Correction: The biotoxin BMAA promotes dysfunction via distinct mechanisms in neuroblastoma and glioblastoma cells.

[This corrects the article DOI: 10.1371/journal.pone.0278793.].

Incidence of feline idiopathic cystitis and urethral obstruction during COVID-19 human movement restrictions in Queensland, Australia.

OBJECTIVES: Feline idiopathic cystitis (FIC) and urethral obstruction (UO) are commonly linked to increased stress. The influence of human movement restrictions on their incidence remains undetermined. FIC with or without UO is associated with environmental stress factors. The severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic restricted human movement and working behaviours. It is unknown if these restrictions increased the risk of FIC or UO in cats. METHODS: Total cat emergency accessions and transfers between 8 February 2019 and 8 February 2021 at two private hospitals were retrospectively reviewed. Cats were included in the FIC group if they presented with lower urinary tract signs and supporting urinalysis, and were included in the UO group if they presented with UO. Cats with current urinary tract infection, or previous FIC or UO, were excluded. Groups were considered 'pre-COVID-19' between February 2019 and 2020 and 'COVID-19' between February 2020 and 2021. Cases of FIC and UO were compared between COVID-19 and pre-COVID-19 using Fisher's exact test and relative risk (RR) calculations. RESULTS: The pre-COVID-19 incidence of FIC was 4.3% (63/1477, 95% confidence interval [CI] 0.0332-0.053), non-obstructive FIC was 1.4% (20/1477, 95% CI 0.008-0.020) and UO was 2.9% (43/1477, 95% CI 0.020-0.038). One cat was excluded as obstruction occurred during hospitalisation. The COVID-19 incidence of FIC was 5.4% (113/2081, 95% CI 0.044-0.64), non-obstructive FIC was 2.1% (70/2081, 95% CI 0.014-0.027) and UO was 3.4% (70/2081, 95% CI 0.026-0.042). The risk of non-obstructive FIC (P = 0.122; RR 0.652, 95% CI 0.387-1.096), UO (P = 0.382; RR 0.839, 95% CI 0.577-1.22) or either (P = 0.098; RR 0.773, 95% CI 0.572-1.044) was not significantly higher in the COVID-19 period than the pre-COVID-19 period. CONCLUSIONS AND RELEVANCE: No clear association between COVID-19 movement restrictions and the incidence of UO or non-obstructive FIC was found within this retrospective population.

Improved Survival Outcomes with Surgical Resection Compared to Ablative Therapy in Early-Stage HCC: A Large, Real-World, Propensity-Matched, Multi-Centre, Australian Cohort Study.

The optimal treatment approach in very-early and early-stage hepatocellular carcinoma (HCC) is not precisely defined, and there is ambiguity in the literature around the comparative efficacy of surgical resection versus ablation as curative therapies for limited disease. We performed this real-world propensity-matched, multi-centre cohort study to assess for differences in survival outcomes between those undergoing resection and those receiving ablation. Patients with Barcelona Clinic Liver Cancer (BCLC) 0/A HCC first diagnosed between 1 January 2016 and 31 December 2020 who received ablation or resection as initial treatment were included in the study. A total of 450 patients were included in the study from 10 major liver centres including two transplant centres. Following propensity score matching using key covariates, 156 patients were available for analysis with 78 in each group. Patients who underwent resection had significantly improved overall survival (log-rank test p = 0.023) and local recurrence-free survival (log rank test p = 0.027) compared to those who received ablation. Based on real-world data, our study supports the use of surgical resection in preference to ablation as first-line curative therapy in appropriately selected BCLC 0/A HCC patients.

Eosinophilic oesophagitis: a common cause of food bolus obstruction.

