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Pre-eclampsia with severe features (severe PreE) is associated with heart dysfunction, yet the impact beyond pregnancy, including its association with cardiomyopathic genetic polymorphisms, remains poorly understood. We aimed to characterize the temporal impact of severe PreE on heart function through the 4th trimester in women with and without deleterious cardiomyopathic genetic variants. Pregnant women were enrolled to undergo transthoracic echocardiography (TTE) in late pregnancy and 3 months postpartum. In women with severe PreE a targeted approach to identify pathogenic cardiomyopathic genetic polymorphisms was undertaken, and heart function was compared in carriers and noncarriers. Pregnant women (32 ± 4 years old, severe PreE = 14, control = 8) were enrolled between 2019 - 2021. Women with severe PreE displayed attenuated myocardial relaxation (mitral e' = 11.0 ± 2.2 vs 13.2 ± 2.3 cm/sec, P <.05) in late pregnancy, and on in-silico analysis, deleterious cardiomyopathic variants were found in 58%. At 103 ± 33 days postpartum, control women showed stability in myocardial relaxation (Mitral e' Entry: 13.2 ± 2.3 vs Postpartum: 13.9 ± 1.7cm/sec, P =.464), and genetic negative severe PreE women (G−) demonstrated recovery of diastolic function to control level (Mitral e' Entry: 11.0 ± 3.0 vs Postpartum 13.7 ± 2.8cm/sec, P <.001), unlike their genetic positive (G+) counterparts (Mitral e' Entry: 10.5 ± 1.7 vs Postpartum 10.8 ± 2.4cm/sec, P =.853). Postpartum recovery of heart function after severe PreE is attenuated in women with deleterious cardiomyopathic genetic polymorphisms. [Display omitted] [ABSTRACT FROM AUTHOR]

The structural changes of airway smooth muscle (ASM) that characterize airway remodeling (AR) are crucial to the pathogenesis of asthma. During AR, ASM cells dedifferentiate from a quiescent to a proliferative, migratory, and secretory phenotype. Calcium (Ca2+) is a ubiquitous second messenger that regulates many cellular processes, including proliferation, migration, contraction, and metabolism. Furthermore, mitochondria have emerged as major Ca2+ signaling organelles that buffer Ca2+ through uptake by the mitochondrial Ca2+ uniporter and extrude it through the Na+/Ca2+ exchanger (NCLX/Slc8b1). Here, we show using mitochondrial Ca2+-sensitive dyes that NCLX only partially contributes to mitochondrial Ca2+ extrusion in ASM cells. Yet, NCLX is necessary for ASM cell proliferation and migration. Through cellular imaging, RNA-Seq, and biochemical assays, we demonstrate that NCLX regulates these processes by preventing mitochondrial Ca2+ overload and supporting store-operated Ca2+ entry, activation of Ca2+/calmodulin-dependent kinase II, and transcriptional and metabolic reprogramming. Using small animal respiratory mechanic measurements and immunohistochemistry, we show that smooth muscle-specific NCLX KO mice are protected against AR, fibrosis, and hyperresponsiveness in an experimental model of asthma. Our findings support NCLX as a potential therapeutic target in the treatment of asthma. [ABSTRACT FROM AUTHOR]

The role of ablation of astroglial cells on the pathogenesis of jejuno-ileitis was investigated. The ablation of astroglial cells was targeted genetically and transgenic mice that express herpes simplex virus thymidine kinase (HSV-TK) were generated. Results show that the pattern and regulation of HSV-TK expression is the same as that of endogenous glial fibrillary acidic protein promoter. It was also found that a fulminating and fatal jejuno-ileitis occurs following ablation of astroglial cells.

The role of special interest groups in the long-delayed US and EC negotiations of agricultural poilcies is examined through an estimated political payoff function. A world trade model coupled with game theory is developed to search for mutually acceptable agreements between the two parties. Simulation results show that major trade liberalization will not be attained without some form of decoupled payments and that without decoupled payments, any politically acceptable liberalization may be miniscule.

