Discrimination of three mutational events that result in a disruption of the R122 primary autolysis site of the human cationic trypsinogen (PRSS1) by denaturing high performance liquid chromatography

BACKGROUND: R122, the primary autolysis site of the human cationic trypsinogen (PRSS1), constitutes an important "self-destruct" or "fail-safe" defensive mechanism against premature trypsin activation within the pancreas. Disruption of this site by a missense mutation, R122H, was found to cause hereditary pancreatitis. In addition to a c.365G>A (CGC>CAC) single nucleotide substitution, a c.365~366GC>AT (CGC>CAT) gene conversion event in exon 3 of PRSS1 was also found to result in a R122H mutation. This imposes a serious concern on the genotyping of pancreatitis by a widely used polymerase chain reaction-restriction fragment length polymorphism assay, which could only detect the commonest c.365G>A variant. MATERIALS AND METHODS: DNA samples containing either the known c.365G>A or c.365~366GC>AT variant in exon 3 of PRSS1 were used as positive controls to establish a denaturing high performance liquid chromatography (DHPLC) assay. RESULTS: DHPLC could readily discriminate the two known different mutational events resulting in the R122H mutation. More importantly, under the same experimental conditions, it identified a further mutational event that also occurs in the R122 primary autolysis site but results in a different amino acid substitution: c.364C>T (CGC>TGC; R122C). CONCLUSIONS: A rapid, simple, and low-cost assay for detecting both the known and new mutations occuring in the R122 primary autolysis site of PRSS1 was established. In addition, the newly found R122C variant represents a likely pancreatitis-predisposing mutation

Use of aviation by climate change researchers: Structural influences, personal attitudes, and information provision

Aviation is a fast-growing sector, releasing more carbon dioxide per passenger kilometre than other transport modes. For climate change researchers, work-related travel – including for conferences and fieldwork – is a major carbon-emitting activity. At the same time, many argue that climate scientists have an important role in curbing their own aviation emissions to align their practices with their assertions in relation to emissions reduction. We examine the tensions between competing professional demands in relation to flying; measure levels of flying by climate and non-climate researchers; assess influences on choices and attitudes; and consider how information provision and structural changes might enable changes in practice. Study 1 entails a large, international survey of flying undertaken by climate change (including sustainability and environmental science) researchers and those from other disciplines (N = 1408). Study 2 tests effects of varying information provision on researchers’ behavioural intentions and policy support to reduce flying (N = 362). Unexpectedly, we find climate change researchers – particularly professors – fly more than other researchers, but are also more likely to have taken steps to reduce or offset their flying. Providing information about the impacts of aviation increases behavioural intentions and support for institutional policies to reduce flying, particularly amongst more pro-environmental respondents. However, while attitudinal factors (e.g., personal norm) predict willingness to reduce flying, structural/social factors (e.g., family commitments, location) are more important in predicting actual flying behaviour. Recent initiatives to develop a low-carbon and more inclusive research culture within climate science and the broader research community thus need to be supported by broader policies and technologies to encourage and enable low-carbon and avoided travel

Deciphering why Salmonella Gallinarum is less invasive in vitro than Salmonella Enteritidis

International audienceSalmonella Gallinarum and Salmonella Enteritidis are genetically closely related however associated with different pathologies. Several studies have suggested that S. Gallinarum is less invasive in vitro than S. Enteritidis. In this study we confirm that the S. Gallinarum strains tested were much less invasive than the S. Enteritidis strains tested in cells of avian or human origin. In addition, the S. Gallinarum T3SS-1-dependent ability to invade host cells was delayed by two to three hours compared to S. Enteritidis, indicating that T3SS-1-dependent entry is less efficient in S. Gallinarum than S. Enteritidis. This was neither due to a decreased transcription of T3SS-1 related genes when bacteria come into contact with cells, as transcription of hilA, invF and sipA was similar to that observed for S. Enteritidis, nor to a lack of functionality of the S. Gallinarum T3SS-1 apparatus as this apparatus was able to secrete and translocate effector proteins into host cells. In contrast, genome comparison of four S. Gallinarum and two S. Enteritidis strains revealed that all S. Gallinarum genomes displayed the same point mutations in each of the main T3SS-1 effector genes sipA, sopE, sopE2, sopD and sopA

