References 1. Conalogue DM, Kinn S, Mulligan J-A, McNeil M. International consultation on long-term global health research priorities, research capacity and research uptake in developing countries. Health Res Policy Syst. 2017;15(1):24-24.2. Poot CC, van der Kleij RM, Brakema EA, et al. From research to evidence-informed decision making: a systematic approach. Journal of Public Health. 2018;40(suppl_1):i3-i12.3. Brownson RC, Fielding JE, Green LW. Building capacity for evidence-based public health: reconciling the pulls of practice and the push of research. Annual review of public health. 2018;39:27-53.4. Milner M, Estabrooks CA, Myrick F. Research utilisation and clinical nurse educators: a systematic review. Journal of Evaluation in Clinical Practice. 2006;12(6):639-655.5. El-Jardali F, Lavis J, Moat K, Pantoja T, Ataya N. Capturing lessons learned from evidence-to-policy initiatives through structured reflection. Health Res Policy Syst. 2014;12:2-2.6. Langlois EV, Becerril Montekio V, Young T, Song K, Alcalde-Rabanal J, Tran N. Enhancing evidence informed policymaking in complex health systems: lessons from multi-site collaborative approaches. Health Res Policy Syst. 2016;14:20-20.7. Barratt H, Shaw J, Simpson L, Bhatia S, Fulop N. Health services research: building capacity to meet the needs of the health care system.J Health Serv Res Policy. 2017;22(4):243-249.8. Straus SE, Tetroe JM, Graham ID. Knowledge translation is the use of knowledge in health care decision making. Journal of Clinical Epidemiology. 2011;64(1):6-10.9. McKibbon KA, Lokker C, Wilczynski NL, et al. A cross-sectional study of the number and frequency of terms used to refer to knowledge translation in a body of health literature in 2006: a Tower of Babel?.Implement Sci. 2010;5:16-16.10. Gervais M-J, Marion C, Dagenais C, Chiocchio F, Houlfort N. Dealing with the complexity of evaluating knowledge transfer strategies: Guiding principles for developing valid instruments. Research Evaluation.2015;25(1):62-69.11. The Canadian Institutes of Health Research. 2016; https://cihr-irsc.gc.ca/e/29418.html. Accessed 22. February, 2020.12. Greenhalgh T, Wieringa S. Is it time to drop the ’knowledge translation’ metaphor? A critical literature review. J R Soc Med.2011;104(12):501-509.13. Kothari A, Wathen CN. A critical second look at integrated knowledge translation. Health Policy. 2013;109(2):187-191.14. Engebretsen E, Sandset TJ, Ødemark J. Expanding the knowledge translation metaphor. Health Res Policy Syst. 2017;15(1):19-19.15. Kreindler SA. Advancing the evaluation of integrated knowledge translation. Health Res Policy Syst. 2018;16(1):104-104.16. Grimshaw JM, Eccles MP, Lavis JN, Hill SJ, Squires JE. Knowledge translation of research findings. Implement Sci. 2012;7:50-50.17. Grol R, Grimshaw J. From best evidence to best practice: effective implementation of change in patients’ care. Lancet.2003;362(9391):1225-1230.18. Green LA, Seifert CM. Translation of research into practice: why we can’t ”just do it”. J Am Board Fam Pract. 2005;18(6):541-545.19. Oliver K, Innvar S, Lorenc T, Woodman J, Thomas J. A systematic review of barriers to and facilitators of the use of evidence by policymakers. BMC health services research. 2014;14(1):2.20. Lavis JN, Oxman AD, Lewin S, Fretheim A. SUPPORT Tools for evidence-informed health Policymaking (STP) 3: Setting priorities for supporting evidence-informed policymaking. Health Res Policy Syst. 2009;7 Suppl 1(Suppl 1):S3-S3.21. World Health Organization. Innovative care for chronic conditions: Building blocks for actions: global report. 2002. Google Scholar.2016.22. Pope C, Ziebland S, Mays N. Qualitative research in health care. Analysing qualitative data. BMJ. 2000;320(7227):114-116.23. Barnett-Page E, Thomas J. Methods for the synthesis of qualitative research: a critical review. BMC Medical Research Methodology.2009;9(1):59.24. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS medicine. 2009;6(7):e1000097.25. Shea BJ, Reeves BC, Wells G, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ (Clinical research ed). 