• A new therapeutic tool for use in different autoimmune diseases. • ET-traps are non-toxic. • The ET-traps could provide a novel treatment option for many areas of unmet need. Research shows that endothelin (ET)-traps are a potential therapy for diabetes. Given that type 1 diabetes mellitus (T1DM) is an autoimmune disorder, ET-traps could also have an efficacious, therapeutic effect on other autoimmune diseases associated with pathologically elevated ET-1. Here, we describe those different autoimmune diseases that might benefit from a tool such as ET-traps, which potently sequester these elevated levels of ET-1. We also discuss the current use of ET receptor (ETR) antagonists and the associated adverse effects, and how ET-traps are associated with no toxicity and potentially offer a superior alternative. ET-traps could be used against different autoimmune diseases and, therefore, are a novel therapeutic tool for such conditions. [ABSTRACT FROM AUTHOR]

Sociocultural discourse analysis is a methodology for studying the use of language for collective thinking. It was specifically designed for studying the talk of children working together in a group in a classroom, but it has also been used for studying talk amongst adults. In this article we discuss its use, in an adapted form, for analysing the professional discussions of examiners who are involved in making assessments of the essays of school students. We explain how and why the methodology was chosen and adapted, and show what its use reveals about collective intellectual activity in this particular context. We conclude with some comments about the value of this methodological approach for examining professional discourse more widely. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Cellular remodeling is a common theme in cardiorespiratory diseases. • ORAI channels are calcium (Ca2+) selective channels and have emerged as significant regulators of cellular remodeling during disease. • This review details how dysregulation in ORAI channel expression and activation contributes to cellular remodeling in cardiorespiratory diseases. • ORAI channels may be potential pharmaceutical targets in cardiorespiratory diseases. Abstract Cardiorespiratory disease, which includes systemic arterial hypertension, restenosis, atherosclerosis, pulmonary arterial hypertension, asthma, and chronic obstructive pulmonary disease (COPD) are highly prevalent and devastating diseases with limited therapeutic modalities. A common pathophysiological theme to these diseases is cellular remodeling, which is contributed by changes in expression and activation of ion channels critical for either excitability or growth. Calcium (Ca2+) signaling and specifically ORAI Ca2+ channels have emerged as significant regulators of smooth muscle, endothelial, epithelial, platelet, and immune cell remodeling. This review details the dysregulation of ORAI in cardiorespiratory diseases, and how this dysregulation of ORAI contributes to cellular remodeling. [ABSTRACT FROM AUTHOR]

The author discusses the challenges in reproductive medicine with poor-quality oocytes compounded by the falling ovarian reserve towards extinction as the menopause approaches. Topics discussed include importance of oocyte cryopreservation for fertility preservation, transfer of cytoplasm from donor oocytes to improve human oocyte quality, and factors of cytosolic deficiency.

Abstract: The transmission of wave energy passing an offshore wind farm is studied. Three effects that can change the wave field are analysed, which is the A) energy dissipation due to drag resistance, B) wave reflection/diffraction from structures, and C) the effect of a modified wind field inside and on the lee side of the wind farm. The drag dissipation, A), is quantified by a quadratic resistance law. The effect of B) is parameterised based on 1st order potential theory. A method to find the amount of reflected and transmitted wave energy is developed based on the panel method WAMIT™ and a radiation condition at infinity. From airborne and Satellite SAR (Synthetic Aperture Radar) a model has been derived for the change of the water surface friction C) inside and on the lee side of the offshore wind farm. The effects have been implemented in a spectral wind wave model, MIKE21 SW, and a parametric study to compare the 3 different processes has been carried out. The method to study reflection/diffraction can be used for any type of offshore structure, vessel or a number of structures, as long as the assumptions for the use of potential wave theory are valid, and the effect of the modified wind field on the water surface friction is known. [Copyright &y& Elsevier]

The article discusses whether mitochondria replacement therapy is giving rise to a tri-parentally derived child. The British Human Fertilisation and Embryology Authority (HFEA) reported its advice to the British government on mitochondrial replacement therapy following a public engagement consultation and expert advice on the safety and efficacy of the treatment. A commentary by F. Baylis on the health consequences of uncorrected mitochondrial disease for the offspring is discussed.

