• Regucalcin ameliorates Doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria

      Mohammed, Noor A; Hakeem, Israa; Hodges, Nikolas J; Michelangeli, Francesco (Portland Press Ltd., 2021-12-14)
      Doxorubicin (DOX) is a potent anti-cancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 hours over a range of concentrations and the LC50 was determined to be 7µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 hours, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically-induced cell stress.
    • Regucalcin ameliorates doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria

      Mohammed, Noor A.; Hakeem, Israa J.; Hodges, Nikolas; Michelangeli, Francesco; orcid: 0000-0002-4878-046X (Portland Press Ltd., 2022-01-06)
      Abstract Doxorubicin (DOX) is a potent anticancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 h over a range of concentrations, and the LC50 was determined to be 7 µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 h, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically induced cell stress.
    • Regucalcin ameliorates Doxorubicin-induced cytotoxicity in Cos-7 kidney cells and translocates from the nucleus to the mitochondria.

      Mohammed, Noor A; Hakeem, Israa; Hodges, Nikolas J; Michelangeli, Francesco (2021-12-14)
      Doxorubicin (DOX) is a potent anti-cancer drug, which can have unwanted side-effects such as cardiac and kidney toxicity. A detailed investigation was undertaken of the acute cytotoxic mechanisms of DOX on kidney cells, using Cos-7 cells as kidney cell model. Cos-7 cells were exposed to DOX for a period of 24 hours over a range of concentrations and the LC50 was determined to be 7µM. Further investigations showed that cell death was mainly via apoptosis involving Ca2+ and caspase 9, in addition to autophagy. Regucalcin (RGN), a cytoprotective protein found mainly in liver and kidney tissues, was overexpressed in Cos-7 cells and shown to protect against DOX-induced cell death. Subcellular localization studies in Cos-7 cells showed RGN to be strongly correlated with the nucleus. However, upon treatment with DOX for 4 hours, which induced membrane blebbing in some cells, the localization appeared to be correlated more with the mitochondria in these cells. It is yet to be determined whether this translocation is part of the cytoprotective mechanism or a consequence of chemically-induced cell stress. [Abstract copyright: Copyright 2021 The Author(s).]
    • Regulating patient safety during hospital discharges: Casting the Patient Safety Commissioner as the Representative of Order

      Moore, Victoria L.; orcid: 0000-0002-1349-3612; email: victoria.moore@manchester.ac.uk (SAGE Publications, 2021-06-11)
      This article examines the challenges in regulating patient safety during hospital discharges in England through the lens of liminality. Hospital discharges are internationally recognised as being a dangerous time for patients, and yet the role that regulators should play in addressing this has received little attention in any jurisdiction. Liminality’s spotlight on the in-between highlights how the discharge process can give rise to patient safety incidents that fall between regulator’s boundaries. Falling between boundaries results in a dearth of effective regulatory responses to address these incidents. By positioning the new role of Patient Safety Commissioner (PSC) as that of a ‘Representative of Order’, this article proposes a means by which this poorly regulated space could be navigated more successfully. This analysis suggests that the remit of the PSC role be expanded to include improving patient safety with regard to processes – not just medicines and medical devices. The full implications of this are also addressed.
    • Reid Bryson: The crisis climatologist

      Naylor, Robert Luke; orcid: 0000-0002-9585-9939; email: robert.naylor-4@postgrad.manchester.ac.uk (John Wiley & Sons, Inc., 2021-10-25)
      Abstract: Reid Allen Bryson (1920–2008) was a forceful orator who consistently fought against institutional pressures to get his messages out to the public. In the 1960s, Bryson was a leader in the wider academic turn toward politically charged interdisciplinarianism. To the dismay of many of his colleagues, he publicly made climatological prognoses in the 1970s, becoming a significant figure in the media landscape. He was not swayed by the arguments for global warming, even as the framing became the recognized face of climate change in the late 1980s. By examining the controversies that Bryson instigated and the currents that he swam against, we can see the wider community crystallizing and promoting positions that may have previously gone unstated. In addition, Bryson's personal contribution to the rise of climate discourse has been underexplored in the historical literature. Bryson was instrumental in bringing climate onto the political radar during the World Food Crisis of 1973, shocking both the US and Canadian political establishments into paying more attention to the issue. Bryson's narrative linking climate change to both food supply and a series of climate anomalies in the 1970s remained predominant in the first World Climate Conference of 1979. Bryson also helped break a seal on climatologists speaking directly to the media, leading to unprecedented climate discourse in the 1970s and giving climate change a springboard to become one of the defining issues of the 21st century. This article is categorized under: Climate, History, Society, Culture > Thought Leaders
    • Reimagining climate‐informed development: From “matters of fact” to “matters of care”

