ALS-associated TBK1 variant p.G175S is defective in phosphorylation of p62 and impacts TBK1-mediated signalling and TDP-43 autophagic degradation.

Mutations affecting SQSTM1 coding for p62 and TANK-Binding Kinase 1 (TBK1) have been implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TBK1 is a serine-threonine kinase that regulates p62's activity as an autophagy receptor via phosphorylation and also has roles in neuroinflammatory signalling pathways. The mechanisms underlying ALS and FTLD pathogenesis as a result of TBK1 mutations are incompletely understood, however, loss of TBK1 function can lead to dysregulated autophagy and mitophagy. Here, we report that an ALS-associated TBK1 variant affecting the kinase domain, p.G175S, is defective in phosphorylation of p62 at Ser-403, a modification critical for regulating its ubiquitin-binding function, as well as downstream phosphorylation at Ser-349. Consistent with these findings, expression of p.G175S TBK1 was associated with decreased induction of autophagy compared to wild type and reduced degradation of the ALS-linked protein TDP-43. Expression of wild type TBK1 increased NF-κB signalling ~300 fold in comparison to empty vector cells, whereas p.G175S TBK1 was unable to promote NF-κB signalling above levels observed in empty vector transfected cells. We also noted a hitherto unknown role for TBK1 as a suppressor of oxidative stress (Nrf2) signalling and show that p.G175S TBK1 expressing cells lose this inhibitory function. Our data suggest that TBK1 ALS mutations may broadly impair p62-mediated cell signalling, which ultimately may reduce neuronal survival, in addition TDP-43 was not efficiently degraded, together these effects may contribute to TBK1 mutation associated ALS and FTLD pathogenesis.

An FTLD-associated SQSTM1 variant impacts Nrf2 and NF-κB signalling and is associated with reduced phosphorylation of p62.

Elevated oxidative stress has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). In response to oxidative stress, the Nrf2 transcription factor activates protective antioxidant genes. A critical regulator of Nrf2 is the inhibitory protein Keap1, which mediates Nrf2 degradation. In response to cellular stress an interaction between Keap1 and SQSTM1/p62 (p62), a signalling adaptor protein, allows for increased Nrf2 signalling as it escapes degradation. Mutations in SQSTM1 (encoding p62) are linked with ALS-FTLD. Previously, two ALS-FTLD-associated p62 mutant proteins within the Keap1 interacting region (KIR) of p62 were found to be associated with decreased Keap1-p62 binding and Nrf2 activation. Here we report that a non-KIR domain FTLD-associated variant of p62 (p.R110C), affecting a residue close to the N-terminal PB1 oligomerisation domain, also reduces Keap1-p62 binding in cellulo and thereby reduces Nrf2 activity in reporter assays. Further, we observed that expression of p.R110C increased NF-κB activation compared with wild type p62. Altered signalling appeared to be linked with reduced phosphorylation of p62 at Serine residues -349 and -403. Our results confirm that ALS-FTLD mutations affecting multiple domains of p62 result in a reduced stress response, suggesting that altered stress signalling may directly contribute to the pathology of some ALS-FTLD cases.

Do airline pilots and cabin crew have raised risks of melanoma and other skin cancers? Systematic review and meta-analysis.

BACKGROUND: Airline pilots and cabin crew are potentially exposed to hazardous ultraviolet and cosmic radiation, which may increase their risk of melanoma and other skin cancers. OBJECTIVES: To establish precise risks of melanoma and keratinocyte cancer (KC) for airline pilots and for cabin crew based on all studies published to date. METHODS: We searched MEDLINE, ISI Science Citation Index, Embase, SCOPUS and CINAHL to June 2018. All studies of melanoma and KC risk and mortality in airline pilots and cabin crew compared with the general population were eligible. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were pooled using random effects models. RESULTS: From 5866 papers retrieved, we reviewed 44 full-text articles, of which 12 studies with data collected mostly between the 1970s and 1990s were eligible for inclusion. The pooled SIR (pSIR) for melanoma in pilots was 2.03 [95% confidence interval (CI) 1.71-2.40] and in cabin crew it was 2.12 (95% CI 1.71-2.62). For pilots, the pooled SMR for melanoma was 1.99 (95% CI 1.17-3.40) and for cabin crew it was 1.18 (95% CI 0.73-1.89). For KC, the pSIR was 1.86 (95% CI 1.54-2.25) in pilots and 1.97 (95% CI 1.25-2.96) in cabin crew. There was no evidence of study heterogeneity. CONCLUSIONS: The available evidence shows that airline pilots and cabin crew have about twice the risk of melanoma and other skin cancers than the general population, with pilots more likely to die from melanoma. However, most of the evidence was collected several decades ago and their relevance to contemporary levels of risk is uncertain.