The origins of evidence-based medicine as understood today are traceable to 1972 and the publication of Archie Cochrane's book Effectiveness and Efficiency: Random Reflections on Health Services. This book attempted to bridge the divide between scientific medicine and clinical judgment that had developed since the mid-l9th century. Its genesis was stimulated by Cochrane's experiences as a prisoner-of-war medical officer and of the demands placed after the 1939-1945 war on the UK National Health Service. In the 1960s, reproductive medicine was considered by the UK Medical Research Council to be relatively 'unscientific' in its approach to care delivery and was described as such by Cochrane in the 1970s. Evidence is presented here that reproductive medicine responded, becoming by 1989 a pioneering clinical discipline in the application of evidence to practice. This was achieved largely through the efforts of lain Chalmers, who was a key player in the development of the systematic review and in the foundation of the Cochrane collection. [ABSTRACT FROM AUTHOR]

Summary: Background: Exhaled nitric oxide provides a convenient, non-invasive insight into airway inflammation. However it is suppressed by current smoking, reducing its potential as an endpoint in studies of smokers with asthma, a group with increased symptoms and poor clinical responses to corticosteroids. We examined extended nitric oxide analysis as some derived variables are thought to be unaffected. Therefore this approach could reveal hidden inflammation and enable its use as an exploratory endpoint in this group. Methods: Smokers (n = 22) and never smokers (n = 21) with asthma performed exhaled nitric oxide measurements and spirometry before and after two weeks of oral dexamethasone (6 mg/1.74 m2/day). Linear and non-linear nitric oxide analysis was performed to derive estimates for alveolar nitric oxide (Calv) and nitric oxide flux (J′aw) for each subject. Results: FENO50 was significantly lower in smokers with asthma and did not change significantly in response to dexamethasone. Calv derived by linear modelling was lower in smokers with asthma and did not change significantly in response in either group. J′aw was substantially lower in smokers with asthma (smokers (median (IQR)); 573 pl/s (217, 734), non-smoker; 1535 pl/s (785, 3496), p = 0.001) and was reduced in both groups following dexamethasone (non-smokers change (mean (95% CI)); −743.3 pl/s (−1710, −163), p = 0.005, smokers; −293 pl/s (−572, −60), p = 0.016). Correction for axial flow did not substantially change the derived results. Conclusions: Bronchial NO flux appears to be sensitive to oral dexamethasone and may provide a useful exploratory endpoint for the analysis of novel anti-inflammatory therapies in smokers with asthma. [ABSTRACT FROM AUTHOR]

Summary: The use of blended learning to develop the clinical knowledge and skills of healthcare professionals is increasing. This paper reports the qualitative findings from an evaluation of a blended learning course designed to equip registered nurses with the knowledge and skills required to practice competently in cardiac nursing. The aims of the study were to explore whether a cardiac care course could be successfully delivered mainly online and it had any impact on the students'' clinical practice. The sample consisted of course members and their mentors. Data were obtained through focus groups and interviews and analysed using thematic analysis. All students felt they had benefited from undertaking the course. Mentors identified higher levels of confidence and greater depth of knowledge and skills amongst their students. Areas identified for further development by both groups were firstly, the preparation of mentors for their role in supporting the students undertaking an online course and secondly, the expected level of competence that students needed to display in practice. This study indicates online learning is useful in enhancing student competence but may be wrongly seen as requiring less time commitment for both course members and mentors when compared to taught courses. [Copyright &y& Elsevier]