ESVM Guideline on peripheral arterial disease

International audienc

LIMPRINT: a sociological perspective on "chronic edema"

Background: Chronic edema is a condition that is biologically complex, distressing for patients and sociopolitically weak. Like many other complex and chronic conditions, it has a low status within health care. The result is that it has a low priority in health policy and consequently is undervalued and undertreated. While evidence-based practice promotes a hierarchy of evidence, it is also the case that clinical practice is influenced by a hierarchy of social status. These are as much political as they are scientific. Methods and Results: This article will provide an explanation for why chronic edema is a low priority. It will do this through a critical review of the literature. We examine this through the theoretical lens of Pierre Bourdieu. The sociology of Bourdieu frames an understanding of power relations through habitus, field, and capital. We will employ these theoretical tools to understand the way that chronic edema is situated within the policy arena. We identify a number of social mechanisms that affect the status of chronic edema, including diagnostic uncertainty, social capital, scientific capital, cultural capital and economic capital. Conclusion: We argue that a whole system approach to care, based on human need rather than unequal power relations, is a prerequisite for the delivery of good health care. The specialty of chronic edema is not a powerless group and we identify some of the ways that the social mechanism that acts as barriers to change, can also be employed to challenge them. Methods: This paper will provide an explanation for why chronic oedema is a low priority. It will do this through a critical review of the literature. We examine this through the theoretical lens of Pierre Bourdieu. The sociology of Bourdieu frames an understanding of power relations through habitus, field and capital. We will employ these theoretical tools to understand the way that chronic oedema is situated within the policy arena

Prevalence and risk factors for chronic edema in U.K. community nursing services

Background and study design: Chronic edema (CO) is believed to be a major clinical problem within community nursing services in the UK. This study was undertaken as part of the LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Methods and Results: Three urban based community nursing services participated in the UK with prospective evaluation over 4 weeks of all patients receiving nursing care using a questionnaire-based interview and clinical assessment using the LIMPRINT tools. Of the total 2,541 assessed 1,440 (56.7%) were considered to have CO, comprising Leicester City (768/ 1298 (59.2%), Nottingham West (124/ 181 (68.5%)) and Nottingham City (548/1062 (51.6%)). The mean age for women with CO was 78.6 (SD 12.8) years and for men 72.9 (SD14.5). More patients with CO suffered from diabetes (32.1% versus 27.9%, p=0.027), heart failure/ ischaemic heart disease (27.3% versus 14.0%, p<0.001) and peripheral arterial occlusive disease (5.5% versus 1.9%, p<0.001). By far the greatest association was with the presence of a wound (73.6% versus 37.9%, p<0.001). Cellulitis affected 628 (24.7%) and 688 (47.8%) had a concurrent leg ulcer. Rates of reduced mobility (71.6% versus 61.9%) and obesity were higher in those with CO. Six independent factors associated with chronic oedema were service location, age, ethnicity, obesity, heart failure and the presence of a wound. Conclusion: Chronic oedema is a major and growing health care problem within primary care that has been previously unrecognised and requires effective service provision

A study to explore the parental impact and challenges of self-management in children and adolescents with lymphedema

