Emerging role of endosomal toll-like receptors in rheumatoid arthritis

Toll-like receptors (TLRs) and their downstream signaling pathways have been comprehensively characterized in innate immunity. In addition to this function, these receptors have also been suggested to be involved in the pathogenesis of many autoimmune diseases, including rheumatoid arthritis (RA). Murine in vivo models and human in vitro tissue models of RA have provided a wealth of information on the potential activity of TLRs and components of the downstream signaling pathways. Whilst most early work investigated the cell surface TLRs, more recently the focus has moved to the endosomal TLRs 3, 7, 8, and 9. These receptors recognize self and foreign double-stranded RNA and single-stranded RNA and DNA. The development of therapeutics to inhibit the endosomal TLRs or components of their signaling cascades may represent a way to target inflammation upstream of cytokine production. This may allow for greater specificity than existing therapies including cytokine blockade. Here, we review the current information suggesting a role for the endosomal TLRs in RA pathogenesis and the efforts to target these receptors therapeutically

Managing Financial Reports of Commercial Banks

This paper investigates the extent to which banks alter the timing and magnitude of transactions such as asset sales, loan loss accruals, pension settlements and securities issues in response to primary capital, tax, and earnings goals. The authors hypothesize that each year bank managers face a cost minimization problem that encompasses the costs of deviating from primary capital, tax, and earnings goals, as well as the costs of exercising discretion over loan loss accruals, transactions such as asset sales, and securi-ties issues. The authors construct a system of five equations, one for the optimal level of each of the items over which the manager can exercise discretions to achieve the three goals. The authors find that loan charge-offs, loan loss provisions, and the decision to issue securities are jointly determined, apparently to manage primary capital ratios. The research suggests that pension settlement gains are determined independently of the other four decisions, and appear to be used to manage end-of-period earnings. Miscellaneous gains (losses) are used primarily to manage earnings; but weaker evidences suggests that they are also used to manage capital. The authors find broad support for the hypotheses that deviating from capital and earnings goals is costly, and that bank managers trade-off costly accrual and financing discretion to meet these goals. The policy implications of this recent research are intriguing. For example, mark-to-market rules that limit the manager's ability to strategically time gains from sales of securities may simply induce the manager to substitute an alternative form of discretion - delaying or accelerating charge-offs and loan loss provisions. The framework and evidence support the notion that accrual, investment, and financing decisions are not independent. In the context of contracting and monitoring motivations for accounting choices, this means that focusing solely on the accounting systems's role in mitigating these costs potentially omits important correlated factors.

Toward a Transformative Education within Youth Media Production

Review of: Jocson, Korina M. Youth Media Matters: Participatory Cultures and Literacies in Education. U of Minnesota P, 2018.   DOI: 10.1353/jeu.2020.001

The Exchange Rate Exposure of U.S. and Japanese Banking Institutions

In this paper, we examine the foreign exchange exposure of a sample of U. S. and Japanese banking firms. Using daily data, we construct estimates of the exchange rate sensitivity of the equity returns of the U.S. bank holding companies and compare them to those of the Japanese banks. We find that the stock returns of a significant fraction of the U. S. companies move with the exchange rate, while few of the Japanese returns that we observe do so. We next examine more closely the sensitivity of the U.S. firms by linking the U.S. estimates cross-sectionally to accounting-based measures of currency risk. We suggest that the sensitivity estimates can provide a benchmark for assessing the adequacy of existing accounting measures of currency risk. Benchmarked in this way, the reported measures that we examine appear to provide a significant, though only partial, picture of the exchange rate exposure of U. S. banking institutions. The cross-sectional evidence is also consistent with the use of foreign exchange contracts for the purpose of hedging.Foreign Exchange Risk, Banking, Market Risk

