Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?

Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future.info:eu-repo/semantics/publishedVersio

Factors that influence the uptake of routine antenatal services by pregnant women: a qualitative evidence synthesis

A B S T R A C T This is a protocol for a Cochrane Review (Qualitative). The objectives are as follows: To identify, appraise, and synthesise qualitative studies exploring: • women’s views and experiences of antenatal care; and • factors influencing the uptake of antenatal care arising from women’s accounts

Popliteal lymph node dissection for metastatic squamous cell carcinoma: a case report of an uncommon procedure for an uncommon presentation

Lymph node metastasis from cutaneous squamous cell carcinoma is uncommon. The popliteal fossa is rarely involved with metastasis. Popliteal lymph node dissection is uncommonly performed and not frequently discussed in the literature. We present a case of squamous cell carcinoma of the heel with popliteal and inguinal metastasis. This is followed by a description of the relevant anatomy of the popliteal fossa and the technique of popliteal lymphadenectomy

Moral Behavior

Prosocial and antisocial behaviors take place in sport and correspond to proactive and inhibitive morality. These behaviors could have important consequences not only for the recipient's physical and psychological well being, but also for the quality of the overall sport experience. Thus, understanding the factors that lead to, or inhibit, these behaviors is important. Motivational variables stemming from achievement goal theory and self-determination theory have been associated with both prosocial and antisocial behaviors in sport, highlighting the important role of motivation on moral behavior. Moral disengagement, a strong positive predictor of antisocial behavior, could explain the effects of motivational variables on this behavior. Moral variables are also highly influential with both moral identity and empathy inhibiting antisocial behavior; anticipated guilt has been identified as a mediator in this process, underlining the significance of emotion on moral behavior. Finally, bracketed morality exists in sport, and may be a manifestation of the intergroup bias phenomenon

Association of MUTYH and colorectal cancer

Mutations in the MUTYH gene have been reported to be associated with increased risk of developing colorectal cancer. In this study, we confirmed this association using original data on 928 colorectal cancer cases and 845 healthy controls from Scotland. We then conducted a meta-analysis from published data on the association between mutations at MUTYH and colorectal cancer risk. We show for the first time a small but significant mono-allelic effect with a genotype relative risk (GRR) of 1.27 (95% confidence interval (CI): 1.01–1.61), and confirm and give a more precise estimate of the strong bi-allelic effect with an estimated GRR of 117 (95% CI: 74–184). This study underscores the need for large sample sizes in order to identify small gene effects when the disease allele frequency is low

Alliance or acquisition? A mechanisms‐based, policy‐capturing analysis

Research summary: While alliance researchers view prior partner‐specific alliance experience as influencing firms' subsequent alliance or acquisition decisions, empirical evidence on the alliance versus acquisition decision is surprisingly mixed. We offer a reconciliation by proposing and testing an analytical framework that recognizes prior partner‐specific experiences as heterogeneous along three fundamental dimensions: partner‐specific trust, routines, and value certainty. This allows us to use a policy‐capturing methodology to rigorously operationalize and test our mechanism‐level predictions. We find that all three mechanisms can increase the likelihood of a subsequent alliance or acquisition, and in terms of the comparative choice between alliances versus acquisitions, partner‐specific trust pulls towards alliances, and value certainty pulls towards acquisitions. We conclude with a discussion of the theoretical and empirical implications of our approach and method. Managerial summary: This study focuses on an important corporate decision: When a firm has had an alliance with another firm, how would that experience affect the likelihood of a future alliance or acquisition with that same firm? We first suggest that it will depend on three factors: the level of trust that existed in that prior alliance, the extent to which specific work routines were developed, and the degree to which the firm was able to confidently assess the value of the partner firm's resources. We then find that trust is a particularly strong predictor of future alliances, while confidence regarding value more strongly predicts future acquisitions. In this way, we demonstrate more precisely how past corporate choices can affect (consciously or unconsciously) future ones