2017;358:j4008.26. La Torre G, Backhaus I, Mannocci A. Rating for narrative reviews: concept and development of the International Narrative Systematic Assessment tool. La Torre G, Backhaus I, Mannocci A/Senses Sc.2015;2(2):31-35.27. Golden SD, Earp JAL. Social ecological approaches to individuals and their contexts: twenty years of health education & behavior health promotion interventions. Health Education & Behavior.2012;39(3):364-372.28. Edwards A, Zweigenthal V, Olivier J. Evidence map of knowledge translation strategies, outcomes, facilitators and barriers in African health systems. Health Res Policy Syst. 2019;17(1).29. Légaré F, Ratté S, Gravel K, Graham ID. Barriers and facilitators to implementing shared decision-making in clinical practice: Update of a systematic review of health professionals’ perceptions. Patient education and counseling. 2008;73(3):526-535.30. Sadeghi-Bazargani H, Tabrizi JS, Azami-Aghdash S. Barriers to evidence-based medicine: a systematic review. Journal of Evaluation in Clinical Practice. 2014;20(6):793-802.31. Shayan SJ, Kiwanuka F, Nakaye Z. Barriers associated with evidence‐based practice among nurses in low‐ and middle‐income countries: a systematic review. Worldviews on Evidence-Based Nursing. 2019;16(1):12-20.32. Athanasakis E. Nurses’ research behavior and barriers to research utilisation into clinical nursing practice: a closer look.International Journal of Caring Sciences. 2013;6(1):16-28.33. Derman RJ, Jaeger FJ. Overcoming challenges to dissemination and implementation of research findings in under-resourced countries.Reproductive Health. 2018;15(1):86.34. Kalassian KG, Dremsizov T, Angus DC. Translating research evidence into clinical practice: new challenges for critical care. Crit Care. 2002;6(1):11-14.35. Lawrence LM, Bishop A, Curran J. Integrated Knowledge Translation with Public Health Policy Makers: A Scoping Review. Healthcare Policy. 2019;14(3):55-77.36. Woolf SH, Purnell JQ, Simon SM, et al. Translating evidence into population health improvement: strategies and barriers. Annual review of public health. 2015;36:463-482.37. Ma TK, Lam YY, Tan VP, Yan BP. Variability in response to clopidogrel: how important are pharmacogenetics and drug interactions?British journal of clinical pharmacology. 2011;72(4):697-706.38. Wallis L. Barriers to implementing evidence-based practice remain high for U.S. nurses: getting past ”we’ve always done it this way” is crucial. The American journal of nursing. 2012;112(12):15.39. Curtis K, Fry M, Shaban RZ, Considine J. Translating research findings to clinical nursing practice. Journal of clinical nursing. 2017;26(5-6):862-872.40. Bahadori M, Raadabadi M, Ravangard R, Mahaki B. The barriers to the application of the research findings from the nurses’ perspective: A case study in a teaching hospital. Journal of education and health promotion. 2016;5:14-14.41. Curtis K, Fry M, Shaban RZ, Considine J. Translating research findings to clinical nursing practice. 2017;26(5-6):862-872.42. Van der Graaf P, Francis O, Doe E, Barrett E, O’Rorke M, Docherty G. Structural approaches to knowledge exchange: comparing practices across five centres of excellence in public health. Journal of Public Health. 2018;40(suppl_1):i31-i38.43. Kothari A, Wathen CN. Integrated knowledge translation: digging deeper, moving forward. Journal of epidemiology and community health. 2017;71(6):619-623.44. Ongolo-Zogo P, Lavis JN, Tomson G, Sewankambo NK. Assessing the influence of knowledge translation platforms on health system policy processes to achieve the health millennium development goals in Cameroon and Uganda: a comparative case study. Health policy and planning.2018;33(4):539-554.45. Oxman AD, Vandvik PO, Lavis JN, Fretheim A, Lewin S. SUPPORT Tools for evidence-informed health Policymaking (STP) 2: Improving how your organisation supports the use of research evidence to inform policymaking. Health Res Policy Syst. 2009;7 Suppl 1(Suppl 1):S2.46. Dobbins M, Robeson P, Ciliska D, et al. A description of a knowledge broker role implemented as part of a randomised controlled trial evaluating three knowledge translation strategies. Implement Sci.2009;4:23.47. Haynes AS, Derrick GE, Redman S, et al. Identifying trustworthy experts: how do policymakers find and assess public health researchers worth consulting or collaborating with? PLoS One.2012;7(3):e32665.48. West RM, House AO, Keen J, Ward VL. Using the structure of social networks to map inter-agency relationships in public health services.Social science & medicine (1982). 2015;145:107-114.49. Cairney P, Oliver K. Evidence-based policymaking is not like evidence-based medicine, so how far should you go to bridge the divide between evidence and policy? Health Res Policy Syst.2017;15(1):35.50. Farquhar CM, Stryer D, Slutsky J. Translating research into practice: the future ahead. International Journal for Quality in Health Care. 2002;14(3):233-249.

