misconduct, the rise of medical ethics as a discipline, and the move to a more patient-centred approach have driven the profile of professionalism into mainstream medical education. While there are many definitions of medical professionalism, there is a growing degree of consensus around what it encompasses; the way we manage tasks, our interactions with others, and looking after ourselves. The literature indicates that professionalism can be taught, learnt and applied; that attributes and behaviours can be identified; and that assessment is best approached using a range of methods over time. For learners, one of the critical factors in developing professionalism is the modelling by senior members of the profession as students move from peripheral observers to legitimate participants. Medical programmes in New Zealand are engaging with this literature in developing current curricula.