Rugby and cervical spine injuries – has anything changed? A 5-year review in the Western Cape

Objectives. To review the incidence of all rugby-associated cervical spine injuries in the Western Cape and identify risk factors.Methods. We reviewed case notes and X-rays of 27 male patients with rugby-related cervical spine injuries treated at the acute spinal injury (ASCI) unit at Groote Schuur Hospital from April 2003 to June 2008, and followed up with telephone interviews. Patient profile, rugby profile, subsequent injury management from the field to definitive surgery andneurological status on admission, discharge and followup using the American Spinal Injury Association (ASIA) classification were assessed.Results. Average patient age was 25.3 years; 19% of them were scholars. The highest level of education among the adults was primary school in 70% of cases. Forwards and backs had the same injury rate. Most injuries occurred outside the metropole; more occurred in the tackling phase; 39% occurred during foul play; a third of players were not stabilised with a collar on the field; and 65% were taken to an inappropriate primary contact centre. A median of 10 hours elapsed before admission to the ASCI unit. Facet dislocations occurred in59%; 8 presented neurologically complete and remained so; and 3 presented with residual sensation, with 2 improving to normal. Three presented as ASIA C improving to D, and all Ds improved to Es. Despite their injuries, 60% said they would advise their sons to play rugby. Only 22% regretted playing.Conclusions. Despite a reduction in cervical spine injuries in rugby in the Western Cape, the latter mostly occur outside the metropole, where levels of education are lower, foul play is more often associated with the injury, and rapid access to medical care is generally unavailabe

Expression and localization of NUB1 in Tauopathy and Alzheimer’s disease models

Alzheimer’s disease (AD) is characterized at a subcellular level by intracellular neurofibrillary tangles (NFTs), aggregates of hyperphosphorylated Tau, and by senile plaques, extracellular aggregates of amyloid beta peptides. Previous data revealed that Nedd8 ultimate buster 1 (NUB1) plays a role in reducing the aggregation and phosphorylation of Tau in an in vitro model. To clarify the role of NUB1 in AD, the spatiotemporal expression and localization of NUB1 was analyzed in T301L, a mouse model for Tauopathy characterized by NFTs, and in TASTPM mice, characterized by early development of senile plaques. The analysis revealed no change in the level of NUB1 expression in T301L mice and a significant decrease at 12 months in TASTPM mice. In brain cryosections, NUB1 expression was detected in the hippocampus and entorhinal cortex. Subcellularly, NUB1 was localized predominantly in the neuronal nuclei, but also in neuronal processes. In both mouse models at 12 months, NUB1 signal was observed to co-localize with AT8 positive cytoplasmic aggregates. Moreover in TASTPM mice, a NUB1 cytoplasmic signal was observed in non-neuronal cells. Our data confirm that NUB1 could be a therapeutic target in AD and also help to establish the appropriate window of opportunity for therapeutic intervention

The missing piece of the South Atlantic jigsaw: when continental break-up ignores crustal heterogeneity

Crustal heterogeneity is considered to play a critical role in the position of continental break-up, yet this can only be demonstrated when a fully constrained pre-break-up configuration of both conjugate margins is achievable. Limitations in our understanding of the pre-break-up crustal structure in the offshore region of many margins preclude this. In the southern South Atlantic, which is an archetypal conjugate margin, this can be achieved because of the high confidence in plate reconstruction. Prior to addressing the role of crustal heterogeneity, two questions have to be addressed: first, what is the location of the regionally extensive Gondwanan Orogeny that remains enigmatic in the Orange Basin, offshore South Africa; and, second, although it has been established that the Argentinian Colorado rift basin has an east–west trend perpendicular to the Orange Basin and Atlantic spreading, where is the western continuation of this east–west trend? We present here a revised structural model for the southern South Atlantic by identifying the South African fold belt offshore. The fold belt trend changes from north–south to east–west offshore and correlates directly with the restored Colorado Basin. The Colorado–Orange rifts form a tripartite system with the Namibian Gariep Belt, which we call the Garies Triple Junction. All three rift branches were active during the break-up of Gondwana, but during the Atlantic rift phase the Colorado Basin failed while the other two branches continued to rift, defining the present day location of the South Atlantic. In addressing these two outstanding questions, this study challenges the premise that crustal heterogeneity controls the position of continental break-up because seafloor spreading demonstrably cross-cuts the pre-existing crustal heterogeneity. Furthermore, we highlight the importance of differentiating between early rift evolution and subsequent rifting that occurs immediately prior to seafloor spreading