Flux experiments and fluorescence microscopy were combined and optimized to visualize the membrane surface during biofouling of two mixed cellulose ester membranes. Using flux measurements, the fouling by bovine serum albumin (BSA) was measured in the presence of 1 to 12% labeled BSA. By fitting the relative flux decays to an exponential decay for statistical analysis, the dye in this range of labeled protein was found to not affect the fouling nature of the protein. A 2.5% or 5% labeled protein sample was determined to be the best percent labeled protein for fluorescence imaging the membrane because the beginning of cake formation was observed within 25 min of experimental time. Finally, by fitting the flux data to four different biofouling mechanism equations, we conclude that both membranes, though at different rates, have BSA depositing inside the membrane pores restricting the flow eventually leading to cake formation. The combination of the two techniques allows for further insight into the biofouling mechanism of BSA, and this method can be applied to other biological molecules.

To the Editor, Drug provocation test (DPT) is considered the gold standard test to diagnose drug hypersensitivity reactions (DHR), in absence of contraindications. However, it may be very time consuming. The procedure usually consists in the administration of a medication with cautious incremental doses under close medical observation.1-4Vital sign measurements (e.g., blood pressure (BP), pulse) and surveillance of the patient’ symptoms and signs are usually performed several times during the entire procedure to capture and prevent as soon as possible any severe reaction. However, learned societies only set a frame for DPT performance and do not make specific recommendations about the type and rhythm of these measurements.1, 3, 4 In our center, data-driven DPT (i.e., based on patterns of reactions detected through Kaplan Meier curves) is performed in 4-7 step dosing for beta-lactams (BL),5 2-6 steps for nonsteroidal anti-inflammatory drugs (NSAID),6 3-4 steps for paracetamol,7 and 5-7 steps for fluoroquinolones (article in press), with time increments of 30 or 60 minutes (up to 3h for certain NSAID). The BL pattern is generally applied to DPTs for other drugs. Empirically, we considered the measurement of BP and pulse as mandatory and required before starting the DPT, before every incremental dose and at any time during the DPT if symptoms of a DHR occurred. We presumed this would ensure the best safety for patients undergoing DPT, particularly for those with immediate severe reactions, namely anaphylaxis with or without shock. However, the benefit of such an attitude in patients with non-immediate reactions or immediate non-severe reactions could be questioned and to the best of our knowledge, no study has been published on this issue. In addition, measurement of BP during ST is not common practice.During the past two decades of our center experience, based on clinical observation and previous analyses,8, 9 we observed that isolated symptoms and signs evocative of shock during drug allergy work-up are very rare. Patients usually presented those signs in conjunction with symptoms and signs from other systems, including mucocutaneous (CU), respiratory (RS), and gastrointestinal (GI). Therefore, we hypothesized that BP measurement could be reduced in number in some circumstances, according to risk stratification (that we presumed related to the patient’s individual situation and involved drug class). This retrospective analysis was then carried out in order to identify cases with symptoms and signs evocative of shock during drug allergy investigation in our center. The patients (or their parents, in case of children) gave their written informed consent at the time of the allergy work-up for their anonymous data to be used for research purposes.We conducted a retrospective analysis using data retrieved from the Drug Allergy and Hypersensitivity Database (DAHD) between January 1996 and June 2019 in the Allergy Unit of the University Hospital of Montpellier, France. Patients with suspicions of DHR who underwent drug allergy work-up and presented with symptoms and signs evocative of shock during the tests were included in the analysis. The search terms included: “malaise”, “hypotension”, “collapse”, “loss of consciousness”, and “unspecified cardiovascular problem”. Drug allergy work-up including skin test (ST) and DPT was performed according to the European Network of Drug Allergy (ENDA) recommendations.During the study period, 10 198 patients were tested with 53 059 single tests (a single test is defined as ST or DPT for an allergen). A total of 32 patients (0.3%) (9 males, mean age at tests of 37.0 ± 14.9 years) with 36 reactions (0.06%) who presented with the above mentioned cardiovascular (CV) signs/symptoms were identified (31 during DPT, 5 during ST). Antibiotics were the most frequent drug classes involved (47.2%), followed by NSAIDs (13.9%), and paracetamol (13.9%) (Supplementary Table 1 ). Among these reactions, 4 were found to be isolated CV signs/symptoms (3/11000 DPT (0.03%), and 1/42059 ST (0.002%), while CV with other systemic signs/symptoms were present in 32 reactions (88.9%). (Table 1 and Supplementary Text 1) Using retrospective analysis from the DAHD during the past 25 years, we have demonstrated that patients with CV symptoms and signs evocative of a severe immediate DHR (shock) during the drug allergy investigation are rare, namely 0.3% of all tested patients and 0.06% of all single tests. Amongst them, only 4 patients (0.04%) with 4 reactions (0.007%) were found to have isolated CV signs/symptoms. Whether these signs were markers of true DHR could be debatable for patients no. 1 (considering her multiple similar episodes, ruled out by further investigations) and no. 3 , while patient no. 4 developed anaphylactic shock during positive ST to BL drugs (meaning that the systemic symptoms were associated to positivity at the injection site). Therefore, only one case (patient no. 2) could be classified as having isolated CV signs/symptoms as an allergic reaction.Based on this analysis and previous analyses of patterns of reactivity and severity during DPT for different drug classes (e.g., BL, NSAIDs, paracetamol, quinolones), we propose criteria to reduce the frequency of BP measurements during DPT, according to risk stratification based on patient clinical history and drug class. Clinical history could be classified into three categories: immediate severe (high risk), immediate non-severe (low risk), and non-immediate non-severe (low risk) reactions (i.e., severe non-immediate reactions being classical contraindications to DPT).3 Regarding drug class, we based our risk stratification on previous studies tackling patterns of DPT reactions to BL, NSAIDs, paracetamol and quinolones showing that the frequency of anaphylaxis elicited by DPT was 15%, 10%, 25% and 20% respectively.5-7 For NSAIDs, the immediate non-severe reaction (e.g., urticaria, angioedema, rhino-conjunctivitis) is a typical clinical presentation and for such an index reaction, 90% of the positive DPT are benign cutaneous reactions (6). Thus, NSAIDs could be classified as low risk drug class. Therefore, the criteria of BP measurement could be categorized as in Table 2. Regarding our 4 patients with isolated CV symptoms, all of them would’ve been classified in the high-risk groups (patient no. 1 and no. 3 because of index history of immediate severe reaction, patient no. 2 and no. 4 because of the drug class).It could be argued that by reducing the number of CV vital signs measurements, the professional performing the DPT could be distracted from the very core of the allergy work-up, which is ensuring patient safety during the procedures. However, our study shows that isolated CV signs/symptoms are extremely rare during the drug allergy work-up performed according to safety recommendations (i.e., step-wise exposure to allergen). In contrast, the decrease in this technical workload could be beneficial to patients because physicians/nurses would then have more time to concentrate on patient questioning and reassurance during the tests. In addition, the reduction of this measurement could reduce the uncomfortable, or painful feeling of the BP measurement, particularly for young children.To the best of our knowledge, this is the first study specifically addressing the outcome of the BP measurement during drug allergy work-up in an evidence-based manner. Reporting and analyzing the rarity of cases with isolated CV signs/symptoms enabled us to propose 4 frames for BP measurement. In a prospective trial for 1 month, BP frequency could be reduced by 14.3% (range 10.3-26.5), alleviating the technical task and favoring the medical one instead. The prospective evaluation is ongoing in our center.In conclusion, patients with symptoms and signs evocative of shock are extremely rare during drug allergy work-up, therefore BP measurement could be reduced in number according to patient clinical history of DHR and drug class risk stratification.

