The Function of Heat Shock Protein 27 in Interleukin-1 Signalling

The p38 mitogen activated protein kinase (MAPK) pathway enhances the expression of proinflammatory response genes, including cyclooxgenase (COX)-2 and interleukin (IL)-6 in response to stimuli including IL-1. Heat shock protein 27 (HSP27) is a major protein phosphorylated by MAPK activated protein kinase 2 (MK2), a downstream kinase of p38 MAPK. However, the role of HSP27 in inflammation is unclear. Previous work has shown the requirement of HSP27 for stabilisation of COX-2 and IL-6 mRNAs following IL-1 treatment of HeLa cells. To examine the role of HSP27 in IL-1 signalling I depleted the protein from HeLa cells, human alveolar epithelial (A549) cells and human dermal fibroblasts (HDFs) by RNA interference (RNAi) using multiple short interfering RNAs (siRNAs). HSP27 suppression in HeLa cells inhibited IL-1 induced activation of MK2, p38 MAPK and c-Jun N-terminal kinase (JNK), but not extracellular signal-regulated kinase (ERK). Upstream MAPK kinase (MKK) 3, 4, 6 and 7 and TGF-beta-activated kinase 1 (TAK1) were also inhibited. HSP27 depletion did not disrupt the constitutive interaction found between TAK1 and its binding protein TAB1. HSP27 appeared to impinge on signalling at a point lying between cell surface receptors and TAK1 or at TAK1 itself as activation of JNK and p38 MAPK by tumour necrosis factor (TNF) was inhibited by HSP27 knockdown. A transfection procedure was developed for transfection of siRNA into HDF cells. In HDFs and A549 cell types HSP27 was required for COX-2 protein expression and the full activation of p38 MAPK. However, while TAK1 was shown to be responsible for sustained activation of p38 MAPK, TAK1 activity was not affected by HSP27 depletion in HDFs. MKK3 (rather than MKK6) appeared to be the major HDF activator of p38 MAPK in response to IL-1. My results demonstrate that HSP27 has a novel role in augmenting IL-1 signalling in epithelial cell lines and fibroblasts

How do Listeners Form Grammatical Expectations to African American Language?

Ideologies about standard language in the United States often posit Mainstream U.S. English (MUSE) as a morally superior variety (Hill 2008). Previous research has shown that this kind of hierarchical treatment of language varieties leads to negative perceptions of non-standard languages, which in turn makes them stigmatized, and ultimately perpetuates dialect discrimination. This kind of discrimination results in the mistreatment of users of non-standard varieties, which negatively affects the way those speakers can move through the U.S. context (Rickford 1999, Eckert and Rickford 2001, Schilling 2004, Rickford and King 2016). This study investigates how listeners alter their linguistic expectations when hearing speakers of standard and non-standard varieties of English through an Electroencephalography (EEG) experiment. We probe how social information influences syntactic processing to see if and when speakers of a standard dialect, MUSE, form grammatical expectations when processing MUSE and African American Language (AAL). Looking at online processing helps us better understand whether listeners have specific knowledge of the dialect that is not their own (dialect-specific hypothesis), or whether listeners more generally reduce expectations across the board when listening to a dialect or variant that they themselves do not speak (dialect non-specific hypothesis). In order to test the interaction between language variety and auxiliary usage, experimental sentences were constructed in order to reflect a variant that is grammatical in MUSE, a variant that is grammatical uniquely to AAL, and a grammatical variant that is ungrammatical in all varieties of English. The experimental stimuli from a bidialectal Midwestern black speaker of both MUSE and AAL, yielding a within subject 2 (language varieties) by 3 (grammatical features) design. The results do not cleanly favor the dialect-specific nor the dialect non-specific hypothesis. Rather, the evidence points a nuanced version of a mixture of both hypotheses. Through analysis of American English dialects, this work contributes to further understanding of how social information interfaces with online processing, and expectations that may be formed depending on the perceived identity of a voice. The impact of this work is paramount, as perceptions of stigmatized language varieties can lead to dialect discrimination that negatively affects the way those speakers are treated (Rickford 1999, Purnell, Baugh, Idsardi 1999, Eckert and Rickford 2001, Schilling 2004, Rickford and King 2016

Ryanodine receptors, a family of intracellular calcium ion channels, are expressed throughout early vertebrate development