A feasibility study for a triple-blind randomized controlled trial investigating the effects of oral isotretinoin on mood and quality of life in patients with acne vulgaris.

Isotretinoin is used in the treatment of severe acne vulgaris (AV), but has controversially been associated with depression and suicide. Large prospective studies have failed to translate this clinically. We undertook a feasibility study to investigate the parameters of a triple-blind, randomized controlled trial (RCT) assessing the effect of oral isotretinoin on quality of life (QoL) and mood in patients with AV. Patients meeting the inclusion criteria were randomized for 2 weeks to isotretinoin or doxycycline. Participants completed verified depression and QoL screening questionnaires at baseline and week 2. In total, 194 patients with AV were screened, with 48 meeting the inclusion criteria and 13 of these being willing to participate. The follow-up rate was 92% and questionnaire response rate was 96%. To our knowledge, this is the first study to demonstrate a successful design for a triple-blind RCT investigating the effects of isotretinoin on mood in patients with AV.

Welfare indicators during broiler slaughtering.

1. The aim of this study was to identify the most relevant welfare indicators for unloading, lairage, stunning, killing and post-mortem inspection in a poultry slaughter plant. Different indicators were unloading duration, lairage time, environmental variables in the lairage facilities, shackling time and electrical variables used in the water bath. 2. Lairage time did not correlate strongly with dead on arrival. Heat stress was limited by means of ventilation systems, correct cage placement and appropriate stocking density per crate. The acceptable shackling period was about 30 s. 3. The presence of a corneal reflex showed that an animal was alive, while spontaneous wing flapping, spontaneous eye blinking and response to a painful stimulus were regarded as indicators of stunning efficiency. 4. It was concluded that the presence of recent traumatic injuries during the post-mortem inspection could be a valid means to establish whether corrective measures concerning the handling, transport and loading procedures should be taken.

The occurrence of giant fibres in different muscles of two chicken genotypes.

1. The occurrence of Giant Fibres (GF) in three muscles (Pectoralis major (PM), Iliotibialis lateralis and Semimembranosus) with different types of energy metabolism was studied in slow- and fast-growing chicken strains. 2. A total of 20 one-day-old Leghorn chicks (slow-growing) and 20 broiler (Ross 508) chicks (fast-growing) were reared to 100 and 45 d, respectively. 3. A small percentage of GF was seen in pre rigor muscle samples even at 3 min post mortem in both genotypes and in all muscle types studied. 4. From 3 min to 24 h post mortem GF increased both in Leghorn and broiler chickens but to a different extent according to muscle type and genotype. 5. The highest GF 24 h post mortem value was found in the PM muscles belonging to the fast-growing broiler line. 6. It was concluded that every type of muscle can develop GF, but this phenomenon is more evident in the PM especially in animals selected for increased growth rate.

p62 overexpression induces TDP-43 cytoplasmic mislocalisation, aggregation and cleavage and neuronal death.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) that exist on a spectrum of neurodegenerative disease. A hallmark of pathology is cytoplasmic TDP-43 aggregates within neurons, observed in 97% of ALS cases and ~ 50% of FTLD cases. This mislocalisation from the nucleus into the cytoplasm and TDP-43 cleavage are associated with pathology, however, the drivers of these changes are unknown. p62 is invariably also present within these aggregates. We show that p62 overexpression causes TDP-43 mislocalisation into cytoplasmic aggregates, and aberrant TDP-43 cleavage that was dependent on both the PB1 and ubiquitin-associated (UBA) domains of p62. We further show that p62 overexpression induces neuron death. We found that stressors (proteasome inhibition and arsenic) increased p62 expression and that this shifted the nuclear:cytoplasmic TDP-43 ratio. Overall, our study suggests that environmental factors that increase p62 may thereby contribute to TDP-43 pathology in ALS and FTLD.

Natural history and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution.