A novel bioinformatic approach for drug repurposing against emerging viral epidemics like Covid-19 is described. It exploits the COMPARE algorithm, a public program from the NCI to sort drugs according to their patterns of growth inhibitory profiles from a diverse panel of human cancer cell lines. The data repository of the NCI includes the growth inhibitory patterns of more than 55000 molecules. When drugs with purported anti-SARS-CoV-2 activities were used as seeds (e.g., hydroxychloroquine and ritonavir) in COMPARE, the analysis uncovered several drugs with fingerprints similar to the seeded drugs. Interestingly, the uncovered drugs were all reportedly known to exert antiviral activities, confirming that COMPARE analysis is valuable for predicting antiviral drug repurposing. Unlike pure in-silico approaches, this approach is biologically more relevant and able to pharmacologically correlate compounds regard-less of their structures. This is an untapped resource, reliable and readily exploitable for drug repurposing against surprising viral outbreaks.

Background and Purpose: The immune system is implicated in the pathogenesis of pathological cardiac hypertrophy (PCH). However, there is currently no therapeutic intervention to prevent PCH. Here, we aimed at preventing pathological cardiac hypertrophy (PCH) during chronic catecholamine stress via modulating adaptive inflammatory by targeting adenylyl cyclases (ACs) and G protein-coupled receptor kinase 5 (GRK5) in cardiomyocytes and immune cells. Experimental Approach: PCH was induced in mice by chronic isoproterenol injections. In vitro, peritoneal macrophages were challenged with lipopolysaccharide under stress. Further experiments employed the therapeutic interventions Amlexanox and Forskolin to inhibit GRK5 and activate ACs-cAMP, respectively. Cardiac functions were assessed with echocardiography. Inflammatory markers were assessed with ELISA and RT-qPCR (in vivo and in vitro). GRK5 localizations in macrophages were assessed by immunofluorescence, and alterations in protein expression were analyzed with immunoblotting. Histological assessments were done with Masson, H&E and IHC staining. Key Results: PCH mice had deteriorating cardiac functions and morphological remodeling, accompanied by massive immune cell infiltrations. Similarities were observed proinflammatory markers upregulation, as were IL-10 found downregulated both in vivo and in vitro. However, the combination of Amlexanox and Forskolin modulated adaptive inflammatory responses and also maintained proper cardiac morphology and function. The single therapies of neither Amlexanox nor Forskolin were able to attain the aforementioned with much efficacy as their combination therapy. Conclusion: The combination therapy of ALX and FSK has the therapeutic potential of preventing the occurrence of pathological cardiac hypertrophy during CCS by modulating adaptive inflammatory responses while maintaining normal cardiac function.

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage were associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin converting enzyme 2 (ACE2). As a result of SARS-Cov-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT1R) axis associated with oxidative stress. This leads to insulin resistance, lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block the AT1R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects helpful in mitigating COVID-19 severity.

Plasticity in salt tolerance can be crucial for successful biological invasions of novel habitats by marine gastropods. The intertidal snail Batillaria attramentaria, which is native to East Asia but invaded the western shores of North America from Japan eighty years ago, provides an opportunity to examine how environmental salinity may shape behavioral and morphological traits. In this study, we compared the movement distance of four B. attramentaria populations from native (Korea and Japan) and introduced (USA) habitats under various salinity levels (13, 23, 33, and 43 PSU) during 30 days of exposure in the lab. We sequenced a partial mitochondrial CO1 gene to infer phylogenetic relationships among populations and confirmed two divergent mitochondrial lineages constituting our sample sets. Using a statistic model-selection approach, we investigated the effects of geographic distribution and genetic composition on locomotor performance in response to salt stress. Snails exposed to acute low salinity (13 PSU) reduced their locomotion and were unable to perform at their normal level (the moving pace of snails exposed to 33 PSU). We did not detect any meaningful differences in locomotor response to salt stress between the two genetic lineages or between the native snails (Japan versus Korea populations), but we found significant locomotor differences between the native and introduced groups (Japan or Korea versus the USA). We suggest that the greater magnitude of tidal salinity fluctuation at the USA location may have influenced locomotor responses to salt stress in introduced snails.

Background and Purpose: Hypertensive vascular remodeling (VR) is responsible for end-organ damage and is the result of increased extracellular matrix accumulation and excessive vascular smooth muscle cell (VSMC) proliferation. MicroRNA-26a (miR-26a), a non-coding small RNA, is involved in multiple cardiovascular diseases. We aimed to validate the effect and mechanisms of miR-26a in hypertensive VR. Experimental Approach: Spontaneously hypertensive rats (SHRs) were injected intravenously with recombinant adeno-associated virus-miR-26a. In vitro experiments, angiotensin II (AngII)-induced VSMCs were transfected with miR-26a mimic or inhibitor. Key Results: We found miR-26a downregulated in the thoracic aorta and plasma of SHRs. Overexpression of miR-26a inhibited extracellular matrix deposition by targeting connective tissue growth factor (CTGF) and mitigated VSMC proliferation by regulating the enhancer of zeste homolog 2 (EZH2)/p21 pathway both in vitro and in vivo. AngII-mediated Smad3 activation suppressed miR-26a expression, which in turn promoted Smad3 activation via targeted regulation of Smad4, leading to further downregulation of miR-26a. Conclusion and Implications: Our study reveals that AngII stimulates a Smads/miR-26a positive feedback loop, which further reduces miR-26a expression, leading to collagen production and VSMC proliferation and consequently, VR. MiR-26a has an antagonistic effect on hypertensive VR and can be a strategy for treating hypertensive VR.