Open a GLAM lab

Defining a GLAM Lab: A Galleries, Libraries, Archives and Museums (GLAM) Lab is a place for experimenting with digital collections and data. It is where researchers, artists, entrepreneurs, educators and the interested public can collaborate with an engaged group of partners to create new collections, tools, and services that will help transform the future ways in which knowledge and culture are disseminated. The exchanges and experimentation in a Lab are open, iterative and shared widely. This book describes why and how to open a GLAM Lab and encourages participation in a movement that can transform organisations and the communities they partner with. Building a GLAM Lab: Building a GLAM Lab involves defining its core values to guide future work, fostering a culture that is open, transparent, generous, collaborative, creative, inclusive, bold, ethical, accessible and encourages a mindset of exploration. The Lab should be grounded in user-centred and participatory design processes and its staff should be able to clearly communicate what the Lab is about. It's important to think big but start small and establish quick wins to get up and running. GLAM Lab teams: There are recommendations for the qualities and skills to look for in Labs teams, how to go about finding allies within and outside the institution, and ideas on how to create a nurturing environment for teams to thrive in. Labs teams have no optimal size or composition, and its team members can come from all walks of life. Teams need a healthy culture to ensure a well-functioning Lab which might be augmented intermittently by fellows, interns or researchers-inresidence. For a Lab to have lasting impact it must be integrated into the parent organisation and have the support of staff at all levels. User communities: GLAM Labs will need to engage and connect with potential users and partners. This means rethinking these relationships to help establish clear and targeted messages for specific communities. In turn, this enables Labs to adjust their tools, services and collections to establish deeper partnerships based on co-creation, and open and equal dialogue. Rethinking collections and Data: The book discusses the digital collections which are an integral part of Labs. It provides insights on how to share the collections as data, and how to identify, assess, describe, access, and reuse the collections. In addition, there is information about messy and curated data, digitisation, metadata, rights and preservation. Transformation: Experimentation is the critical core of the Lab's process. Insights about how to transform tools into operational services are demonstrated. It shows that experimentation can prepare the organisational culture and services for transformation. There is an examination of funding and the advantages and disadvantages of various models through discussion of the different mechanisms and options that an organisation can apply to Lab set-ups. Funding and Sustainability: We share insights on how to plan for a Lab's sustainability as well as a step-by-step guide for when an organisation is retiring or decommissioning a Lab. Labs have a pivotal role in the transformation of GLAMs and the book highlights the critical importance of Labs in changing the future of digital cultural heritage.Funded by UCL Qatar (Mmember of Qatar Foundation) and Qatar University Library. There has also been support from the British Library Labs, and the Library of Congress Labs

Global and regional brain metabolic scaling and its functional consequences

Background: Information processing in the brain requires large amounts of metabolic energy, the spatial distribution of which is highly heterogeneous reflecting complex activity patterns in the mammalian brain. Results: Here, it is found based on empirical data that, despite this heterogeneity, the volume-specific cerebral glucose metabolic rate of many different brain structures scales with brain volume with almost the same exponent around -0.15. The exception is white matter, the metabolism of which seems to scale with a standard specific exponent -1/4. The scaling exponents for the total oxygen and glucose consumptions in the brain in relation to its volume are identical and equal to $0.86\pm 0.03$, which is significantly larger than the exponents 3/4 and 2/3 suggested for whole body basal metabolism on body mass. Conclusions: These findings show explicitly that in mammals (i) volume-specific scaling exponents of the cerebral energy expenditure in different brain parts are approximately constant (except brain stem structures), and (ii) the total cerebral metabolic exponent against brain volume is greater than the much-cited Kleiber's 3/4 exponent. The neurophysiological factors that might account for the regional uniformity of the exponents and for the excessive scaling of the total brain metabolism are discussed, along with the relationship between brain metabolic scaling and computation.Comment: Brain metabolism scales with its mass well above 3/4 exponen

New functionalities of Maillard reaction products as emulsifiers and encapsulating agents, and the processing parameters: a brief review

Non-enzymatic browning has been a wide and interesting research area in the food industry, ranging from the complexity of the reaction to its applications in the food industry as well as its ever-debatable health effects. This review provides a new perspective to the Maillard reaction apart from its ubiquitous function in enhancing food flavour, taste and appearance. It focuses on the recent application of Maillard reaction products as an inexpensive and excellent source of emulsifiers as well as superior encapsulating matrices for the entrapment of bioactive compounds. Additionally, it will also discuss the latest approaches employed to perform the Maillard reaction as well as several important reaction parameters that need to be taken into consideration when conducting the Maillard reaction

A mutation of EPT1 (SELENOI) underlies a new disorder of Kennedy pathway phospholipid biosynthesis.

Mutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes. We determined that the mutation defined dramatically reduces the enzymatic activity of EPT1, thereby hindering the final step in phosphatidylethanolamine synthesis. Additionally, due to central nervous system inaccessibility we undertook quantification of phosphatidylethanolamine levels and species in patient and control blood samples as an indication of liver phosphatidylethanolamine biosynthesis. Although this revealed alteration to levels of specific phosphatidylethanolamine fatty acyl species in patients, overall phosphatidylethanolamine levels were broadly unaffected indicating that in blood EPT1 inactivity may be compensated for, in part, via alternate biochemical pathways. These studies define the first human disorder arising due to defective CDP-ethanolamine biosynthesis and provide new insight into the role of Kennedy pathway components in human neurological function