      Tozzi, Arianna; orcid: 0000-0002-7639-0178; email: arianna.tozzi@postgrad.manchester.ac.uk (2021-06-03)
      This paper is concerned with the impasse climate‐informed development practices currently find themselves in. This is represented by the fact that while “solutions” to reduce vulnerabilities and enhance capacities for adaptation and resilience are increasingly adopted around the world, we have enough evidence to suggest that strategies adopted “from above” have been unable to engender transformations towards more just and liveable futures. Situating the paper within recent calls for a “post‐adaptation” turn in the field, I propose a generative critique of climate‐informed development through the lens of care as a place from where to begin thinking and practicing development differently. The aim of this critique is not to discard or discredit development practices as necessarily tainted or flawed but to make them accountable to a whole set of concerns and cares going into their stories of success or failures. Throughout the paper, I therefore speculatively ask the reader to think though the possibilities that may be opened when we stop treating climate‐informed development projects as neutral and undisputable “matters of fact,” engaging with them instead as necessary and non‐innocent “matters of care.” Thinking through a tryptic notion of “matters of care,” as at the same time a neglected doing necessary for the sustenance of life, an affective state, and an ethico‐politics, I look at examples from semi‐arid areas of India to give visibility to those practices, relations, and emotions of care that have been marginalised by mainstream development circles. Through this shift in perception, a deeper understanding of vulnerability as a state of shared fragility emerges, one that grounds an ethico‐politics of climate‐informed development to concrete circumstances and becomes the foundation upon which more inclusive practices can be built upon.
    • The relationship between target joints and direct resource use in severe haemophilia

      O’Hara, Jamie; Walsh, Shaun; Camp, Charlotte; Mazza, Giuseppe; Carroll, Liz; Hoxer, Christina; Wilkinson, Lars; University of Chester; HCD Economics, The Innovation Centre, Daresbury; University College London; The Haemophilia Society; Novo Nordisk A/S (SpringerOpen, 2018-01-16)
      Objectives Target joints are a common complication of severe haemophilia. While factor replacement therapy constitutes the majority of costs in haemophilia, the relationship between target joints and non drug-related direct costs (NDDCs) has not been studied. Methods Data on haemophilia patients without inhibitors was drawn from the ‘Cost of Haemophilia across Europe – a Socioeconomic Survey’ (CHESS) study, a cost assessment in severe haemophilia A and B across five European countries (France, Germany, Italy, Spain, and the United Kingdom) in which 139 haemophilia specialists provided demographic and clinical information for 1285 adult patients. NDDCs were calculated using publicly available cost data, including 12-month ambulatory and secondary care activity: haematologist and other specialist consultant consultations, medical tests and examinations, bleed-related hospital admissions, and payments to professional care providers. A generalized linear model was developed to investigate the relationship between NDDCs and target joints (areas of chronic synovitis), adjusted for patient covariates. Results Five hundred and thirteen patients (42% of the sample) had no diagnosed target joints; a total of 1376 target joints (range 1–10) were recorded in the remaining 714 patients. Mean adjusted NDDCs for persons with no target joints were EUR 3134 (standard error (SE) EUR 158); for persons with one or more target joints, mean adjusted NDDCs were EUR 3913 (SE EUR 157; average mean effect EUR 779; p < 0.001). Conclusions Our analysis suggests that the presence of one or more target joints has a significant impact on NDDCs for patients with severe haemophilia, ceteris paribus. Prevention and management of target joints should be an important consideration of managing haemophilia patients.
    • Relationships among unmet needs, depression, and anxiety in non–advanced cancer patients

      Ferrari, Martina; Ripamonti, Carla I.; Hulbert-Williams, Nicholas J.; Miccinesi, Guido (SAGE Publications, 2018-04-16)
      Introduction: In oncology settings, less attention is given to patients’ unmet needs and to existential and emotional distress compared to physical symptoms. We aimed to evaluate correlations between unmet needs and emotional distress (self-reported anxiety and depression) in a consecutive cohort of cancer patients. The influence of sociodemographic and clinical factors was also considered. Methods: A total of 300 patients with cancer recruited from an outpatient Supportive Care Unit of a Comprehensive Cancer Centre completed the Need Evaluation Questionnaire and the Edmonton Symptom Assessment System (ESAS). Unmet needs covered 5 distinct domains (informational, care/assistance, relational, psychoemotional, and material). Results: After removal of missing data, we analyzed data from 258 patients. Need for better information on future health concerns (43%), for better services from the hospital (42%), and to speak with individuals in the same condition (32%) were the most frequently reported as unmet. Based on the ESAS, 27.2% and 17.5% of patients, respectively, had a score of anxiety or depression &gt;3 and needed further examination for psychological distress. Female patients had significantly higher scores for anxiety ( p &lt; 0.001) and depression ( p = 0.008) compared to male patients. Unmet needs were significantly correlated with both anxiety ( rs = 0.283) and depression ( rs = 0.284). Previous referral to a psychologist was significantly associated with depression scores ( p = 0.015). Results were confirmed by multiple regression analysis. Conclusions: Screening for unmet needs while also considering sociodemographic and clinical factors allows early identification of cancer patients with emotional distress. Doing so will enable optimal management of psychological patient-reported outcomes in oncology settings.
    • Religion, Spirituality and Addiction Recovery: Introduction