Endometriosis is a common health condition affecting women of reproductive age who often present with chronic pelvic pain and/or infertility. There is wide variation in the estimates of endometriosis prevalence. Accurate reporting of the disease prevalence is hampered by multiple factors including long delay in diagnosis due to natural fluctuation in symptoms severity, lack of a reliable non-surgical diagnostic tool, polymorphic appearance of endometriosis lesions at laparoscopy, inability to achieve histological confirmation is all suspected cases and tendency for disease recurrence. Therefore, a longitudinal, rather than cross-sectional, cohort study design spanning an extended follow-up period is better suited to assess endometriosis prevalence. In this issue of BJOG, Rowlands and colleagues (2020) linked longitudinal survey data to three administrative health databases to identify the prevalence of endometriosis among 13,508 young Australian women followed up for nearly 20 years. The study reported a 6% cumulative prevalence of clinically-confirmed endometriosis and an additional 5.4% of clinically-suspected endometriosis. If these figures reflect the true prevalence of endometriosis, then one in nine women will be diagnosed with endometriosis at some point during their reproductive years up to the age of 44 with a peak at 30-34 years, thus underscoring the significant impact of the disease on the well-being and quality of life in young women and the enormous burden on healthcare resources needed to diagnose and treat endometriosis and its sequelae.The data presented in the study of Rowlands and colleagues (BJOG 2020) included patients who could have been diagnosed with adenomyosis but their condition was coded as endometriosis. This is unlikely to have significantly over-estimated the prevalence of endometriosis as recent evidence suggests adenomyosis prevalence to be only 1% with a considerable proportion of those patients having co-existing endometriosis (Yu et al, Am J Obstet Gynecol 2020; 223: 94.e1-10). The same can not be said about the 5.4% of clinically-suspected endometriosis cases. Symptoms review, clinical examination and various imaging modalities, including ultrasound scanning and magnetic resonance imaging, represent the cornerstone of non-invasive diagnosis of endometriosis. Current evidence suggests that the predictive accuracy of those non-invasive methods in the diagnosis of endometriosis compared to laparoscopy and histological confirmation is modest (Nisenblat et al, Cochrane Database Syst Rev, 2016 (2): CD009591) and depends on the combination of diagnostic tools used as well as the site and extent of the endometriosis lesions (Reid et al, Eur J Obstet Gynecol Reprod Biol 2019; 234: 171-178). These data are not provided in the study of Rowlands and colleagues. It is therefore difficult to accurately estimate the prevalence of endometriosis whether it’s the 6% clinically-confirmed rate or the full 11.4% confirmed and suspected rate. The truth probably lies somewhere in the middle! Future epidemiological studies should endeavour to elucidate on the distinction between the different methods used in the diagnosis of endometriosis with reference to the predictive accuracy of each diagnostic modality to help advance our understanding of the incidence and risk factors associated with this debilitating gynaecological condition.Mr. Tarek A El-ToukhyAssisted Conception Unit, Guys and St. Thomas Hospital NHS Trust11th Floor, Tower Wing,Guys Hospital,St. Thomas Street tarekeltoukhy@hotmail.com