Summary: Background: Little is known about the characteristics of patients who were admitted to the coronary care unit (CCU) in the 1990s with non-ST elevation acute coronary syndromes (ACS) compared with those admitted to medical and cardiology wards in hospitals in the United Kingdom (UK). Aim: To understand if there were systematic differences in the characteristics of patients who were admitted to UK critical care units (CCU), intermediate care environments (cardiology wards) or generalist wards (acute medical ward) in an observational study carried out in the 1990s. Methods: This paper is based on a secondary analysis of PRAIS (UK), a prospective, observational, multi-centred study which recruited 1038 patients with non-ST elevation ACS. This analysis compares the characteristics of 860 of these patients dependent on whether they were cared for in a coronary care unit, acute medical ward or cardiology ward. Results: The results showed that patients admitted to CCU were more likely to be younger, male, have a history of diabetes or have ST depression on their ECG. There was very little difference in other risk factors or prior concomitant therapy. Interestingly there were no systematic differences in treatments or outcomes other than would be expected by chance, although there were trends to higher rates of MI and heart failure in the CCU group. Conclusion: Our analysis shows that the main drivers of admission to CCU in the 1990s were ST depression and MI—both indicators of high risk, but older age and female gender seemed to decrease the likelihood of admission to CCU. Criteria for admission to specific specialist and non-specialist care environments should be standardised and the use of risk scores could be an important way forward. [Copyright &y& Elsevier]

Summary: Recently we have witnessed several significant changes to the nursing curriculum in the United Kingdom (UK). This review forms part of a larger study evaluating the ‘fitness for practice’ elements of the nursing curriculum in Scotland. Systematic review methods were used including the following databases: CINAHL and BNI. Twenty six papers were retrieved and 14 remained after applying the review criteria, the main rationale being the empirical focus. It appears that there is a paucity of research in this area in the UK and papers dealt exclusively with either content, process or outcome evaluation of the nursing curriculum. National, well funded, multi-centre studies tended to be more rigorous. Results, where they were positive about curricular changes, tended to be limited. There is clearly a need for rigorous research into curriculum evaluation, both at the micro and macro level, which investigates content, process and outcome. Without such research, curriculum change will be uninformed. [Copyright &y& Elsevier]

Summary: In this paper we discuss the issues of caring and culture in practice settings and how they affect student nurses in their endeavours to learn how to be a ‘real nurse’. Drawing upon differing conceptions of ‘caring’ we discuss the notion as a pivotal factor in becoming a nurse. We examine the degree to which boundaries are changing, not least those in which students seem currently to define the bedrock of physical and emotional care as belonging to health care support workers whom they will merely supervise. Complicating this picture are developments in medical and nursing boundaries which may, or may not help to ‘professionalise’ nursing. We conclude by arguing that complex cultural norms and the negotiated order of health care need to be properly recognised by curriculum developers if, within contemporary higher education nurses are to be fit for purpose and practice. [Copyright &y& Elsevier]

Summary: This article presents a discussion of key issues for the education of nurses, midwives and health visitors following the completion of a Department of Health funded project, managed by the General Social Care Council and conducted jointly by two research centres; Salford Centre for Social Work Research and Salford Centre for Nursing, Midwifery and Collaborative Research. The work was initiated in response to Lord Laming’s report on the circumstances leading to the death of Victoria Climbié. The project was conducted in relation to specified professions and occupational groups: doctors; health visitors; midwives; nurses; police; teachers, and social workers. It was undertaken in two stages. The first stage mapped existing material about standards in relation to education and training for interagency working. The second stage engaged in an extensive consultation exercise through which a model and a set of proposed standards for interagency education and training for interagency work were developed. The former is detailed fully in this report, while nine examples of standards are presented. The project final report was presented seven months after commencement. [Copyright &y& Elsevier]

Summary: All issues of Nurse Education Today between January 1996 and July 2001 were examined manually and categorized as ‘research’ or other forms of scholarship. A total of 356 articles were reviewed and 193 of these were considered to be some form of research. The prevalence of well known methods of data collection was noted and broad trends identified. Questionnaires, reflective diaries, Delphi surveys, focus groups and individual interviews formed the backbone of methods used in educational research. There was a marked absence of experimental work. Proportionally more UK based papers avoided inferential analysis than those from overseas. We show that ‘research’ in Nurse Education Today has become rather narrow. It rarely incorporates ‘user’ (client/patient) perspectives, and rarely (especially in the UK) uses more than one site for study. More papers which undertake comparison of nurse education between countries, which employ samples from more than one country, and which address the impact of findings from an international perspective should be sought in order to enhance this aspect of the diversity of the journal. [Copyright &y& Elsevier]