      Dossett, Wendy; Metcalf-White, Liam (Equinox Publishing, 2020-02-13)
    • Reporting Microaggressions: Kinship Carers’ Complaints about Identity Slights

      Wilkes, Julie; orcid: 0000-0003-4768-3825; email: julie.wilkes@postgrad.manchester.ac.uk; Speer, Susan A. (SAGE Publications, 2020-10-28)
      The psychological concept of “microaggression” has refocused interest on what counts as prejudicial action. It redirects attention from standard socio-cognitive explanations of overt prejudice among social groups toward recipients’ perspectives of largely unwitting and subtle everyday racism. Microaggression studies define common implicit identity challenges faced by minority groups, including kinship carers. However, criticisms of the “microaggressions program” raise difficulties inherent in establishing prejudicial action from accounts of necessarily ambiguous actions, and contend that reliance on self-reporting inevitably lacks validity. This conversation analytic (CA) study offers a complementary approach: from videos of ten kinship carer support groups it shows how participants construct accountabilities for prejudicial actions in their retrospective reports of questions, challenges and suspicions in ways that build these actions as microaggressive. It addresses methodological shortcomings in microaggression studies, and extends CA research on accountability in offense construction, and on prejudicial social actions that are contested and difficult to analyze.
    • The ReSiT study (reducing sitting time): rationale and protocol for an exploratory pilot study of an intervention to reduce sitting time among office workers

      Gardner, Benjamin; Dewitt, Stephen; Smith, Lee; Buckley, John P.; Biddle, Stuart J. H.; Mansfield, Louise; King's College London; Anglia Ruskin University; University of Chester; University of Southern Queensland; Brunel University (BioMed Central, 2017-11-28)
      Background Desk-based workers engage in long periods of uninterrupted sitting time, which has been associated with morbidity and premature mortality. Previous workplace intervention trials have demonstrated the potential of providing sit-stand workstations, and of administering motivational behaviour change techniques, for reducing sitting time. Yet, few studies have combined these approaches or explored the acceptability of discrete sitting-reduction behaviour change strategies. This paper describes the rationale for a sitting-reduction intervention that combines sit-stand workstations with motivational techniques, and procedures for a pilot study to explore the acceptability of core intervention components among university office workers. Methods The intervention is based on a theory and evidence-based analysis of why office workers sit, and how best to reduce sitting time. It seeks to enhance motivation and capability, as well as identify opportunities, required to reduce sitting time. Thirty office workers will participate in the pilot study. They will complete an initial awareness-raising monitoring and feedback task and subsequently receive a sit-stand workstation for a 12-week period. They will also select from a ‘menu’ of behaviour change techniques tailored to self-declared barriers to sitting reduction, effectively co-producing and personally tailoring their intervention. Interviews at 1, 6, and 12 weeks post-intervention will explore intervention acceptability. Discussion To our knowledge, this will be the first study to explore direct feedback from office workers on the acceptability of discrete tailored sitting-reduction intervention components that they have received. Participants’ choice of and reflections on intervention techniques will aid identification of strategies suitable for inclusion in the next iteration of the intervention, which will be delivered in a self-administered format to minimise resource burden. Trial registration ISRCTN29395780 (registered 21 November 2016)
    • Restoring fertility in yeast hybrids: Breeding and quantitative genetics of beneficial traits.