BACKGROUND: The study evaluates clinical presentation and outcome of differentiated thyroid cancer (DTC) on a large series of patients homogeneously managed. PATIENTS AND METHODS: A cohort of 1503 DTC followed according to a standardized protocol entered the study. Main outcome measures were clinical presentation at the diagnosis, survival, morbidity and prognostic risk factors. RESULTS: Median age at diagnosis was 46 years. Papillary cancer and low pathological tumor-node-metastasis stages represented >80% of cases. Cancer specific survival at 5, 10 and 15 years was 98.6%, 94.7% and 87.4%; 10-year disease-free and progression-free survivals were 96.8% and 17.1%, respectively. Cancer-specific mortality rate was 2.5% [95% confidence interval (CI) 1.7% to 3.4%], recurrence rate was 0.6 % while morbidity rate was 12.6% (95% CI 11% to 14%). Response to radioiodine treatment is the strongest predictor of a good outcome in multivariate analysis (hazard ratio 211, P < 0.0001). Other independent predictor variables are sex, age, histology and distant metastases for survival and metastases for morbidity. CONCLUSIONS: A rigorous initial therapeutic approach leads to a better survival and a very low morbidity. Patients who do not respond to radioiodine treatment have a worse prognosis.

Targeted sequencing of DCSTAMP in familial Paget's disease of bone.

Paget's disease of bone (PDB) has a strong genetic component. Variants in SQSTM1 are found in up to 40% of patients with a family history of the disease, where a pattern of autosomal dominance with incomplete penetrance is apparent. By contrast, SQSTM1 variants are only found in up to 10% of patients with sporadic disease. It has been hypothesised that the remaining genetic susceptibility to PDB, particularly in familial cases, could be explained by rare genetic variants in loci previously identified by Genome Wide Association Studies. It is likely that polygenic factors are involved in many individuals. In this study we utilised whole exome sequencing to investigate predisposing genetic factors in an unsolved PDB kindred and identified a c.1189C > T p.L397F variant in DC-STAMP, also known as TM7SF4, that co-segregated with disease. DCSTAMP was identified as a gene of interest in PDB following Genome Wide Association Studies and has been previously shown to play critical roles in osteoclast fusion. The variant we identified has also been reported in association with PDB in a French-Canadian cohort however the significance of this variant was inconclusive. Targeted screening of DCSTAMP in our familial cohort of PDB patients revealed an additional 8 variants; however we did not find a significant association between any of these, including p.L397F, with PDB. Osteoclastogenesis assays from the affected proband and his unaffected brother demonstrated an increase in osteoclast number and nucleation, consistent with the pagetic phenotype. In converse to other established Paget's associated genetic variations such as SQSTM1, TNFRSF11A and OPTN, expression of the mutant DC-STAMP protein attenuated the activation of transcription factors NFκB and AP-1 when exogenously expressed. We found that the p.L397F variant did not influence the subcellular localization of the protein. Based on these findings we conclude that genetic variation in DCSTAMP is not a significant predisposing factor in our specific cohort of PDB patients and the p.L397F variant is unlikely to be a contributing factor in PDB pathogenesis.

Males absent on the first (MOF): from flies to humans.

Histone modifications such as acetylation, methylation and phosphorylation have been implicated in fundamental cellular processes such as epigenetic regulation of gene expression, organization of chromatin structure, chromosome segregation, DNA replication and DNA repair. Males absent on the first (MOF) is responsible for acetylating histone H4 at lysine 16 (H4K16) and is a key component of the MSL complex required for dosage compensation in Drosophila. The human ortholog of MOF (hMOF) has the same substrate specificity and recent purification of the human and Drosophila MOF complexes showed that these complexes were also highly conserved through evolution. Several studies have shown that loss of hMOF in mammalian cells leads to a number of different phenotypes; a G2/M cell cycle arrest, nuclear morphological defects, spontaneous chromosomal aberrations, reduced transcription of certain genes and an impaired DNA repair response upon ionizing irradiation. Moreover, hMOF is involved in ATM activation in response to DNA damage and acetylation of p53 by hMOF influences the cell's decision to undergo apoptosis instead of a cell cycle arrest. These data, highlighting hMOF as an important component of many cellular processes, as well as links between hMOF and cancer will be discussed.

Use of the Internet by burns patients, their families and friends.