Supporting Professional Development Through MOOCs: the TESSA Experience

Policy aspirations for education across sub - Saharan Africa are requiring teachers to change from being transmitters of knowledge to facilitators of learning. This means that teacher education needs to change as well. At present, teacher preparation courses are highly theoretical, and many teacher educators have very limited sch ool teaching experience. Teacher Education in sub - Saharan Africa (TESSA), open educational resources (OER) can support teacher educators in developing the practical knowledge needed, yet many see them as resources for teachers rather than themselves. Also, curricula and examination systems may restrict the incorporation of OER into teacher preparation programmes. The TESSA MOOC - Making teacher education relevant for 21 st Century Africa - was designed to support teacher educators in changing their practice and better support teachers in the new curricula being developed. It focused on active teaching approaches, incorporating ICT into classroom learning, and using TESSA materials and other OER. It ran three times, over two years, and nearly 7000 participants , mainly from sub - Saharan Africa (SSA), registered. For many people it was their first experience of online learning. They studied on phones, in environments where electricity and connectivity were erratic, and supported each other in local communities. De spite the challenges, the completion rates for the first two presentations were encouragingly high compared with the norm for MOOCs. This paper analyses data from the pre - and post - course surveys from the first two presentations to understand who took pa rt, how they studied, what they learnt and how it has impacted on their practice

Structural modification of the antidepressant mianserin suggests that its anti-inflammatory activity may be independent of 5-Hydroxytryptamine receptors

Antidepressants are increasingly recognized to have anti-inflammatory properties in addition to their ability to treat major depressive disorders. To explore if engagement of 5-hydroxytryptamine (5-HT) receptors was required for the anti-inflammatory effect of the tetracyclic antidepressant mianserin, a series of structural derivatives were generated with the aim of reducing 5-HT receptor binding. Primary human peripheral blood mononuclear cells were used to screen for anti-inflammatory activity. The lead compound demonstrated a significant loss in 5-HT receptor binding, as assessed by non-selective 5-HT binding of radiolabelled serotonin in rat cerebral cortex. However, it retained the ability to inhibit endosomal toll-like receptor 8 signaling in primary human macrophages and spontaneous cytokine production from human rheumatoid synovial tissue equivalent to that previously observed for mianserin. These data demonstrate that the anti-inflammatory mechanism of mianserin may be independent of 5-HT receptor activity. This research offers new insights into the mechanism and structural requirements for the anti-inflammatory action of mianserin

Family-centred interventions by primary healthcare services for Indigenous early childhood wellbeing in Australia, Canada, New Zealand and the United States: a systematic scoping review

Background: Primary healthcare services in Australia, Canada, New Zealand and the United States have embraced the concept of family-centred care as a promising approach to supporting and caring for the health of young Indigenous children and their families. This scoping review assesses the quality of the evidence base and identifies the published literature on family- centred interventions for Indigenous early childhood wellbeing. Methods: Fourteen electronic databases, grey literature sources and the reference lists of Indigenous maternal and child health reviews were searched to identify relevant publications from 2000 to 2015. Studies were included if the intervention was: 1) focussed on Indigenous children aged from conception to 5 years from the abovementioned countries; 2) led by a primary healthcare service; 3) described or evaluated; and 4) scored greater than 50% against a validated scale for family-centredness. The study characteristics were extracted and quality rated. Reported aims, strategies, enablers and outcomes of family-centredcare were identified using grounded theory methods. Results: Eighteen studies (reported in 25 publications) were included. Three were randomised controlled studies; most were qualitative and exploratory in design. More than half of the publications were published from 2012 to 2015. The overarching aim of interventions was to promote healthy families. Six key strategies were to: support family behaviours and self- care, increase maternal knowledge, strengthen links with the clinic, build the Indigenous workforce, promote cultural/ community connectedness and advocate for social determinants of health. Four enablers were: competent and compassionate program deliverers, flexibility of access, continuity and integration of healthcare, and culturally supportive care. Health outcomes were reported for Indigenous children (nutritional status; emotional/behavioural; and prevention of injury and illness); parents/caregivers (depression and substance abuse; and parenting knowledge, confidence and skills); health services (satisfaction; access, utilization and cost) and community/cultural revitalisation. Discussion and conclusion: The evidence for family-centred interventions is in the early stages of development, but suggests promise for generating diverse healthcare outcomes for Indigenous children and their parents/caregivers, as well as satisfaction with and utilisation of healthcare, and community/cultural revitalisation. Further research pertaining to the role of fathers in family-centred care, and the effects and costs of interventions is needed

