Changes in the balance between proliferation and apoptosis during the progression of malignancy in thyroid tumours

The aim of this study was to gain better insight into molecular changes which reflect disturbances in the balance between proliferation and apoptosis during progression of thyroid malignancy from papillary microcarcinoma (PMC) via clinically manifest papillary carcinoma (PTC) to anaplastic carcinoma (ATC). The apoptosis related molecules (Bcl-2, Bax) and proliferation related marker (PCNA) were analysed immunohistochemically in 120 archival cases comprising PMC (n=34), PTC (n=52) and ATC (n=34). In addition, in situ apoptotic cell death was analysed by the TUNEL method. The average Bcl-2 staining score did not differ between PMC and PTC (p>0.05), but was significantly lower in ATC (p<0.05).The Bax score was higher in PTCs and ATCs than in PMCs (p<0.05). Due to these changes, the Bcl-2/Bax ratio showed a marked decrease from PMC to ATC (p<0.05), while proliferation activity increased significantly from PTC to ATC (p<0.05). Despite high Bax expression, the rate of apoptotic cell death was low in the investigated carcinomas, especially in ATC, i.e. the increase in proliferative activity was not counterbalanced with appropriate cell death. Differences were found in the expression of apoptotic molecules (Bcl-2 and Bax), their ratio (Bcl-2 /Bax) and in the rate of apoptotic cell death and proliferative activity between PMC, PTC and ATC, indicating that disturbances in the balance between apoptosis and proliferation, in favour of the latter, occur gradually during the progression of malignancy in thyroid tumours

Factors associated with acute care service use after epilepsy hospitalisation in people with intellectual disability

Background: This study aimed to identify factors associated with unplanned acute hospital readmission and emergency department (ED) presentation after hospitalisation for epilepsy in people with intellectual disability (ID). Methods: This study is a retrospective cohort study using linked administrative datasets. We identified 3293 people with ID aged 5–64 years with a hospitalisation for epilepsy between 2005 and 2014 in New South Wales, Australia. We examined unplanned readmission and ED presentation within 30 or 365 days and associations with demographic, socio-economic and health status variables. Modified Poisson regression with robust estimation was used to model outcomes within 30 days. Negative binomial regression was used to account for the overdispersion of the data and to model 365-day outcome rates. Results: Around half of the cohort had an unplanned readmission and ED presentation within 365 days of the index hospitalisation. In fully adjusted models, being female, being a young adult and having a longer or acute care index admission, mental and physical comorbidities and a history of incarceration were associated with an elevated risk of readmission or ED presentation. The strongest association was observed between history of self-harm and 365-day readmission (incidence rate ratio 2.15, 95% confidence interval 1.41–3.29). Conclusions: Socio-demographic, justice and health factors are associated with unplanned readmission and ED presentation risk after hospitalisation for epilepsy in people with ID. Interventions targeting improving continuity of care should be tailored for individuals and their support workers. The findings also emphasise the importance of person-centred multidisciplinary care across different health sectors

Risk factors for dementia and self-harm: A linkage study

Introduction: People living with dementia experience poor mental health and high rates of self-harm. We investigated risk factors for self-harm in people aged > 40 years living with dementia and risk factors for dementia after self-harm. Methods: Using linked hospital data from New South Wales, Australia, we defined a dementia cohort (n = 154,811) and a self-harm cohort (n = 28,972). Using survival analyses, we investigated predictors of self-harm for the dementia cohort, and predictors of dementia for the self-harm cohort. Results: We found self-harm or dementia diagnoses occurred most often within 24 months of a dementia diagnosis or initial self-harm presentation, respectively. Men living with dementia, and people with complex psychiatric profiles, had the greatest risk of self-harm. Men who had self-harmed had the greatest risk of dementia diagnoses. Discussion: Men and people with complex psychiatric profiles and dementia may particularly benefit from post-diagnosis mental and behavioral support to reduce risk of self-harm

The efficacy of the thyroid peroxidase marker for distinguishing follicular thyroid carcinoma from follicular adenoma

Aim: Expression of thyroid peroxidase (TPO) in the thyroid gland tissue is well known as a sensitive marker of the thyroid malignancy. We have evaluated immunohistochemical assay of TPO for distinguishing follicular thyroid carcinoma from follicular adenoma. Materials and Methods: Sections of formalin-fixed tissues obtained from 92 patients with thyroid tumors (52 follicular carcinomas and 40 follicular adenomas including the Hurthle cell type) were analyzed using a monoclonal antibody (TPO mAb 47) and the avidin-biotin peroxidase complex immunohistochemical technique. Lesions with staining of more than 80% of the follicular cells/specimen were considered benign, while less than 80% were considered malignant. Results: TPO immunostaining correlated with the histopathological diagnosis in 24/40 cases of follicular adenomas and 41/52 cases of follicular carcinomas, giving a specificity of 60% and a sensitivity of 79%. Conclusion: These results suggest that immunohistochemical assay of TPO expression has limited value for the differential diagnosis of follicular thyroid carcinoma from thyroid follicular adenoma.Цель: уровень экспрессии тироидной пероксидазы (ТПО) в ткани щитовидной железы является чувствительным маркером малигнизации этого органа. В работе представлено попытку оценки метода иммуногистохимический детекции ТПО для дифференциальной диагностики фолликулярной карциномы и фолликулярной аденомы щитовидной железы (ФКЩЖ и ФАЩЖ соответственно). Материалы и методы: срезы ткани, зафиксированные в формалине, были получены у 92 пациентов с опухолями щитовидной железы (52 случая — ФКЩЖ и 40 — ФАЩЖ, в том числе тип с клетками Хюртля). Для иммуногистохимического анализа этих срезов использовали моноклональные антитела против ТПО (ТРОmAb47) и авидин-биотиновый комплекс. Препараты опухолей, содержащих более 80% позитивно окрашенных фолликулярных клеток, признавали доброкачественными, а те, что содержали менее 80% таких клеток, — злокачественными. Результаты: интенсивность иммуноокрашивания препаратов коррелировала с гистопатологическим диагнозом в 24 из 40 случаев ФАЩЖ и в 41 из 52 случаев ФКЩЖ. При этом чувствительность метода составляла 79%, специфичность — 60%. Выводы: иммуногистохимический анализ ТПО имеет недостаточную специфичность для дифференциальной диагностики фолликулярной карциномы и фолликулярной аденомы