Negative Regulator of Ubiquitin-Like Protein 1 modulates the autophagy-lysosomal pathway via p62 to facilitate the extracellular release of tau following proteasome impairment

Negative regulator of ubiquitin-like protein 1 (NUB1) and its longer isoform NUB1L are ubiquitin-like (UBL)/ubiquitin-associated (UBA) proteins that facilitate the targeting of proteasomal substrates, including tau, synphilin-1 and huntingtin. Previous data revealed that NUB1 also mediated a reduction in tau phosphorylation and aggregation following proteasome inhibition, suggesting a switch in NUB1 function from targeted proteasomal degradation to a role in autophagy. Here, we delineate the mechanisms of this switch and show that NUB1 interacted specifically with p62 and induced an increase in p62 levels in a manner facilitated by inhibition of the proteasome. NUB1 moreover increased autophagosomes and the recruitment of lysosomes to aggresomes following proteasome inhibition. Autophagy flux assays revealed that NUB1 affected the autophagy–lysosomal pathway primarily via the UBA domain. NUB1 localized to cytosolic inclusions with pathological forms of tau, as well as LAMP1 and p62 in the hippocampal neurons of tauopathy mice. Finally, NUB1 facilitated the extracellular release of tau following proteasome inhibition. This study thus shows that NUB1 plays a role in regulating the autophagy–lysosomal pathway when the ubiquitin proteasome system is compromised, thus contributing to the mechanisms targeting the removal of aggregation-prone proteins upon proteasomal impairment

Books

Progress in Medical Virology. Vol. 39. Ed. by J. L. Melnick. Pp. x + 270. Illustrated. £115,70. Basel: S Karger. 1992.Assisted reproduction Micromanipulation of Human Gametes and Embryos. By J. Cohen, H. E. Malter, Beth E. Talansky and J. Grifo. pp. ix + 325. Illustrated. $111,50. New York: Raven Press. 1992.Congenital rubella syndrome EpideIDio1ogy and Infection. Vo!. 107 No. 1. Ed. by J. R. Partison, D. Baxby, J. G. Cruickshank, C. R. Madeley and W. C. Noble. Pp. viii + 239. Illustrated. £25. Cambridge: Cambridge University Press. 1991.Rural and urban hospitals The Hospital in Rural and Urban Districts: Report of a WHO Study Group on the Function of Hospitals at the First Referral Level. pp. vii + 74. SFr.120. Geneva: World Health Organisation. 1992.Perinatology Perinato1ogy: Nestle Nutrition Workshop Series. Vol. 26. Ed. by Erich Saling. pp. xiii + 194. illustrated.$69. New York: Raven Press. 1992.Anaesthetists Five Decades: The South African Society· of Anaesthetists 1943 - 1993. By Nagin Parbhoo. 330 pages and 70 phoros and illustrations. Published by the South African Society of Anaesthetists. Printed by National Book Printers.

Books

Brain work Brain Work and Mental Activity: Quantitative Studies with Radioactive Tracers. Ed. by N. A. Lassen, D. H. Ingvar, M. E. RaicWe and L. Friberg. Pp. 446. Illustrated. Copenhagen: Munksgaard. 1991.Neuroanatomy Neuroanatomy for Medical Students. 2nd ed. By ]. L. Wilkinson. pp. x + 307. illustrated. Oxford: Butterworth Heinemann. 1992.Atherosclerosis Molecular Biology of Atherosclerosis: Proceedings of the 57th European Atherosclerosis Society Meeting. Ed. by M. J. Halpern. Pp. xv + 662. Illustrated. £45. London: John libbey. 1992.Antibiotics Antibiotic Guidelines. By H. J. Koomhof and L. D. Liebowitz. pp. 122. Pretoria: JL van Schaik. 1991.Reproductive medicine Reproduction, Growth and Development. By A. Negro-Vilar and G. perez-Palacios. Pp. xv + 440. illustrated. $162,50. New York: Raven Press. 1991.Obesity research Progress in Obesity Research 1990. Ed. by Y. Oomura, S. Tarui, S. Inoue and T. Shimazu. Pp. xiii + 688. illustrated. £17,50. London: John Libbey. 1991.Epidemiology Fetal and Infant Origins of Adult Disease. Ed. by D.}. P. Barker. Pp. xv + 343. £30. London: BM}. 1992

