ATTR amyloidosis is a fatal disease associated with the accumulation of transthyretin (ATTR) fibrils that lead to organ failure and death. Mutations in the TTR gene or aging may accelerate the deposition of variant (ATTRv) or wild-type (ATTRwt) transthyretin, respectively. Although ATTR amyloidosis patients accumulate ATTR fibrils in virtually every organ, the clinical presentation is often unpredictable and variable. Recent studies in cryo-electron microscopy (cryo-EM) have revealed that in tauopathies and synucleinopathies, diseases involving amyloidosis of tau and α-synuclein, respectively, all the patients of the same disease display the same fibril fold, or polymorph. In this study, we use cryo-EM to explore whether fibrils from heart tissue of different patients with cardiac ATTR amyloidosis share a common fold. We determined the molecular structures of fibrils extracted from the hearts of seven patients, including both ATTRv and ATTRwt carriers, at resolutions of 3.0 to 3.7 Å. We found that ATTRv mutations perturb the fibril conformation whereas ATTRwt fibrils share a common structure fold. Our findings suggest that unlike in tauopathies and synucleinopathies, ATTRv fibrils display structural polymorphism driven by each individual and their genotypes. ATTR polymorphism challenges the current paradigm of ″one disease equals one fibril polymorph,″ and questions whether similarly novel conformations occur in other amyloidoses.

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We investigated the effect of head compression and acidaemia during labour in 25 African primigravidae. Evidence that head compression had occurred during labour was confirmed by both clinical and radiological means at the end of a trial of labour. No significant difference could be demonstrated in the quantity of fetal electroencephalogram (EEG) abnormality that occurred in the groups with marked head compression as compared to the groups without marked head compression. Deterioration in the fetal EEG to a flat record known as electrocerebral silence (ECS) was associated with the development of acidaemia. As fetal heart rate (FHR) decelerations appeared the percentage of ECS in the fetal EEG record increased significantly (P < 0.05), and likewise, as fetal acidaemia developed a highly significant increase in ECS in the fetal EEG was demonstrated (P < O*OOl). We concluded that in the management of trial of labour there was no significant deleterious change in the fetal EEG as a result of head compression, unless fetal acidaemia supervened. However, in the majority of these cases a significant increase in ECS to more than 20 per cent occurred in association with only moderate acidaemia (pH 7.25 to 7.30).CEPHALOPELVIC disproportion remains a major obstetrical hazard in developing countries and contributes significantly to perinatal death rates. In many cases disproportion and fetal asphyxia co-exist and make the exact cause of death difficult to determine. Perinatal statistics from Harare Hospital, Salisbury reveal that between 15 to 20 per cent of perinatal deaths are due to 269

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