Summary: In this literature review, we examine to what extent patient safety is addressed within medical and nursing curricula. Patient safety is the foundation of healthcare practice and education both in the UK and internationally. Recent research and policy initiatives have highlighted this issue. The paper highlights the significance of this topic as an aspect of study in its own right by examining not only the fiscal but also the human costs such events invite. In the United Kingdom patient safety issues feature prominently in the (Department of Health, 2000a. An organisation with a memory. The report of an expert group on learning from adverse events. The Stationery Office, London, Department of Health, 2000b. Handling complaints: monitoring the NHS complaints procedures (England, Financial year 1998–99). The Stationery Office, London.) policy documentation but this is not reflected within the formal curricula guidelines issued by the NMC and GMC. Yet if healthcare educational curricula were to recognise the value of learning from errors, such events could become part of a wider educational resource enabling both students and facilitators to prevent threats to patient safety. For this reason, the paper attempts to articulate why patient safety should be afforded greater prominence within medical and nursing curricula. We argue that learning how to manage errors effectively would enable trainee practitioners to improve patient care, reduce the burden on an overstretched health care system and engage in dynamic as opposed to defensive practice. [Copyright &y& Elsevier]

The increasing consumption of seafood products raises concerns over their sustainability and the conservation of marine resources. Seafood traceability, enabled by a regulated labelling system, is important to prevent overexploitation of these resources. The regulations (EU) No.1169/2011 and (EU) No 1379/2013 are the European legislative tools that specify the mandatory information that must be present on seafood labels. The present study analysed the labels of seafood products sold in different European countries in order to verify the presence of mandatory information required by EU regulations currently in place. The results show that there is a difference in compliance among groups of products and among countries. The country with the lowest level of compliance was The United Kingdom (still part of EU when the study was carried out), with an overall compliance of 63.7%. The country with the highest level of compliance was Portugal (87.2%). Across all the countries analysed, supermarkets were more compliant than fishmonger's shops and Processed Prepacked products were more conformed best to the EU labelling legislation when compared to Unprocessed Non-Prepacked products. Differences among different areas of the same country were also observed. Fishing gear, scientific name, fishing/production method and date of freezing were the types of information most frequently missing on the labels examined. The results of this study pose the bases for further actions, that can be taken by relevant institutions, to improve compliance throughout the supply chain. [ABSTRACT FROM AUTHOR]

Focuses on a study which examined the psychological impact which partners of women who had miscarriages encountered in relation to these experiences. Methodology used to conduct the study; Indepth look at the effect which miscarriages have on women; Results of the study.

The authors comment on an article on the possible impact of human mitochondrial replacement on global policy concerning germline gene modification. They argue against a proposal on Great Britain's wider responsibility in treating mitochondrial genetic diseases. They examine the feasibility of nuclear gene editing and some compelling clinical reasons for the use of nuclear gene editing.

The authors comment on the experience of a woman in Great Britain named Jane of infertility treatment and her suggestions to help empower men and women to take full control over their reproductive lives. The author relate the probable cause of the shame felt by Jane in her failure to conceive and the misplaced faith of Jane in her doctors in fertility clinics. They highlight the problems with Jane's call to improve school sex education and stress fertility decline as the age of women advances.