To the Editor,The proportion of the population with allergic diseases has increased rapidly in recent decades1, 2. In addition to affecting the quality of life, a significant economic burden of these diseases was transferred to society and the national health care system1. China is a large country with a rapidly developing economy, wide geography, and diverse climate and lifestyles, which may lead to significantly regional differences in the distribution of allergens. Although a series of studies have explored the prevalence of allergen sensitization in China, the majority of them focus on one part of geography in China3-5. In 2009, a study6 was conducted to estimate the prevalence of common aeroallergens among patients with allergic asthma and/or rhinitis in mainland China. Although the study investigated the differences of the prevalence in different regions of China, it divided China into only four geographical regions, which may neglect detailed information about the characteristics of sensitization prevalence in different places in China. In that study, the skin prick test (SPT) was used to detect the sensitization to allergens. The method has low accuracy for positive results because it is heavily affected by certain factors, such as the skill of the tester, reagent used, interpretation of results and so on. Our research has the following different characteristics compared with previous studies: 1) covering a variety of allergic diseases, 2) exploring both aeroallergens and food allergens simultaneously, 3) including a large set of data from all the seven regions of mainland China, and 4) using an internationally recognized method of sIgE testing, ImmunoCAP, to detect sensitization. These advantages may help us obtain more accurate and reliable results and conclusions.Here, we conducted a large multicenter study on the prevalence patterns of serum allergen-specific IgE (sIgE) sensitization to the four most common food allergens (i.e., egg whites, cow’s milk, crab, and shrimp) and five aeroallergens (i.e., house dust mite, German cockroach, tree pollen mix, mold mix, dog dander) among 44156 patients with allergic symptoms in 52 cities from 26 provinces of all the seven geographical regions in mainland China from July 2015 to June 2018. The sIgE sensitization was tested by a certified third-party laboratory service provider with uniform and standardized procedures. This study was approved by the ethics committee of the First Affiliated Hospital of Guangzhou Medical University (Approval number: GYFYY-2017-18). Details about the methods were in the supplementary materials .Our study showed that the overall prevalence of positive sIgE responses to the 9 allergens across mainland China from the highest to the lowest was 33.74% for house dust mites, 24.5% for cockroaches, 19.97% for shrimp, 17.31% for crab, 11.62% for cow’s milk, 10.92% for egg whites, 9.35% for tree pollen mix, 4.02% for dog dander and 3.92% for mold mix (Table 1 ). Our study confirmed that an observation shown in several previous studies based on certain specific areas in China3-5 that the positive cases in sIgE fell mainly in the two low classes (i.e., classes 1 and 2) was also held in all the seven regions in mainland China (Table 1 ).Our study revealed the distinctive patterns in the prevalence of allergen sensitization among regions, gender, age groups and seasons. Geographically, there is a significant difference in the prevalence among regions for all 9 allergens except for the mold mix (Table S1 ). House dust mites were the allergen with the highest prevalence of sensitization in all seven regions, with the highest in South China (40.79%) and the lowest in Northeast China (11.21%). Allergies to German cockroaches had a higher prevalence in southern regions (Southwest China, South China and East China) than in northern regions (North China and Northeast China). The prevalence of sIgE responses to dog dander was the highest in North China and was very close to each other in the southern regions. The prevalence of the egg whites and milk in Central China, East China and South China was higher than in Southwest China, North China and Northeast China, which means that patients living in eastern, coastal and/or southern areas were more sensitive to egg whites and cow’s milk. The prevalence of crab and shrimp sensitization in Southwest China and South China was higher than that in the northern regions (North China and Northeast China). The heatmap (Figure 1 ) displays the distribution of the prevalence of the sIgE response to allergens in different regions of mainland China.The prevalence of sensitization to all nine allergens was higher overall in males than in females (Table 1 and Figure S1 ) although that may not be true in each age group for each allergen as shown in the forest plot in Figure S1 . Our study showed that, whereas the sensitization to egg whites and milk was the highest in children, the sensitization to other allergens tended to be the highest in teenagers and young adults (Figure S2 ). Figure S3displays he prevalence pattern of allergens by months across years. The prevalence of dog dander and mold mix was very stable across months; however, the prevalence of other allergens fluctuated from January to December. The prevalence of house dust mites, German cockroach, shrimp and crab were higher in the summer months (from June to August) than in other months. The prevalence of tree pollen mix was much higher in April and October than in other months.This should be the first large study to investigate the prevalence of allergen sensitization in the patients with allergic symptoms from all the seven geographic regions of mainland China. Based on this study, we found that the prevalence of sIgE sensitization to allergens displayed obvious and distinctive patterns among regions, gender, age groups and seasons. The reasons for these patterns may include lifestyle factors, socioeconomic factors, genetic predispositions, climate, sexual hormones, cross-reactivity and so on3,4,6-9. Please refer to the supplementary materials for the detailed discussion on the factors that influenced these variations. Our findings may help clinicians find effective individualized treatments for unique patient groups and direct researchers to conduct further studies on the epidemiology of allergic diseases.

Background In asthma, the decrease of pulmonary function and occurrence of pulmonary inflammation are largely attributed to the increase of airway vagal activity, of which the genesis involves disrupted degradation of central extracellular ATP to adenosine due to decreased expression and activity of ecto-5’-nucleotidase (CD73). Meanwhile, the therapeutic use of statins reportedly is able to alleviate asthma; however, the mechanisms remain unclear. This study test whether rosuvastatin is able to attenuate the downregulation of central CD73 and, subsequently, attenuate the increase of airway vagal activity in the rat model of allergic asthma. Methods An experimental rat model of allergic asthma was prepared using ovalbumin. During the sensitization period, ovalbumin was inhaled alone or in combination with rosuvastatin. Plethysmographic measurement of pulmonary function was used to evaluate airway vagal activity; molecular biological assay was used to examine the expression and activity of medullary CD73 and the expression of eosinophil cationic protein 1 (ECP1) in the lungs. Results In ovalbumin-sensitized rats, the decreases in the expression and activity of medullary CD73 and the increases in the expression of ECP1 in the lungs and ATP concentration in cerebral spinal fluid were completely reversed by inhaled rosuvastatin, so was the increase of airway vagal activity manifested by the atropine-sensitive increase of airway resistance and decrease of airway compliance. Conclusions In the rat model of allergic asthma, inhaled rosuvastatin reverses the decreases in the expression and activity of brainstem CD73, which prevents pulmonary function decrease via an abolished increase of airway vagal activity.

Background: Ultrasound-guided percutaneous core needle biopsy (PCNB) has been used more and more frequently in diagnostics of pediatric solid tumors in our center. It is less invasive than an incisional biopsy. However, reports relating to its reliability in clinical practice are limited. Therefore, we aim to investigate the reliability of this technique in the pediatric population. Methods: A 7-year retrospective study including patients ≤ 18 years who underwent ultrasound-guided PCNB in our center was conducted. Children who received PCNB and final surgical treatment were included. Their medical records were reviewed. Final surgical pathological diagnoses were used as the gold standard to assess the diagnostic efficiency of PCNB. Results: A total of 169 children were included in our analysis. 87.0% of patients underwent PCNB for abdominal and pelvic masses. 79.1% of biopsies were performed under local anesthesia. There were 141 malignancies and 28 benign lesions confirmed by surgery. The most common malignancy was neuroblastoma (73), and the most common benign condition was fibromatosis. The diagnostic yield was 94.1%. The success rate of PCNB in determining benign and malignant conditions was 94.3% (150/159). Consistency between PCNB and final diagnoses was found in 143 cases, giving a total accuracy of 89.9%. The accuracy for diagnosing malignancies was 96.8% (122/126), and for benign diseases 87.5% (21/24). The difference was not statistically significant (p=0.0818). Severe complications occurred in 6 patients (3.5%). No evidence of needle tract dissemination was found. Conclusions: Ultrasound-guided PCNB is safe and effective in diagnosing pediatric solid tumors, especially in malignancies.