Background: Limited research has shown the impact lymphedema has on children and families. The aim of this study was to explore the parental experience of caring for a child or adolescent with lymphedema and the daily challenges of self-management and self-efficacy. Methods and Results: Participants were recruited during an educational camp for children with lymphedema (N = 26). Three individual semistructured focus groups were undertaken in English, French, and Italian with simultaneous translation. Data were analyzed using interpretative phenomenological analysis. Analysis identified four superordinate themes; the journey, treatment management, independence, and psychosocial impact. Ten subthemes were identified: bandaging/compression, professional support, holistic care, fear, self-efficacy, acceptance, friendship, guilt, distress, and hope. Conclusions: Parental self-management of children with lymphedema is complex and invades many aspects of life. Lack of professional agreement over what constitutes self-management leads to parental confusion and anxiety. Self-management is demanding, and parents are ambivalent to its effectiveness, but choose to persevere through fear of their child's condition deteriorating. Self-efficacy is evident in complex problem solving, despite parents believing that they are not adequately prepared for this

LIMPRINT: the UK experience - subjective control of swelling in patients attending specialist lymphedema services

Background and study design: This study was undertaken as part of the UK LIMPRINT international study to determine the number of people with chronic oedema and its impact on health services. Overall 7436 with chronic oedema (CO) were recruited in the main UK study from a range of health settings. Methods and results: Subjective control of arm and leg chronic oedema (CO) was defined for patients attending three Lymphoedema services in the UK. Of the total available in the UK dataset 5165 (69.4%)/ 7436(100%) of participants were included. Reasons for exclusions included the following: lack of information (1669), having both arm and leg swelling (272), lack of description of control (5) and professional inability to decide whether CO was controlled (325). Arm swelling occurred in 953 (18.5%), with leg CO in 4212 (81.5%). Poor control was found in 1430 (27.7%) and good control in 3735 (72.3%). Control of arm swelling was worse in men and control increased overall in those aged over 45 years. In contrast control of CO worsened in those with leg CO with increasing age and multiple co-morbidities. Obesity and cellulitis, particularly an episode in the last year were associated with poor control. Independent risk factors for arm CO were obesity, neurological disease and cellulitis in the last year and for leg CO: obesity, poor mobility, heart disease, presence of a wound, cellulitis in the last year and duration of swelling. Conclusion: Control of CO within specialised centres is complex due to sociodemographic and clinical comorbidities

Estimation of the prevalence of lymphoedema/chronic oedema in acute hospital in-patients

Background: To estimate the prevalence of lymphoedema/chronic oedema and wounds in acute hospital in-patients in 5 different countries. Method: A point-prevalence study was carried out during working day periods in six general hospitals in four countries (Denmark, France, United Kingdom, Australia) and one hospital oncology in-patient unit in one other country (Ireland). The study used validated clinical tools for the assessment and collection of data. Data were collected by expert clinicians through interviews and physical examination of the patients present in the wards. Results: A total of 1905 patients could be included and investigated among the 3041 total bed occupancy in the seven hospitals. Lymphoedema/chronic oedema was present in 723 of them (38%). Main risk factors associated with chronic oedema were age, morbid obesity and heart failure as well as chair bound immobility and neurological deficiency. History of cellulitis was frequent in patients with chronic oedema and wounds (24.8%), chronic oedema alone (14.1%) as compared to the 1.5% prevalence in patients without chronic oedema. Conclusion: Lymphoedema/chronic oedema is very frequent in patients hospitalized in hospital acute wards. It is strongly associated with obesity, venous insufficiency and heart failure. Our results strongly suggest a hidden health care burden and cost linked to chronic oedema independently of chronic wounds

COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

Coronavirus disease 2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy. Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease. Herein, we review the current understanding of the pathogenesis, epidemiology, management and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, and of those with preexisting thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/1/Bikdeli-2020-COVID-19 and Thrombotic or Thromb.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/3/DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID_Barnes.docxhttps://deepblue.lib.umich.edu/bitstream/2027.42/155446/4/license_rdf.rdfDescription of Bikdeli-2020-COVID-19 and Thrombotic or Thromb.pdf : ArticleDescription of DeepBluepermissions_agreement-CCBYandCCBY-NC_ORCID_Barnes.docx : Deep Blue sharing agreemen