<p>Abstract</p> <p>Background</p> <p>Calcium signals ([Ca²⁺]_i) direct many aspects of embryo development but their regulation is not well characterised. Ryanodine receptors (RyRs) are a family of intracellular Ca²⁺release channels that control the flux of Ca²⁺from internal stores into the cytosol. RyRs are primarily known for their role in excitation-contraction coupling in adult striated muscle and <it>ryr </it>gene mutations are implicated in several human diseases. Current evidence suggests that RyRs do not have a major role to play prior to organogenesis but regulate tissue differentiation.</p> <p>Findings</p> <p>The sequences of the five zebrafish <it>ryr </it>genes were confirmed, their evolutionary relationship established and the primary sequences compared to other vertebrates, including humans. RyRs are differentially expressed in slow (<it>ryr1a</it>), fast (<it>ryr3</it>) and both types (<it>ryr1b</it>) of developing skeletal muscle. There are two <it>ryr2 </it>genes (<it>ryr2a </it>and <it>ryr2b</it>) which are expressed exclusively in developing CNS and cardiac tissue, respectively. In addition, <it>ryr3 </it>and <it>ryr2a </it>mRNA is detectable in the initial stages of development, prior to embryonic axis formation.</p> <p>Conclusions</p> <p>Our work reveals that zebrafish <it>ryr </it>genes are differentially expressed throughout the developing embryo from cleavage onwards. The data suggests that RyR-regulated Ca²⁺signals are associated with several aspects of embryonic development, from organogenesis through to the differentiation of the musculoskeletal, cardiovascular and nervous system. These studies will facilitate further work to explore the developmental function of RyRs in each of these tissue types.</p

Investigation of Emergency Department Visits and Hospitalization Rates of Child Physical Abuse at Cooper University Hospital Prior to and During the COVID-19 Pandemic

The COVID-19 pandemic has been detrimental for children. Many families have experienced stressors, including unemployment, financial hardship, and familial illness. These factors all pose increased risk for child physical abuse. Limitations in child welfare services affected investigations and provision of services to high-risk families. The extent to which the rates of physical abuse in NJ have been affected is unknown. We sought to answer the question of whether the COVID-19 pandemic affected the severity of physical abuse and the incidence of physical abuse presenting to Cooper University Hospital. We hypothesized that there would be a higher proportion of severe child physical abuse cases presenting to the hospital during the COVID-19 pandemic as compared to prior to the pandemic

“I always feel like I have to rush…”: pet owner and small animal veterinary surgeons’ reflections on time during preventative healthcare consultations in the United Kingdom

Canine and feline preventative healthcare consultations can be more complex than other consultation types, but they are typically not allocated additional time in the United Kingdom (UK). Impacts of the perceived length of UK preventative healthcare consultations have not previously been described. The aim of this novel study was to provide the first qualitative description of owner and veterinary surgeon reflections on time during preventative healthcare consultations. Semi-structured telephone interviews were conducted with 14 veterinary surgeons and 15 owners about all aspects of canine and feline preventative healthcare consultations. These qualitative data were thematically analysed, and four key themes identified. This paper describes the theme relating to time and consultation length. Patient, owner, veterinary surgeon and practice variables were recalled to impact the actual, versus allocated, length of a preventative healthcare consultation. Preventative healthcare consultations involving young, old and multi-morbid animals and new veterinary surgeon-owner partnerships appear particularly susceptible to time pressures. Owners and veterinary surgeons recalled rushing and minimizing discussions to keep consultations within their allocated time. The impact of the pace, content and duration of a preventative healthcare consultation may be influential factors in consultation satisfaction. These interviews provide an important insight into the complex nature of preventative healthcare consultations and the behaviour of participants under different perceived time pressures. These data may be of interest and relevance to all stakeholders in dog and cat preventative healthcare

Investigating preventive-medicine consultations in first-opinion small-animal practice in the United Kingdom using direct observation