      Naseeb, Samina; orcid: 0000-0003-3599-5813; Visinoni, Federico; orcid: 0000-0001-9840-7017; Hu, Yue; Hinks Roberts, Alex J; Maslowska, Agnieszka; Walsh, Thomas; Smart, Katherine A; Louis, Edward J; orcid: 0000-0003-1157-3608; Delneri, Daniela; orcid: 0000-0001-8070-411X (2021-09-21)
      Hybrids between species can harbor a combination of beneficial traits from each parent and may exhibit hybrid vigor, more readily adapting to new harsher environments. Interspecies hybrids are also sterile and therefore an evolutionary dead end unless fertility is restored, usually via auto-polyploidisation events. In the genus, hybrids are readily found in nature and in industrial settings, where they have adapted to severe fermentative conditions. Due to their hybrid sterility, the development of new commercial yeast strains has so far been primarily conducted via selection methods rather than via further breeding. In this study, we overcame infertility by creating tetraploid intermediates of interspecies hybrids to allow continuous multigenerational breeding. We incorporated nuclear and mitochondrial genetic diversity within each parental species, allowing for quantitative genetic analysis of traits exhibited by the hybrids and for nuclear-mitochondrial interactions to be assessed. Using pooled F12 generation segregants of different hybrids with extreme phenotype distributions, we identified quantitative trait loci (QTLs) for tolerance to high and low temperatures, high sugar concentration, high ethanol concentration, and acetic acid levels. We identified QTLs that are species specific, that are shared between species, as well as hybrid specific, in which the variants do not exhibit phenotypic differences in the original parental species. Moreover, we could distinguish between mitochondria-type-dependent and -independent traits. This study tackles the complexity of the genetic interactions and traits in hybrid species, bringing hybrids into the realm of full genetic analysis of diploid species, and paves the road for the biotechnological exploitation of yeast biodiversity. [Abstract copyright: Copyright © 2021 the Author(s). Published by PNAS.]
    • Reviews

      Waddell, Brodie; Hooke, Della; Hawkins, Harry; Bowen, James P.; Silvester, Bob; Frost, Robert; Donaldson, Christopher; Mitchell, Elaine; Watkinson, Martin; Martin, John (Informa UK Limited, 2019-10-17)
    • Right cardiac chambers echo‐bubble contrast in a patient with decompression sickness: A case report and a literature review

      Harfoush, Allam; orcid: 0000-0001-7317-4237; email: allamharf@gmail.com; Ramadan, Mohammad; Hamdallah, Hanady (2022-04-14)
      Abstract: The diagnosis of decompression sickness (DCS) is mostly based on clinical suspicion, and there is currently no available modality to fully confirm the diagnosis. However, the use of echocardiography in suspected DCS cases has become more common. In this case, transthoracic echocardiography (TTE) was used to detect microbubbles in the right cardiac chambers and monitor the patient after hyperbaric oxygen therapy (HBOT), suggesting the possible applicability of TTE in diagnosing and monitoring DCS patients. This report describes a 54‐year‐old Fisherman who was referred to the emergency department with dyspnea and mild confusion after a rapid ascent of a saturation dive at 50 m sea depth. After the initial evaluation, he was assessed using TTE to exclude the presence of structural heart disease, where it surprisingly showed spontaneous echo contrast inside the right cardiac chambers similar to agitated saline echo testing. The patient was then admitted for HBOT and follow‐up; rapid improvement was noticed after the first HBOT session and the TTE findings were fully resolved. TTE could be considered in the initial workup when DCS is suspected, and it might have a role in monitoring DCS patients if echocardiographic findings of bubble formation were documented in the pre‐hyperbaric therapy settings.
    • Right cardiac chambers echo‐bubble contrast in a patient with decompression sickness: A case report and a literature review

      Harfoush, Allam; orcid: 0000-0001-7317-4237; Ramadan, Mohammad; Hamdallah, Hanady (Wiley, 2022-04-14)
    • Risk factors for self-harm repetition in adolescents: A systematic review.

      Rahman, Farhan; Webb, Roger T; Wittkowski, Anja; email: anja.wittkowski@manchester.ac.uk (2021-05-29)
      Self-harm behavior can begin in early adolescence, with the highest rates of self-harm, between 1990 and 2000 in England, being among adolescents aged 16 to 24 years and there being considerable risk of fatal and non-fatal repetition. Previous systematic reviews have identified risk factors for self-harm in adolescents, but not for the repetition of this behavior. The aim of this review was to synthesise the psychological, psychosocial and sociodemographic risk factors for self-harm repetition in adolescents. By searching four databases, 27 studies were identified and included in the review. Several psychological (e.g., psychiatric morbidity, features of previous self-harm, psychological distress), psychosocial (e.g., alcohol misuse, poor family and peer relationships) and sociodemographic (e.g., age, gender and ethnicity) risk factors were identified for self-harm repetition in adolescents. Several risk factors across all categories for self-harm overlapped with that of self-harm repetition, such as depression, alcohol misuse and female gender. The clinical implications of these findings for practitioners were discussed. As was the case with prior reviews in this area, comparability between studies was limited and a meta-analysis was not possible due to considerable heterogeneity in outcome definitions, measures and methodologies. [Abstract copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.]
    • Risk of harm to others: subjectivity and meaning of risk in mental health practice

      Nathan, Rajan; Whyler, Jonathon; Wilson, Peter (Informa UK Limited, 2020-09-11)