Pine wilt disease (PWD), Bursaphelenchus xylophilus, is an extremely threatening invasion forest disease throughout the world, especially in Asia. B. xylophilus is spread in Asia by vector beetles of Monochamus alternatus, which has long no effective control method. Understanding of landscape effects on the dispersal and outbreaks of forest pests is crucial to establishing effective ecological control strategies. Here, we analyzed the samples of M. alternatus collected at landscapes in order to estimate the effects of landscape types on the genetic structure and dispersal of M. alternatus. The landscapes included the geographical scales, forest types and land uses. The individuals of M. alternatus were genotyped by using whole-genome resequencing. Population genetic structures were clearly differentiated at the intermediate scale, suggesting the intermediate scale is an effective barrier against natural dispersal of M. alternatus. We used the least-coat distances, least-cost transect analysis, and distance-based redundancy analysis to estimate the effects of forest types and land uses within the fine scales. The results showed that the gene flow and genetic diversity were positively correlated with host and mixed forests, whereas negatively with non-host forests. Among land-use landscapes, the roads had the positive effect on gene flow and genetic diversity but farmland and urban uses had negative effects. This highlights that human-mediated transport via roads was likely to be the main factor leading to the long-distance invasion of M. alternatus, whereas non-host landscapes could suppress the spread of this species. These findings may be useful to control the PWD dispersed by M. alternatus.

Introduction: In patients with post-infarct cardiomyopathy and ventricular arrhythmias (VT) necessitating implantable cardioverter defibrillators (ICD) are at risk of recurrent shocks with increased morbidity. Methods and Results: A comprehensive search of electronic databases for all randomized clinical trials that evaluated the role of catheter ablation as a preventive strategy at the time of secondary prevention ICD implantation was performed. Four trials were identified with a total of 505 patients (average age 66.4 ± 9.0 yr; 87.7% were male). Preventive ablation was associated with a significant reduction in appropriate device therapies (shocks and/or anti-tachycardia therapy) (hazard ratio [HR]=0.62; 95% confidence interval [CI]=0.46-0.82; p<0.01), sustained VT (HR=0.74; 95% CI=0.55-0.99; p=0.04) compared to control. There were no differences in inappropriate device shocks (HR=0.80; 95% CI=0.38-1.71), all-cause death (HR=0.93; 95% CI=0.53-1.64), cardiac death (HR=0.63; 95% CI=0.29-1.36), arrhythmic death (HR=0.26; 95% CI=0.05-1.31), or cardiac hospitalization (HR=0.79; 95% CI=0.57-1.11) between strategies. Preventive ablation was associated with improved SF-36 physical component (SMD=2.81; 95% CI-0.53-5.10; p=0.02), but not the mental component (SMD=1.30; 95% CI=-2.06-4.66). Conclusion: Among patients with post-infarct cardiomyopathy and VT, preventive catheter ablation at the time of ICD implantation is associated with a significant reduction of appropriate ICD therapy and sustained VT, and improvement in the physical component of quality-of-life, but no reduction in mortality.

Background: Radiofrequency catheter ablation (RFCA) as a safe and effective method has been widely used in ventricular tachycardia (VT) patients, and with which anesthesiologists frequently manage their perioperative care. However, the procedure and prognosis may be affected by the use of anesthetics. Objectives: The aim of this study was to investigate the effects of different anesthetic depths on perioperative RFCA and recurrence in patients who with intractable VT and could not tolerate an awake procedure. Methods: We performed a retrospective study of all patients with a confirmed diagnosis of VT and underwent RFCA by general anesthesia from January 2014 to March 2019. According to intraoperative VT induction, they were divided into 2 groups: non-inducible group and inducible group. We constructed several multivariable regression models, in which covariates included patient characteristics, comorbidities, protopathy and BIS value.  Results: We included 101 patients, 29 (28.7%) of whom experienced VT no induction, and 26 (26.3%) recurrence within one year. Based on pre-specified bispectral index (BIS), the BIS <40 was associated with elevated odds of VT no induction compared with a BIS value >50 (odds ratio, 6.92; 95% confidence interval, 1.47-32.56; P=0.01). VT no induction was an independent predictor of recurrence after RFCA (odds ratio, 5.01; 95% confidence interval, 1.88-13.83; P<0.01). Conclusions: This study reported lower BIS value during VT induction was associated with high risk of the failure of VT induction, which in turn affects postoperative outcomes. We propose that appropriate depth of anesthesia should be maintained during the process of  VT induction.

Background: The abnormal conduction zone (ACZ) in the left atrium (LA) has attracted attention as an arrhythmia source in atrial fibrillation (AF). We investigated the hypothesis that the ACZ is related to the low voltage area (LVA) or the LA anatomical contact areas (CoAs) with other organs. Methods and Results: We studied 100 patients (49 non-paroxysmal AF, 66 males, 67.9±9.9 years) who received catheter ablation for AF. High-density LA mapping during high right atrial pacing was constructed. Isochronal activation maps were created at 5-ms interval setting, and the ACZ was identified on the activation map by locating a site with isochronal crowding of ≥3 isochrones, which are calculated as ≤27 cm/s. The LVA was defined as the following; mild (<1.3 mV), moderate (<1.0 mV), and severe LVA (<0.5 mV). The CoAs (ascending aorta-anterior LA, descending aorta-posterior LA, and vertebrae-posterior LA) were assessed using computed tomography. The ACZ was linearly distributed, and observed in 95 patients (95%). The ACZ was most frequently observed in the anterior wall region (77%). A longer ACZ was significantly associated with a larger LA size and a prevalence of non-PAF. The 51.2±36.2% of ACZ overlapped with mild LVA, 32.9±32.8% of ACZ with moderate LVA, and 14.6±22.0% of ACZ with severe LVA. In contrast, only 25.6±28.0 % of ACZ matched with the CoAs. Conclusion: The abnormal conduction zone reflects LA electrical remodeling and may be a precursor finding of the low voltage zone and not the LA contact areas in patients with atrial fibrillation.