INTRODUCTION: The Internet has also become an increasingly important source of health-related information. However, with this exponential increase comes the problem that although the volume of information is huge, the quality, accuracy and completeness of the information are questionable, not only in the field of medicine. Previous studies of single medical conditions have suggested that web-based health information has limitations. The aim of this study was to evaluate Internet usage among burned patients and the people accompanying them to the outpatient clinic. METHODS: A customised questionnaire was created and distributed to all patients and accompanying persons in the adult and paediatric burns clinics. This investigated computer usage, Internet access, usefulness of Internet search and topics searched. RESULTS: Two hundred and ten people completed the questionnaire, a response rate of 83%. Sixty three percent of responders were patients, parents 21.9%, spouses 3.3%, siblings, children and friends the remaining 10.8%. Seventy seven percent of attendees had been injured within the last year, 11% between 1 and 5 years previously, and 12% more than 5 years previously. Seventy four percent had computer and Internet access. Twelve percent had performed a search. Topics searched included skin grafts, scarring and scar management treatments such as pressure garments, silicone gel and massage. DISCUSSION: This study has shown that computer and Internet access is high, however a very small number actually used the Internet to access further medical information. Patients with longer standing injuries were more likely to access the Internet. Parents of burned children were more frequent Internet users. As more burn units develop their own web sites with information for patients and healthcare providers, it is important to inform patients, family members and friends that such a resource exists. By offering such a service patients are provided with accurate, reliable and easily accessible information which is appropriate to their needs.

MSL proteins and the regulation of gene expression.

Epigenetics describes changes in genome function that occur without a change in the DNA sequence. Dosage compensation is a prime example of the regulation of gene expression by an epigenetic mechanism. Dosage compensation has evolved to balance the expression of sex-linked genes in males and females, which possess different numbers of sex chromosomes. However, the genetic sequence of the chromosomes is the same in both sexes. This mechanism therefore needs (1) to function in a sex-specific manner, (2) to target the sex chromosome from amongst the autosomes and (3) to establish and maintain through development a precise, equalised level of gene expression in one sex compared to the other. The process by which dosage compensation is orchestrated has been well characterised in fruit flies and mammals. Although each has evolved a specific dosage-compensation mechanism, these systems share some underlying themes; the molecular components that mediate dosage compensation in both include non-coding RNA molecules, which act as nucleation points for the compensation process. Both systems utilise chromatin-modifying enzymes to remodel large domains of a chromosome. This review will discuss the mechanism of dosage compensation in Drosophila in light of recent developments that have brought into question the previous model of dosage compensation.

Isolation and characterization of Suv39h2, a second histone H3 methyltransferase gene that displays testis-specific expression.

Higher-order chromatin has been implicated in epigenetic gene control and in the functional organization of chromosomes. We have recently discovered mouse (Suv39h1) and human (SUV39H1) histone H3 lysine 9-selective methyltransferases (Suv39h HMTases) and shown that they modulate chromatin dynamics in somatic cells. We describe here the isolation, chromosomal assignment, and characterization of a second murine gene, Suv39h2. Like Suv39h1, Suv39h2 encodes an H3 HMTase that shares 59% identity with Suv39h1 but which differs by the presence of a highly basic N terminus. Using fluorescent in situ hybridization and haplotype analysis, the Suv39h2 locus was mapped to the subcentromeric region of mouse chromosome 2, whereas the Suv39h1 locus resides at the tip of the mouse X chromosome. Notably, although both Suv39h loci display overlapping expression profiles during mouse embryogenesis, Suv39h2 transcripts remain specifically expressed in adult testes. Immunolocalization of Suv39h2 protein during spermatogenesis indicates enriched distribution at the heterochromatin from the leptotene to the round spermatid stage. Moreover, Suv39h2 specifically accumulates with chromatin of the sex chromosomes (XY body) which undergo transcriptional silencing during the first meiotic prophase. These data are consistent with redundant enzymatic roles for Suv39h1 and Suv39h2 during mouse development and suggest an additional function of the Suv39h2 HMTase in organizing meiotic heterochromatin that may even impart an epigenetic imprint to the male germ line.

Sentinel node biopsy in cutaneous melanoma: correlations between melanoma prognostic factors and sentinel node status.