• ORAI channel isoforms are distinctly affected by pH and various pharmacological inhibitors and activators. • Synta66 inhibits ORAI1 and potentiates ORAI2 whereas IA65 potentiates ORAI1 and inhibits ORAI2. • ORAI heteromerization through concatenated constructs shapes the pharmacological profiles of CRAC channels. • Distinct ORAI isoform pharmacology would help determine the contribution of each isoform to CRAC channels in primary cells. The ubiquitous Ca2+ release-activated Ca2+ (CRAC) channel is crucial to many physiological functions. Both gain and loss of CRAC function is linked to disease. While ORAI1 is a crucial subunit of CRAC channels, recent evidence suggests that ORAI2 and ORAI3 heteromerize with ORAI1 to form native CRAC channels. Furthermore, ORAI2 and ORAI3 can form CRAC channels independently of ORAI1, suggesting diverse native CRAC stoichiometries. Yet, most available CRAC modifiers are presumed to target ORAI1 with little knowledge of their effects on ORAI2/3 or heteromers of ORAIs. Here, we used ORAI1/2/3 triple-null cells to express individual ORAI1, ORAI2, ORAI3 or ORAI1/2/3 concatemers. We reveal that GSK-7975A and BTP2 essentially abrogate ORAI1 and ORAI2 activity while causing only a partial inhibition of ORAI3. Interestingly, Synta66 abrogated ORAI1 channel function, while potentiating ORAI2 with no effect on ORAI3. CRAC channel activities mediated by concatenated ORAI1-1, ORAI1-2 and ORAI1-3 dimers were inhibited by Synta66, while ORAI2-3 dimers were unaffected. The CRAC enhancer IA65 significantly potentiated ORAI1 and ORAI1-1 activity with marginal effects on other ORAIs. Further, we characterized the profiles of individual ORAI isoforms in the presence of Gd3+ (5μM), 2-APB (5 μM and 50 μM), as well as changes in intracellular and extracellular pH. Our data reveal unique pharmacological features of ORAI isoforms expressed in an ORAI-null background and provide new insights into ORAI isoform selectivity of widely used CRAC pharmacological compounds. [ABSTRACT FROM AUTHOR]

Abstract: Special care of superficial lesions surrounding critical structures, such as an eye, may require tight margins. When this is the case, small megavoltage electron treatment fields and nonstandard treatment distances become necessary. When the field size is found to be less than the practical range of the electron beam, dosimetric measurements should be performed. This research includes data proving that very small electron fields can be employed for treatment with appropriate beam flatness and penumbra. This is accomplished by first coning down the incident beam to a small field size, then secondly by adding a single lead sheet to the patient’s skin surface. The aperture of the sheet is required to be greater than 2 × 2 cm2 in size, and must be cut properly to adequately confine the treatment area. [Copyright &y& Elsevier]

Lung cancer is a leading cause of cancer death and in suitable cases the best chance of cure is offered by surgery. Lung resection is associated with significant postoperative cardiorespiratory morbidity, with dyspnea and reduced functional capacity as dominant features. These changes are poorly associated with deterioration in pulmonary function and a potential role of right ventricular (RV) dysfunction has been hypothesized. Cardiovascular magnetic resonance imaging is a reference method for noninvasive assessment of RV function and has not previously been applied to this population. We used cardiovascular magnetic resonance imaging to assess the RV response to lung resection. Cardiovascular magnetic resonance imaging with volume and flow analysis was performed on 27 patients preoperatively, on postoperative day 2 and at 2 months. Left ventricular ejection fraction and RV ejection fraction, the ratio of stroke volume to end systolic volume, pulmonary artery acceleration time, and distensibility of main and branch pulmonary arteries were studied. Mean ± standard deviation RV ejection fraction deteriorated from 50.5% ± 6.9% preoperatively to 45.6% ± 4.5% on postoperative day 2 and remained depressed at 44.9% ± 7.7% by 2 months (P =.003). The ratio of stroke volume to end systolic volume deteriorated from median 1.0 (quartile 1, quartile 3: 0.9, 1.2) preoperatively to median 0.8 (quartile 1, quartile 3: 0.7, 1.0) on postoperative day 2 (P =.011). On postoperative day 2 there was a decrease in pulmonary artery acceleration time and operative pulmonary artery distensibility (P <.030 for both). There were no changes in left ventricular ejection fraction during the study period (P =.621). These findings suggest RV dysfunction occurs following lung resection and persists 2 months after surgery. The deterioration in the ratio of stroke volume to end systolic volume suggests a mismatch between afterload and contractility. There is an increase in indices of pulsatile afterload resulting from the operative pulmonary artery. [ABSTRACT FROM AUTHOR]

The article reflects on research related to outcomes of experimental treatments that involves ooplasmic transfers between 1996 and 2001 at Saint Barnabas Medical Centre in Livingston, New Jersey. It discusses adverse outcomes of a pregnancy that involved transfer of embryos generated by the technique of pronuclear transfer. It also mentions that the U.S. Food and Drug Administration (FDA) banned a research on two fetuses having mitochondria from two sources because of genetic abnormalities.