TLR1/2 and 5 induce elevated cytokine levels from rheumatoid arthritis monocytes independent of ACPA or RF autoantibody status

Objective RA is an autoimmune inflammatory joint disease. Both RF and ACPA are associated with more progressive disease and higher levels of systemic inflammation. Monocyte activation of toll-like receptors (TLRs) by endogenous ligands is a potential source of increased production of systemic cytokines. RA monocytes have elevated TLRs, some of which are associated with the disease activity score using 28 joints (DAS28). The aim of this study was to measure TLR-induced cytokine production from monocytes, stratified by autoantibody status, to assess if their capacity to induce cytokines is related to autoantibody status or DAS28. Methods Peripheral blood monocytes isolated from RA patients and healthy controls were stimulated with TLR1/2, TLR2/6, TLR4, TLR5, TLR7, TLR8 and TLR9 ligands for 18 h before measuring IL-6, TNFα and IL-10. Serum was used to confirm the autoantibody status. Cytokine levels were compared with RF, ACPA and DAS28. Results RA monocytes demonstrated significantly increased IL-6 and TNFα upon TLR1/2 stimulation and IL-6 and IL-10 upon TLR5 activation. TLR7 and TLR9 activation did not induce cytokines and no significant differences were observed between RA and healthy control monocytes upon TLR2/6, TLR4 or TLR8 activation. When stratified by ACPA or RF status there were no correlations between autoantibody status and elevated cytokine levels. However, TLR1/2-induced IL-6 did correlate with DAS28. Conclusions Elevated TLR-induced cytokines in RA monocytes were not related to ACPA or RF status. However, TLR1/2-induced IL-6 was associated with disease activity

Professional development in the digital age: supporting improvements in teacher education through MOOCs

Education policies across sub-Saharan Africa require teachers to change from being transmitters of knowledge to facilitators of learning. This means that teacher education needs to change as well and professional development which focuses on practical teaching is urgently needed. The Teacher Education for sub-Saharan Africa (TESSA) MOOC - Making teacher education relevant for 21st Century Africa - was designed to support teacher educators in changing their practice. The MOOC modelled socio-cultural theories of learning and focused on issues identified by the TESSA network. It ran four times, over two years, and nearly 9000 participants, mainly from sub-Saharan Africa (SSA), registered. For many it was their first experience of online learning. They studied on phones, in environments where electricity and connectivity were erratic, and supported each other in local communities. We draw on survey data from the first two presentations and in-depth interviews with four MOOC graduates to understand who took part, how they studied, what they learnt and how it has impacted on their practice and professional identity. For some individuals the experience was transformational. The study highlights the potential of this form of professional development, to make a difference particularly in a policy environment which is seeking pedagogic change

Paths to improving postpartum care among Australian Aboriginal and Torres Strait Islander women after gestational diabetes

Background: Indigenous women in far north Queensland are less likely than non-Indigenous women to present for post-partum screening after gestational diabetes mellitus (GDM) despite a fourfold increased risk of type 2 diabetes within eight years of the pregnancy. Aim: To understand barriers and enablers to post-natal follow-up. Methods: We conducted interviews with Indigenous women with previous GDM, focus groups with Indigenous healthworkers and workshops with other health professionals. Data collection included brainstorming, visualisation, sorting and prioritising activities. Data was analysed thematically using the Theoretical Domains Framework. Barriers are presented under the headings of 'capability', 'motivation' and 'opportunity'. Enabling strategies are presented under 'intervention' and 'policy' headings. Results: Participants generated twenty-eight enabling environmental, educational and incentive interventions, and service provision, communication, guideline, persuasive and fiscal policies to address barriers to screening and improve postpartum support for women. The highest priorities included providing holistic social support, culturally appropriate resources, improving Indigenous workforce involvement and establishing structured follow-up systems. Conclusions: Understanding Indigenous women's perspectives, developing strategies with healthworkers, and action planning with other health professionals can generate context-relevant feasible strategies to improve postpartum care after GDM. However, we need to better understand how to effectively support Indigenous women and communities during the postpartum period