BACKGROUND: Eosinophilic oesophagitis (EOE) is a known cause of food bolus obstruction (FBO) with rising incidence and prevalence. AIMS: To assess the rates of EOE in adult cases presenting with an FBO via prospective biopsy collection during index endoscopy. METHODS: Oesophageal FBO cases requiring gastroscopy between February 2014 and January 2021 at a single institution with a unified policy to perform biopsies on FBO cases were analysed using medical records, endoscopy and histology. Statistical analysis was undertaken to compare those with and without EOE as their final diagnosis, including the timing of oesophageal biopsy and the season that cases presented. RESULTS: One hundred ninety FBO presentations were analysed, 15 patients presented twice and one patient presented four times within the 7-year study period. Men represented 72% of cases. A total of 78% of cases had biopsies collected at an index or scheduled follow-up endoscopy. EOE was the cause of the FBO in 28% (53/190) of presentations. FBO secondary to EOE was more likely to occur in the spring and summer months (Australian September to March), with 39% (19 of 49) of cases presenting in spring attributable to EOE. CONCLUSION: EOE affects a significant proportion of patients presenting with FBO (28%); a high biopsy rate of 78% in FBO cases provides an opportunity for prompt diagnosis and treatment.

The biotoxin BMAA promotes dysfunction via distinct mechanisms in neuroblastoma and glioblastoma cells.

Chronic exposure to the Cyanobacteria biotoxin Beta-methylamino-L-alanine (BMAA) has been associated with development of a sporadic form of ALS called Amyotrophic Lateral Sclerosis/Parkinsonism-Dementia Complex (ALS/PDC), as observed within certain Indigenous populations of Guam and Japan. Studies in primate models and cell culture have supported the association of BMAA with ALS/PDC, yet the pathological mechanisms at play remain incompletely characterized, effectively stalling the development of rationally-designed therapeutics or application of preventative measures for this disease. In this study we demonstrate for the first time that sub-excitotoxic doses of BMAA modulate the canonical Wnt signaling pathway to drive cellular defects in human neuroblastoma cells, suggesting a potential mechanism by which BMAA may promote neurological disease. Further, we demonstrate here that the effects of BMAA can be reversed in cell culture by use of pharmacological modulators of the Wnt pathway, revealing the potential value of targeting this pathway therapeutically. Interestingly, our results suggest the existence of a distinct Wnt-independent mechanism activated by BMAA in glioblastoma cells, highlighting the likelihood that neurological disease may result from the cumulative effects of distinct cell-type specific mechanisms of BMAA toxicity.

Alcohol intake is associated with a decreased risk of developing primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic progressive liver disease of unknown aetiology characterised by immune-mediated destruction of small and medium-sized intrahepatic bile ducts. There are few well-established risk factors and epidemiological studies are needed to further evaluate the pathogenesis of the disease. AIM: To evaluate the relationship between alcohol intake, smoking and marijuana use with PBC development. METHODS: We conducted a prevalent case control study of 200 cases and 200 age (within a five year age band) and sex-matched controls, identified from the Victorian PBC prevalence study. We assessed lifetime alcohol intake and smoking behaviour (both tobacco and marijuana) prior to PBC onset and used conditional logistic regression for analyses. RESULTS: Alcohol intake consistently showed a dose-dependent inverse association with case status, and this was most substantial for 21-30 years and 31-40 years (P trend < 0.001). Smoking was associated with PBC, with a stronger association with a longer duration of smoking [e.g., adjusted OR 2.27 (95%CI: 1.12- 4.62) for those who had smoked for 20-35 years]. There was no association between marijuana use and PBC. CONCLUSION: Alcohol appears to have an inverse relationship with PBC. Smoking has been confirmed as an environmental risk factor for PBC. There was no association between marijuana use and PBC.

Predictive value of symptoms, signs and biomarkers on computed tomography pulmonary angiogram results.

BACKGROUND: Pulmonary embolism (PE) is associated with significant morbidity and mortality. PE is a heterogeneous entity that causes a wide variety of clinical presentations, making it imperative to establish which clinical symptoms, signs and biomarkers can influence the pretest probability of PE to aid clinicians and reduce over testing. AIM: To analyse the clinical parameters used by clinicians to order a computed tomography pulmonary angiogram (CTPA) and establish which were associated with the presence of PE. METHODS: Medical records of patients who underwent CTPA from December 2015 to March 2016 were extracted. Patient demographics, clinical symptoms, diagnostic and radiological results were analysed. RESULTS: The study included 150 CTPA studies. Of the studies, 25 were positive for PE and 125 were negative. There was no significant relationship between the presence or character of chest pain and a positive CTPA result (P = 0.216). Previous history of venous thromboembolism (VTE) (P < 0.0001), one or more risk factors for VTE and positive troponin (P < 0.002) were all predictive of PE. None of the patients with a negative D-dimer had a positive CTPA. CONCLUSION: This study supports the negative predictive value of the D-dimer for excluding PE and demonstrates that the strongest pretest predictors of PE in our population are a prior history of VTE, risk factors for VTE and elevated troponin. None of the parameters that often generate requests for CTPA, including vital signs or the presence of chest pain, was associated with the presence of PE in our study population.

