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Sunscreen along with the Protective Principle.
sions, please email [email protected] Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a). METHODS AND RESULTS Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (-17%, P  less then  0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C). CONCLUSION Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a). © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Intravenous third-line anaesthetic agents are typically titrated in refractory status epilepticus to achieve either seizure suppression or burst suppression on continuous EEG. However, the optimum treatment paradigm is unknown and little data exist to guide the withdrawal of anaesthetics in refractory status epilepticus. Premature withdrawal of anaesthetics risks the recurrence of seizures, whereas the prolonged use of anaesthetics increases the risk of treatment-associated adverse effects. This study sought to measure the accuracy of features of EEG activity during anaesthetic weaning in refractory status epilepticus as predictors of successful weaning from intravenous anaesthetics. We prespecified a successful anaesthetic wean as the discontinuation of intravenous anaesthesia without developing recurrent status epilepticus, and a wean failure as either recurrent status epilepticus or the resumption of anaesthesia for the purpose of treating an EEG pattern concerning for incipient status epilepticus. We evalh an area under the curve of 83.3%. Distinct signatures in the spatial networks of functional connectivity emerge during successful anaesthetic liberation in status epilepticus; these findings are absent in patients with anaesthetic wean failure. Identifying features that emerge during successful anaesthetic weaning may allow faster and more successful anaesthetic liberation after refractory status epilepticus. © The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email [email protected] mitral valve repair with NeoChord implantation is effective and safe to replace ruptured chordae due to degenerative disease. Redo transapical neochordae implantation has never been reported in the literature. We present a case report of a 53-year-old man who underwent a reoperative neochord implantation for recurrent severe mitral regurgitation, resulting from degenerative disease progression with a new native chordal rupture. We report the midterm durability of reoperative Neochord repair. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.BACKGROUND Recent advances in the study and clinical applications of circulating tumor DNA (ctDNA) are limited by practical considerations of sample collection. Whole-genome sequencing (WGS) is increasingly used for analysis of ctDNA, identifying copy-number alterations and fragmentation patterns. We hypothesized that low-depth/shallow WGS (sWGS) data may be generated from minute amounts of cell-free DNA, and that fragment-size selection may remove contaminating genomic DNA from small blood volumes. Dried blood spots have practical advantages for sample collection, may facilitate serial sampling, and could support novel study designs in humans and animal models. METHODS We developed a protocol for the isolation and analysis of cell-free DNA from dried blood spots using filter paper cards and bead-based size selection. DNA extracted and size-selected from dried spots was analyzed using sWGS and polymerase chain reaction (PCR). RESULTS Analyzing a 50 μL dried blood spot from frozen whole blood of a patient with melanoma, we identified ctDNA based on the presence of tumor-specific somatic copy-number alterations, and found a fragment-size profile similar to that observed in plasma DNA. We found alterations in different chromosomes in blood spots from 2 patients with high-grade serous ovarian carcinoma. Extending this approach to serial dried blood spots from mouse xenograft models, we detect tumor-derived cell-free DNA and identified ctDNA from the originally grafted ascites. AZD7762 clinical trial CONCLUSION Our data suggest that ctDNA can be detected and monitored in dried blood spots from archived and fresh blood samples, enabling new approaches for sample collection and novel study/trial designs for both patients and in vivo models. © American Association for Clinical Chemistry 2020.Acquired hemophilia A (AHA) is due to autoantibodies against coagulation factor VIII (FVIII) and most often presents with unexpected bleeding. In contrast to congenital hemophilia, the patient's residual FVIII activity does not seem to correlate with the risk of bleeding as suggested from previous studies. Risk factors for bleeding have not been described. We used data from the prospective GTH-AH 01/2010 study to assess the risk of bleeding and the efficacy of hemostatic therapy. FVIII activity was measured at baseline and weekly thereafter. Bleeding events were assessed by treating physicians. A total of 289 bleeds was recorded in 102 patients. 141 new bleeds starting after day 1 were observed in 59% of the patients, with a mean rate of 0.13 bleeds per patient-week in weeks 1 to 12, or 0.27 bleeds per patient-week before achieving partial remission. Weekly measured FVIII activity was significantly associated with the bleeding rate, but only achieving FVIII ≥50% abolished the risk of bleeding. A good WHO performance status assessed at baseline (score 0 vs. higher) was associated with a lower bleeding rate. Hemostatic treatment was reported to be effective in 96% of bleeds. In conclusion, the risk of new bleeds after a first diagnosis of AHA remains high until partial remission is achieved, and weekly measured FVIII activity may help to assess the individual risk of bleeding. These results will help to define future strategies for prophylaxis of bleeding in AHA. Copyright © 2020 American Society of Hematology.STUDY QUESTION What is it like for women to be involuntarily childless in midlife? SUMMARY ANSWER Involuntarily childless women may be suffering from prolonged grief due to its ambiguous and intangible nature; however, they are also striving to find ways of dealing with their internal pain in order to live with their loss. WHAT IS KNOWN ALREADY Many studies examining issues around human reproduction have tended to place childlessness in the realm of medicalised infertility and report generalised mental issues, such as depression and psychological distress, existing amongst women undergoing fertility treatments. Few studies, however, have focused on the individual with regard to the experiential significance of involuntary childlessness and living beyond the phase of trying for a baby. STUDY DESIGN, SIZE, DURATION A phenomenologically oriented person-centred qualitative design was used. In-depth semi-structured interviews were conducted with 12 White British women, who identified themselves as involuntarily chiagnosed with prolonged grief disorder (PGD). The overall findings elucidate the need for clinicians, counsellors and health professionals to be aware of the possible association with PGD and promote long-term support and care in helping to maintain psychological well-being for people dealing with involuntary childlessness. Furthermore, this research points to an educational application for younger people by offering information beyond an explanation of infertility and fertility treatment, helping to understand the lived experience of involuntary childlessness. STUDY FUNDING/COMPETING INTEREST(S) No funding was obtained for this study. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER Not applicable. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail [email protected] develop and pilot a tool that assesses the infrastructure and policy workplace environment characteristics that may influence employee healthy eating and physical activity behaviours. A checklist was developed with reference to prior tools and piloted at eight worksites. Piloting of the tool demonstrated that it was generally feasible to use, took 1-2 hours to complete and appeared sensitive to differences between workplace environment characteristics. Refinement of the tool occurred after piloting. The final 21-item checklist contains sub-scores capturing policy, infrastructure, healthy eating and physical activity characteristics. This new checklist overcomes some limitations of pre-existing tools as it explicitly considers policy and is short, inexpensive and can be used by workplaces for self-assessment and by health promotion professionals in evaluation studies or as an intervention tool. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email [email protected] accreditation has been transferred from high-income countries (HICs) to many low- and middle-income countries (LMICs), supported by a variety of advocates and donor agencies. This review uses a policy transfer theoretical framework to present a structured analysis of the development of hospital accreditation in LMICs. The framework is used to identify how governments in LMICs adopted accreditation from other settings and what mechanisms facilitated and hindered the transfer of accreditation. The review examines the interaction between national and international actors, and how international organizations influenced accreditation policy transfer. Relevant literature was found by searching databases and selected websites; 78 articles were included in the analysis process. The review concludes that accreditation is increasingly used as a tool to improve the quality of healthcare in LMICs. Many countries have established national hospital accreditation programmes and adapted them to fit their national contexts.
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