Evaluation of an Australian Health Literacy Program Delivered in Adult Education Settings.

BACKGROUND: Adult education targeting health literacy (HL) may bring added value in the form of improved health. OBJECTIVE: This study evaluated the effects of a HL program as part of an adult education curriculum for adults with low literacy and numeracy. METHODS: This was a partial-cluster randomized controlled trial among 308 adults enrolled in basic education programs in Australia. Of the 308 participants, 141 (46%) were randomized to either the standard program (language, literacy, and numeracy [LLN]), or the HL intervention (LLN with embedded health content); the remainder (n = 167) were allocated to standard intervention programs by the education provider at the class level. The main outcomes were functional HL, self-reported confidence, patient activation, generic HL (ie, HLQ, health knowledge, and self-reported health behavior). Data were collected at baseline, immediately after, and at 6 months post-intervention. KEY RESULTS: Of the 308 participants, 71% had limited literacy and 60% spoke a language other than English at home. Both interventions benefited participants, with improvements from baseline to immediate follow up on individual-level functional HL (e.g., reading a thermometer; HL group 18.4% vs. standard group 7.2%; p = .001), confidence (HL group 0.34 vs. standard group 0.06; p = .014) and health literacy questionnaire (HLQ) subscales. At 6 months, improvements in confidence (p < .001) and some HLQ measures were retained. A consistent pattern of increased improvement in the HL program was observed compared to the standard program, although only some measures reached statistical significance: reading a food label (HL group 6.03/10 correct vs. standard group 5.49/10 correct; p = .022); confidence (p = .008); ability to actively manage health (HLQ) (p = .017), and health knowledge at 6 months (HL group 68% vs. standard group 60% correct, p = .052). HL participants reported being more likely to share course information and rated the program more useful to understand their health. CONCLUSIONS: Improving language, literacy, and numeracy generally has potential public health benefits that are retained at 6 months. Integrating health content adds further value to adult basic learning, is feasible, and potentially scalable. [HLRP: Health Literacy Research and Practice. 2019;3(Suppl.):S42-S57.]. PLAIN LANGUAGE SUMMARY: We compared the effect of an adult education-based health literacy (HL) program versus a standard language, literacy, and numeracy program on students' HL skills and psychosocial outcomes. Although students in both trial arms improved their skills, students in the HL program had better outcomes with higher HL, greater confidence, and higher health knowledge scores at 6 months

Choreography, controversy and child sex abuse: Theoretical reflections on a cultural criminological analysis of dance in a pop music video

This article was inspired by the controversy over claims of ‘pedophilia!!!!’ undertones and the ‘triggering’ of memories of childhood sexual abuse in some viewers by the dance performance featured in the music video for Sia’s ‘Elastic Heart’ (2015). The case is presented for acknowledging the hidden and/or overlooked presence of dance in social scientific theory and cultural studies and how these can enhance and advance cultural criminological research. Examples of how these insights have been used within other disciplinary frameworks to analyse and address child sex crime and sexual trauma are provided, and the argument is made that popular cultural texts such as dance in pop music videos should be regarded as significant in analysing and tracing public perceptions and epistemologies of crimes such as child sex abuse

COVID-19 Misinformation Trends in Australia: Prospective Longitudinal National Survey.

Background: Misinformation about COVID-19 is common and has been spreading rapidly across the globe through social media platforms and other information systems. Understanding what the public knows about COVID-19 and identifying beliefs based on misinformation can help shape effective public health communications to ensure efforts to reduce viral transmission are not undermined. Objective: This study aimed to investigate the prevalence and factors associated with COVID-19 misinformation in Australia and their changes over time. Methods: This prospective, longitudinal national survey was completed by adults (18 years and above) across April (n=4362), May (n=1882), and June (n=1369) 2020. Results: Stronger agreement with misinformation was associated with younger age, male gender, lower education level, and language other than English spoken at home (P<.01 for all). After controlling for these variables, misinformation beliefs were significantly associated (P<.001) with lower levels of digital health literacy, perceived threat of COVID-19, confidence in government, and trust in scientific institutions. Analyses of specific government-identified misinformation revealed 3 clusters: prevention (associated with male gender and younger age), causation (associated with lower education level and greater social disadvantage), and cure (associated with younger age). Lower institutional trust and greater rejection of official government accounts were associated with stronger agreement with COVID-19 misinformation. Conclusions: The findings of this study highlight important gaps in communication effectiveness, which must be addressed to ensure effective COVID-19 prevention

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

Authors’ Response to Peer Reviews of “The Psychological Impact of Hypertension During COVID-19 Restrictions: Retrospective Case-Control Study”

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