This study aims to correlate the most important prognostic factors of primary melanoma with sentinel node (SN) positive for metastases. We have enrolled 84 patients subjected to sentinel node biopsies for cutaneous melanomas of Breslow's thickness > or = 0.75 mm by using an intra-operative gamma probe after lymphoscintigraphy, without blue dye support. SN metastases were reported in 27% of cases (14% by histology and 13% by immunohistochemistry). By chi-square test Breslow's thickness > 2mm (p= 0.004), IV and V Clark's level (p= 0.02), ulceration (p= 0.05) and high mitotic rate (p= 0.05) were statistically significant (p < 0.05) with reference to SN positive for metastases, unlike the site of cutaneous melanoma, vertical growth phase, tumour infiltrating lymphocytes, regression and vascular invasion. Breslow's thickness remains the first prognostic factor to be considered for sentinel node biopsy in cutaneous melanoma, but other markers must be carefully estimated.

A novel synaptobrevin/VAMP homologous protein (VAMP5) is increased during in vitro myogenesis and present in the plasma membrane.

cDNA clones encoding a novel protein (VAMP5) homologous to synaptobrevins/VAMPs are detected during database searches. The predicted 102-amino acid VAMP5 harbors a 23-residue hydrophobic region near the carboxyl terminus and exhibits an overall amino acid identity of 33% with synaptobrevin/VAMP1 and 2 and cellubrevin. Northern blot analysis reveals that the mRNA for VAMP5 is preferentially expressed in the skeletal muscle and heart, whereas significantly lower levels are detected in several other tissues but not in the brain. During in vitro differentiation (myogenesis) of C2C12 myoblasts into myotubes, the mRNA level for VAMP5 is increased approximately 8- to 10-fold. Immunoblot analysis using antibodies specific for VAMP5 shows that the protein levels are also elevated approximately 6-fold during in vitro myogenesis of C2C12 cells. Indirect immunofluorescence microscopy and immunoelectron microscopy reveal that VAMP5 is associated with the plasma membrane as well as intracellular perinuclear and peripheral vesicular structures of myotubes. Epitope-tagged versions of VAMP5 are similarly targeted to the plasma membrane.

Burns first aid information on the Internet.

The Internet is an increasingly important source of health-related information. However, the growth of the Internet and its use as a medical delivery tool should be viewed with caution. One of the key concerns is that although the volume of information is huge, the quality, accuracy and completeness of the information is questionable. The aim of this study was to evaluate burns first aid information on the Internet. The search term used was "first aid for burns" and the first 25 hits from each search engine were analysed by one of the observers. We gathered basic information on the web sites--such as the country of origin, language in which the information was offered, accessibility, relevance and whether the site was commercial, organisational or academic. Quality and technicality of the web sites were assessed and scored. The mean quality score was 4.7/15 (31.5%) The mean technical score was 6.1 of 12 (51.1%). When the total score was categorised by percentage, none of the web sites ranked in the excellent category, 1 was very good, 4 were good, 6 were fair and the majority, 36, were poor. Based on the quality score only, two web sites were in the excellent category and two were very good. For technicality one web site was excellent and three were very good. This study has shown first aid information on the Internet is largely of poor quality, that the technical information provided is inadequate and that the sites include a significant amount of grossly inaccurate information. The few sites that contain excellent technical information make up a very small proportion of what is available. Therefore, the average Internet user may not encounter these resources, instead gaining knowledge from sites of questionable value.

Electroconvulsive Therapy - What Do Patients Think Of Their Treatment?

BACKGROUND: The Regulation and Quality Improvement Authority (RQIA) monitors the administration of electroconvulsive therapy (ECT) in Northern Ireland (NI). As part of their inspection methodology RQIA wished to include feedback from ECT patients. The aim of this report is to summarise the opinions of ECT patients over a 1-year period and to compare their feedback about treatment with the standards of best practice, as defined by the Electroconvulsive Therapy Accreditation Service (ECTAS). METHOD: RQIA was granted permission to use the ECTAS patient questionnaire. The questionnaire was distributed to all the ECT clinics in NI and staff were requested to give them to patients who had received a course of ECT. RESULTS: A total of 42 individuals returned questionnaires, 24 females (57.1%) and 18 (42.9%) males. The response rate was 26%. Almost half of respondents were detained under the Mental Health (Northern Ireland) Order 1986 (n=19, 45.2%), with one third receiving ECT as a day patient (n=14, 33.3%). Respondents reported having detailed information about ECT, with ECTAS standards 4.2 and 4.3 being affirmed in over 80% of cases. Eighty percent of respondents (n=34) believed they benefited from ECT. CONCLUSION: The results are mainly favourable towards ECT. The majority felt they benefited from treatment.

Moving GLUT4: the biogenesis and trafficking of GLUT4 storage vesicles.