Injured pedestrians in Cape Town - the role of alcohol

Objective. To establish a profile of injured adult pedestrians and attempt to define the role which alcohol plays in this regard. Design. Prospective survey of injured pedestrians whopresented consecutively over 9 weeks to Groote Schuur Hospital. Data on fatally injured pedestrians were retrospectively collected from the State Mortuary. Setting. Hospital-based study conducted at the trauma unit, Groote Schuur Hospital. Participants. A total of 321 pedestrians - 196 injured and 35 'dead on arrival'. Main outcome measures. Sociodemographics, blood alcohol concentration (BAC) and injury severity. Results. Patients were predominantly male and, on average, 35.6 years old. They were most frequently injured at night and over weekends. The BAC was positive in 62.1 % of pedestrians, and the mean BAC was 0.19 g/dl. Most pedestrians had at least one lower limb injury and nearly half had a head injury; however, BAC-positive pedestrians were 2.6 times more likely to have a head injury (P = 0.0009). Furthennore, BAC-positive pedestrians sustained more severe injuries, more frequently required admission to the ICU, had longer hospital admissions and were more likely to die of their injuries. The overall case fatality rate was 19.5%. Conclusions. The influence of alcohol intoxication among injured adult pedestrians in Cape Town is high, suggesting that alcohol plays a major role in these accidents. Consequently, there should be some degree of culpability in those who cross t~e road while in an intoxicated state. However, equal attention should be given to safe and convenient crossing points, good lighting and education with regard to the wearing of reflective clothing after dark.S Atr Med J 1996; 86; 1103-1105

A successful lifestyle intervention model replicated in diverse clinical settings

Lifestyle interventions (LIs) can treat metabolic syndrome and prevent type 2 diabetes mellitus, but they remain underutilised in routine practice. In 2010, an LI model was created in a rural primary care practice and spread with few resources to four other rural practices. A retrospective chart review evaluated changes in health indicators in two practice environments by following 372 participants, mainly women (mean age 52  years). Participants had a mean body mass index of 37 kg/m2 at baseline and lost an average of 12% of their initial body weight as a result of the intervention. Among  participants at the first intervention site for whom cardiometabolic data were available, the prevalence of metabolic syndrome decreased from 58% at baseline to 19% at follow-up. Taken as a whole, our experience suggests that LIs are feasible and deliver meaningful results in routine primary care practice

Editorials

Trauma - today and tomorrowNeutron therapy - clinical considerationsDon Craib's legacyHealth informatic

CRISPR-Cas9 correction of a nonsense mutation in LCA5 rescues lebercilin expression and localization in human retinal organoids

Mutations in the lebercilin-encoding gene LCA5 cause one of the most severe forms of Leber congenital amaurosis, an early-onset retinal disease that results in severe visual impairment. Here, we report on the generation of a patient-specific cellular model to study LCA5-associated retinal disease. CRISPR-Cas9 technology was used to correct a homozygous nonsense variant in LCA5 (c.835C>T; p.Q279∗) in patient-derived induced pluripotent stem cells (iPSCs). The absence of off-target editing in gene-corrected (isogenic) control iPSCs was demonstrated by whole-genome sequencing. We differentiated the patient, gene-corrected, and unrelated control iPSCs into three-dimensional retina-like cells, so-called retinal organoids. We observed opsin and rhodopsin mislocalization to the outer nuclear layer in patient-derived but not in the gene-corrected or unrelated control organoids. We also confirmed the rescue of lebercilin expression and localization along the ciliary axoneme within the gene-corrected organoids. Here, we show the potential of combining precise single-nucleotide gene editing with the iPSC-derived retinal organoid system for the generation of a cellular model of early-onset retinal disease