A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.

Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina.

There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and the route of surgical delivery-intravitreal or subretinal. This study compared three of the most efficacious AAV vectors known to date in a mouse model of retinal degeneration (rd1 mouse) and macaque and human retinal explants. Green fluorescent protein (GFP) driven by a ubiquitous promoter was packaged into three AAV capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) and AAV2/2(7m8). Overall, AAV2/2(7m8) transduced the largest area of retina and resulted in the highest level of GFP expression, followed by AAV2/2(quad Y-F) and AAV2/8(Y733F). AAV2/2(7m8) and AAV2/2(quad Y-F) both resulted in similar patterns of transduction whether they were injected intravitreally or subretinally. AAV2/8(Y733F) transduced a significantly smaller area of retina when injected intravitreally compared with subretinally. Retinal ganglion cells, horizontal cells and retinal pigment epithelium expressed relatively high levels of GFP in the mouse retina, whereas amacrine cells expressed low levels of GFP and bipolar cells were infrequently transduced. Cone cells were the most frequently transduced cell type in macaque retina explants, whereas Müller cells were the predominant transduced cell type in human retinal explants. Of the AAV serotypes tested, AAV2/2(7m8) was the most effective at transducing a range of cell types in degenerate mouse retina and macaque and human retinal explants.

Wound healing with medications for rheumatoid arthritis in hand surgery.

Introduction. Medications used to treat rheumatoid arthritis, such as corticosteroids, disease-modifying agents (DMARDs), and injectable biological agents (anti-TNFα), may have widespread effects on wound healing. In hand surgery, it is important to balance the risks of poor wound healing from continuing a medication against the risks of a flare of rheumatoid arthritis if a drug is temporarily discontinued. Materials and Methods. A United Kingdom (UK) group of 28 patients had metacarpophalangeal joint replacement surgery in 35 hands (140 wounds). All medication for rheumatoid arthritis was continued perioperatively, except for the injectable biological agents. Results. There were no instances of wound dehiscence or deep infection and only one episode of minor superficial infection. Conclusions. We conclude that provided care is taken to identify and treat any problems promptly, it is appropriate to continue most antirheumatoid medications in the perioperative period during hand surgery to reduce the risk of destabilising the patients' overall rheumatoid disease control.

Review of emergency department wound management in soft tissue trauma - is there a plan?

OBJECTIVE: To assess current acute wound management in English emergency departments. METHOD: All English emergency departments including minor injury units (n=207) were successfully contacted and a telephone questionnaire was completed. This considered wound treatment policy; management including cleansing, analgesia, dressing selection, suturing, referral patterns, medical photography and antibiotic use. RESULTS: There was a 100% response. Only 40% of departments had a wound treatment policy. Most had implemented staff training, however the nature and timing of this was variable. Wound cleansing was performed by all departments. Most administered analgesia. Suturing was selectively performed by all departments. There was great diversity regarding dressing selection. The most common reasons for referral to specialist units were the complexity of injury and cosmetically sensitive areas. Photographs were regularly taken in one third of units questioned. CONCLUSION: This study confirmed an absence of a standard protocol for early soft tissue wound management in the emergency department setting. Key areas that could be improved are dressing simplification, more defined referral criteria and introduction of standardised protocols with structured teaching programmes. We propose a simple approach to management of acute soft tissue wounds that can be applied to most situations. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

Beware frontotemporal dermoids - they may have intracranial extension: a case of a middle cranial fossa cyst.

Congenital orbitofacial dermoid cysts are epithelial lined structures of ectodermal origin that may be associated with sinus tracts and variable deep extension. Midline lesions may extend intracranially, while lateral lesions are thought never to do so. Consequently only midline lesions are usually imaged prior to surgery. We describe a lateral dermoid sinus communicating with an intracerebral dermoid cyst within the middle cranial fossa in a 3 year-old with recurrent periorbital cellulitis and intermittent discharge from a small pimple in the temporal region. This case demonstrates that some lateral "dermoids" need to be treated with more caution if there are unusual features such as dimpling, discharge of material or recurrent wider infection, and preoperative imaging should be carried out to exclude intracranial extension.