The GLUT4 system in muscle and fat cells plays an important role in whole-body glucose homeostasis. Insulin stimulates the translocation of GLUT4 from an intracellular storage compartment to the cell surface. The nature of this compartment remains largely unknown. We review recent studies describing the biogenesis and molecular constituents of the GLUT4 storage compartment and conclude that it is segregated from the endosomal and biosynthetic pathways. Further, we present evidence to suggest that the GLUT4 storage compartment moves directly to the plasma membrane in response to insulin and, hence, is analogous to small synaptic vesicles in neurons. We propose that the GLUT4 storage compartment be referred to as GLUT4 storage vesicles or GSVs.

Phase 1B study of subcutaneously administered interleukin 2 in combination with 13-cis retinoic acid as maintenance therapy in advanced cancer.

At present, no therapeutic strategy is available to maintain responses achieved in patients treated with chemotherapy. This Phase IB study was aimed at identifying the optimal biological dose of chronic maintenance therapy using s.c. interleukin (IL) 2 and oral 13-cis retinoic acid (RA) in patients with either tumor stabilization or response to chemotherapy. IL-2 has no cross-resistance with chemotherapy and improves cancer-related lymphocytopenia, a factor that determines poor prognosis, whereas RA has immunomodulatory properties, potentially synergistic with IL-2. Eighteen patients with advanced solid tumor who achieved a response or stable disease as a result of standard chemotherapy, received RA (0.5 mg/kg) and IL-2 5 days/week for two cycles of 3 weeks/month for up to 1 year. Three doses of IL-2 were used: 9.0, 4.5, and 1.8 x 10(6) IU/day. Monitoring consisted in a weekly blood differential count and a bimonthly assessment of tumor markers, CD4+, CD8+, and natural killer cells. Patients were evaluated for toxicity, response maintenance, time to progression, and survival. Patients chronically treated with 9 and 4.5 x 10(6) IU of IL-2 developed dose-limiting toxicity grade III or IV, consisting of fever, fatigue, thrombocytopenia, mucositis, and local cutaneous reaction. No grade III or IV toxicity was observed with the 1.8 x 10(6) IU dose, considered as the optimal biological dose. Fifty courses of IL-2 were administered (median, 3 per patient). An increase in total lymphocyte number, CD4:CD8 ratio and natural killer cell count was observed at all of the three dose levels with respect to baseline values. Two patients with a partial response to chemotherapy achieved a complete response after 6 and 7 months, respectively, of IL-2 + RA maintenance therapy. Median time to progression and overall survival were, respectively, 8.1 and 13.7 months (range, 2-48.8+ months). Low-dose IL-2 + RA as maintenance therapy after chemotherapy is, therefore, feasible and well tolerated and improves immunological parameters known to have a prognostic value in cancer.

Minor burn injuries in adults presenting to the regional burns unit in Western Australia: a prospective descriptive study.

INTRODUCTION: Western Australia is the largest state in Australia, accounting for approximately one third of the Australian continent. The adult Burns Unit in Western Australia is at Royal Perth Hospital, which provides for the whole adult population of approximately 1.8 million, 80% of which live in and around the state capital city, Perth (approx. 1.4 million). The unit also offers a minor burn care facility. METHODS: The aim of this study was to perform the first prospective review of minor burn injuries in Western Australia, to classify patient demographics, injury patterns and primary treatment. RESULTS AND CONCLUSION: Two hundred and twenty seven patients were referred to the minor burn facility at Royal Perth Hospital (RPH) during the study period. One hundred and three patients (45%) sustained a scald, a further 44 (19%) received a flame burn. Thirty-seven (16%) patients sustained a contact burn, 18 (7.8%) patients attended the clinic with a chemical burn. Sixty percent of all patients reviewed had burns less than one percent. Only 39% of all our patients received adequate first aid. Sixty one percent of all patients received inadequate or inappropriate first aid. This study highlights a number of important issues. The over representation of metropolitan patients coupled with the low numbers of aboriginal patients reinforces the need for rural burns education. The best service we can provide is education on burns prevention and primary management. There are a number of other areas we hope to address in the future, the high incidence of domestic accidents, home safety must be a priority, coupled with seasonal promotional campaigns to address issues such as car radiator injuries. The most striking, and perhaps the most worrying finding in this study is the poor application of basic first aid principles. This is something that is unacceptable, needs further investigation and the lack of basic knowledge needs to be addressed at all levels of the community.