Trends in Food and Beverage Portion Sizes in Australian Children; a Time-Series Analysis Comparing 2007 and 2011-2012 National Data.

In 2011-2012 approximately 26% of Australian children aged between 5-17 years were reported to be overweight or obese. Furthermore, the increase in prevalence of overweight and obesity among US children parallels reported increases in energy intake and portion sizes of common foods, leading to the recognition that availability of larger portion sizes contributes to the rise in overweight and obesity prevalence. Thus, the aim of this time-series analysis was to investigate whether selected food portion sizes in Australian children aged 2-16 years changed between 2007 and 2011-2012. Portion size data from 24-h recalls collected in Australian nutrition surveys were compared between 2007 and 2011-2012. Portion sizes changed significantly in 23% of items with increases in 15% and decreases in 8%. Changes in portion sizes varied by age, sex, and food group. Changes occurred for many meat-based items, energy-dense, nutrient-poor food items, breads, cereals, and some fruits and vegetables. Vegetable and fruit portion sizes were below the respective serving sizes of 75 g and 150 g in the Australian Guide to Healthy Eating, while portion sizes of some energy-dense, nutrient-poor foods have increased. These findings suggest approaches to increasing consumption of nutrient-dense core foods and reducing energy-dense, nutrient-poor food items in children are warranted.

Could low Safety Attitudes Questionnaire scores be indicative of an environment where it may be difficult to get new training practices established?

Introduction: Simulation-based, multiprofessional team training (SBMPTT) is used widely in healthcare, with evidence that it can improve clinical outcomes and be associated with a positive safety culture. Our aim was to explore the impact of introducing this type of training to a gynaecological team. Methods: In this interrupted time-series study, 'Safety Attitudes Questionnaire' (SAQ) data was collected both before and after SBMPTT was introduced to a gynaecological team. Results: Low baseline SAQ scores coincided with difficulty in establishing the training, meaning that at the end of our study period only a small proportion of staff had actually attended a training session. Despite trends towards improvement in scores for safety climate, teamwork climate and job satisfaction, no statistically significant difference was observed. There was however an improved perception of the level of collaboration between nursing staff and doctors after the introduction of training. Conclusions and Discussion: In this paper we explore a hypothesis that low baseline SAQ scores may highlight that the multiprofessional teams most in need of training work in environments where it is more challenging to implement. There is evidence from other specialties that multiprofessional team training works, now we need to understand how to address the barriers to getting it started. In this paper we suggest how the SAQ could be used as a directive tool for improvement; using the detailed analysis of the local safety culture it provides to both inform future training design and also provide management with an objective marker of progress.

Validity of the Australian Recommended Food Score as a diet quality index for Pre-schoolers.

BACKGROUND: Diet quality tools provide researchers with brief methods to assess the nutrient adequacy of usual dietary intake. This study describes the development and validation of a pediatric diet quality index, the Australian Recommended Food Scores for Pre-schoolers (ARFS-P), for use with children aged two to five years. METHODS: The ARFS-P was derived from a 120-item food frequency questionnaire, with eight sub-scales, and was scored from zero to 73. Linear regressions were used to estimate the relationship between diet quality score and nutrient intakes, in 142 children (mean age 4 years) in rural localities in New South Wales, Australia. RESULTS: Total ARFS-P and component scores were highly related to dietary intake of the majority of macronutrients and micronutrients including protein, ß-carotene, vitamin C, vitamin A. Total ARFS-P was also positively related to total consumption of nutrient dense foods, such as fruits and vegetables, and negatively related to total consumption of discretionary choices, such as sugar sweetened drinks and packaged snacks. CONCLUSION: ARFS-P is a valid measure that can be used to characterise nutrient intakes for children aged two to five years. Further research could assess the utility of the ARFS-P for monitoring of usual dietary intake over time or as part of clinical management.