Preventive-medicine consultations account for a large proportion of the veterinary caseload and previous research has suggested these consultations are fundamentally different from those in which the animal is presented for a specific health problem. There has been recent controversy around some aspects of preventive medicine for cats and dogs, and the full health benefits of the preventive-medicine consultation remain unclear. The aim of this study was to compare characteristics of the consultation and the problems discussed during the consultation between preventive-medicine consultations and other types of consultations. Data were gathered during direct observation of small-animal consultations in seven first-opinion practices in the United Kingdom. Data collected included type of clinical examination performed, patient signalment, and details of all problems discussed (including whether the problem was presenting or non-presenting, new or pre-existing, who had raised the problem, body system affected and whether an action was taken). A two-level multivariable logistic-regression model was developed, with canine and feline patients at Level 1 nested within consulting veterinary surgeons at Level 2, and a binary outcome variable of preventive-medicine consultation versus specific health-problem consultation. A total of 1807 patients were presented, of which 690 (38.2%) presented for a preventive-medicine consultation. Dogs were the most frequently presented species (n = 1168; 64.6%) followed by cats (n = 510; 28.2%), rabbits (n = 86; 4.8%) and patients of other species (n = 43; 2.4%). The five variables remaining in the multi-level model were whether multiple patients were presented, patient age, clinical examination type, weighing and number of problems discussed. Species, breed, sex, neutering status and practice did not remain in the final model. Many non-presenting problems, including both preventive-medicine problems and specific-health problems, were discussed and acted upon during all types of consultations. Dental and behavioural non-presenting problems were discussed more frequently during preventive-medicine consultations compared with specific health-problem consultations. Preventive-medicine consultations represent an opportunity for veterinary surgeons to discuss other aspects of preventive medicine, and to detect and manage new and ongoing health problems. A greater evidence base is needed to understand whether detecting and managing underlying disease during the preventive-medicine consultation has a positive impact on lifelong patient health and welfare

Diagnostic testing in first opinion small animal consultations

DIAGNOSTIC testing is a vital part of the decision-making process, which aims to increase diagnostic certainty, assist management and treatment decisions and provide a prognosis (Radostits and others 2000). A wide range of tests are available, with variable accuracy, expense and risk to the patient, but it is currently unclear how veterinary surgeons are making decisions about which tests to carry out. Understanding the decision-making process is vital in order to ensure that the decisions made during the consultation are based on the best relevant evidence. However, before decision-making around diagnostic testing can be understood, it is neccessary to know which tests are performed most frequently. This may be useful for veterinary practices, for example, when making business decisions surrounding diagnostic equipment and in-house training, and could also help direct veterinary curricula and research. The aim of this study was to describe the diagnostic tests commonly performed in a convenience sample of first opinion small animal consultations. Data collection took place over 16 weeks (two weeks each in eight different practices) as part of data gathered for a larger project (Robinson and others 2014a). A previously developed data collection tool (Robinson and others 2014a) was used to record consultation data by direct observation. Data were recorded on all health problems discussed, including the reason for presentation (the presenting problem) and all additional problems discussed (non-presenting problems). For each health problem discussed, the type of diagnostic test(s) was recorded by selecting one option from: None; In-consultation; Post-consultation; Both. Clinical examination, as defined by Robinson and others (2014b), was not considered to be a diagnostic

Measuring the success of canine and feline preventative healthcare consultations: a systematic review

Preventative healthcare consultations account for a large proportion of the veterinary caseload. This novel study is the first to methodically review all literature on canine and feline preventative healthcare consultations. Previous research has found these consultations to be different from health problem consultations in terms of communication style and content. Identifying relevant evidence and previously validated methods of measuring the success of these consultations will be useful when implementing strategies for optimisation. The aim of this study was to identify and assess the quality of existing literature which describes and/or measures the success of preventative healthcare consultations.Database searches of CAB Abstracts and Medline were conducted to identify published literature. Google searches were then conducted to identify any additional published or grey literature. Results were systematically screened to determine whether the returned sources were about cats and/or dogs, whether they related to preventative healthcare, and whether they described and/or measured the success of preventative healthcare consultations. For primary research citations which only described preventative healthcare consultations, data were extracted on the aspects of the consultations described. For citations which additionally measured the success of the consultations, the measures used, sampling technique, key results and key weaknesses were also extracted. Of 17538 citations identified in total during the database searches, a total of seven relevant primary research citations were identified. All of these citations described aspects of the preventative healthcare consultation, such as consultation length, health problems discussed, actions taken and communication style. Only one primary research citation measured success of the consultation, using veterinarian satisfaction to determine success. In addition, 30 narrative citations, including expert opinion pieces, textbooks, guidelines without transparent methodology and conference presentations were identified. Google searches identified 224 relevant narrative citations, and five of the seven primary research citations identified by the database searches, but did not identify any additional relevant primary research citations. The results suggest that, despite accounting for around a third of all consultations, there is relatively little evidence describing preventative healthcare consultations and only one measure of success has been described for these consultations. This presents potential challenges when implementing strategies to optimise these consultations, as measures which are useful and relevant to veterinary practice should first be identified. Identifying useful measures of success will allow future strategies designed to maximise the benefits of these consultations to be meaningfully assessed for efficacy