Food and beverage portion sizes in Australian children: a secondary analysis of 1995 and 2007 national data.

BACKGROUND: Portion size of foods is reported to contribute to the rise in obesity prevalence. However, evidence of changes in portion size for commonly consumed foods in Australia is lacking. The aim was to evaluate whether Australian child and adolescent portion sizes of selected foods changed from 1995 to 2007. METHODS: Time-series study, comparing dietary data from two national cross-sectional surveys in nationally representative population survey of Australian households. The dietary data was from children aged 2-16 years who participated in the 1995 National Nutrition Survey (n = 2198) and 2007 Australian National Children's Nutrition and Physical Activity Survey (n = 4799). RESULTS: Differences were found across survey years in median portion size of common foods and beverages assessed by 24-hour recalls for age and sex categories. Of the 61 foods items evaluated across the whole population sample, portion size increased in 18 items, decreased in 22, with no change in 20, although the magnitude of change varied by age and sex. Decreases in portion size were detected for most dairy products, breakfast cereal, some packaged snack foods and vegetables, p < 0.0001. Increases were detected for cooked chicken, mixed chicken dishes, bacon and ham (p < 0.0001), cooked meat (p < 0.05), fish (p < 0.01) and pizza (p < 0.0001). No significant changes were detected for many items including white and wholemeal bread, mincemeat, chocolate and soft drink. CONCLUSIONS: Small changes in portion sizes were detected over 12 years in Australian children and adolescents with the degree of change varying by sex, age and food group. Knowledge of usual portion sizes could inform programs targeting appropriate serving sizes selection in children and adolescents.

Is there a place for e-learning in clinical skills? A survey of undergraduate medical students' experiences and attitudes.

BACKGROUND: e-learning is established in many medical schools. However the effectiveness of e-learning has been difficult to quantify and there have been concerns that such educational activities may be driven more by novelty, than pedagogical evidence. Where some domains may lend themselves well to e-learning, clinical skills has been considered a challenging area for online learning. AIMS: The aims of this study are to assess undergraduate medical students? perceived level of IT ability and accessibility, and attitudes towards e-learning in basic clinical skills education, compared to other teaching methods. METHODS: A self-administered questionnaire was developed to capture undergraduate medical students: (i) demographic details (ii) perceived level of IT ability and accessibility (iii) experiences and attitudes towards e-learning and clinical skills training. Responses were linked to student?s performance in a clinical skills OSCE. RESULTS: The majority of students reported good access to computers and the internet, both on and off campus and appear confident using IT. Overall students felt that e-learning had a positive impact on their learning of clinical skills and was comparable to other traditional forms of clinical skills teaching. Students who displayed deep learning traits when using e-learning, performed better in clinical skills OSCEs. CONCLUSION: Undergraduate medical students value the use of e-learning in clinical skills education, however they vary in their utilization of such learning environments. Students rate e-learning just as highly as other traditional methods of clinical skills teaching and acknowledge its integration in a blended approach. Developers of clinical skills curricula need to ensure e-learning environments utilize media that encourage deeper approaches to learning.

Neurostimulatory therapeutics in management of treatment-resistant depression with focus on deep brain stimulation.

Treatment-resistant depression continues to pose a major medical challenge, as up to one-third of patients with major depressive disorder fail to have an adequate response to standard pharmacotherapies. An improved understanding of the complex circuitry underlying depressive disorders has fostered an explosion in the development of new, nonpharmacological approaches. Each of these treatments seeks to restore normal brain activity via electrical or magnetic stimulation. In this article, the authors discuss the ongoing evolution of neurostimulatory treatments for treatment-resistant depression, reviewing the methods, efficacy, and current research on electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, focal electrically administered stimulated seizure therapy, transcranial direct current stimulation, chronic epidural cortical stimulation, and vagus nerve stimulation. Special attention is given to deep brain stimulation, the most focally targeted approach. The history, purported mechanisms of action, and current research are outlined in detail. Although deep brain stimulation is the most invasive of the neurostimulatory treatments developed to date, it may hold significant promise in alleviating symptoms and improving the quality of life for patients with the most severe and disabling mood disorders.