The endothelium plays a critical role in determining vascular tone. Endothelial dysfunction is characterized by an imbalance between endothelium derived vasodilating and vasoconstricting effects (1). Forearm artery endothelial function measured non-invasively is commonly used as a surrogate marker for endothelial function of the coronary arterial circulation (2) and has been used to assess the effect of atrial fibrillation on peripheral arterial function. Studies have demonstrated that atrial fibrillation is associated with endothelial dysfunction of forearm arteries, which improves after successful electrical cardioversion (3) or catheter ablation (4). Measurements of endothelial function have often focused on flow within the larger conduit arteries as opposed to the microcirculation. Most studies used post occlusive reactive hyperemia (PORH) or flow mediated dilation which are in part nitric oxide (NO)-dependent. Microcirculatory endothelial function following AF treatment has not been studied.Laser speckle contrast imaging (LSCI) is a technology that measures blood flow in the skin microvasculature using laser beam light that reflects off moving red blood cells (5). Iontophoresis is a method for non-invasive transdermal drug delivery to the skin microvasculature based on the transfer of charged molecules using a low-intensity electric current (5). We hypothesized that the microvascular endothelial function in AF patients improves after sustaining normal sinus rhythm using antiarrhythmic drugs (AAD). We utilized LSCI to measure change in blood perfusion after brief ischemia-reperfusion (post-occlusive RH [PORH]) and used iontophoresis to transfer vasodilating agents to the skin microcirculation (chemical RH).This prospective cohort study was approved by the University of Pittsburgh Institutional Review Board. All subjects provided written informed consents. We recruited patients with symptomatic AF electively admitted to the inpatient cardiac electrophysiology service for initiation of sotalol or dofetilide. Measurements were repeated during follow up outpatient visits after hospital discharge. Exclusion criteria included age above 75 years old, history of clinical cardiovascular disease, advanced organ failure, major trauma within the preceding 3 months, uncontrolled autoimmune disease, or inflammatory disease.Prior to attaching electrodes, the forearm was gently cleaned with alcohol wipes. The dispersive electrode was attached proximal to the wrist. The drug delivery electrode was attached 10–15 cm from the radial styloid process. Patients were kept in a supine position during the test. After laying down for 15 minutes, their endothelium-dependent vasodilation was assessed using iontophoresis (Perimed Perilont, Järfälla, Sweden) to transmit acetylcholine 1%. Next, we used iontophoresis to transmit sodium nitroprusside 2.5% for the purpose of evaluating the endothelium independent vasodilation. Afterwards, PORH was acquired as a measure of overall vascular function. To this end, we inflated a blood pressure cuff around the patient’s arm to 50 mmHg above systolic blood pressure and deflated the cuff after 5 minutes. The LSCI camera (Perimed PeriScan, Järfälla, Sweden) was placed 20 cm above the forearm. Resting flow (RF) was obtained for 1 minute. Peak flow (PF) was obtained for 2 minutes after iontophoresis and after deflating the blood pressure cuff (post-occlusive RH). We recorded resting flow (RF), peak flow (PF) and calculated RH [(PF-RF)/RF].We enrolled 12 patients with a median age of 69 (65-70) years (33% men). Patients had a median BMI of 34 (28-36) kg/m2and a median CHADVASC score of 3 (IQR 2-3). Twenty five percent of patients had paroxysmal atrial fibrillation. Three patients had moderate to severe LA dilation. Half of the patients were started on sotalol and the other half on dofetilide, as per the choice of the treating electrophysiologist. We conducted this study between July 2019 and June 2020, during which time seven patients had AF recurrence. Two patients with AF recurrence underwent pulmonary vein isolation and their AADs was discontinued. Two other patients were scheduled to undergo ablation but their AADs were continued. Three patients had decreased burden of their symptoms despite recurrence and their AADs were continued.As shown in Table 1, patients with or without recurrence of AF had no significant change in chemical RH or PORH after treatment. RH before starting AADs was not significantly different between patients who had AF recurrence and patients who did not. Patients on sotalol had similar RH to patients to the other study patients at time of follow up.In summary, we found that microvascular endothelial NO dependent function, endothelial NO independent function and PORH did not change in AF patients after the initiation of class III AADs. This was true regardless of whether normal sinus rhythm was maintained or not and for both AADs used. Our study has limitations. The small number of patients limits the statistical power of the data. Also, no continuous heart rhythm monitoring was used in our cohort. Alteration of endothelium derived vasoactive substances, other than NO, in AF requires additional studies. Notwithstanding these limitations, an important finding of this research suggests that atrial fibrillation’s effect on the microcirculation is different from its effect on the larger conduit arteries.

Our article reported risk factors for ICD lead failure at our medical center, and we found an elevated risk of ICD lead failure in multiple lead ICD systems implanted via cephalic venous access.(1) Our analysis was prompted by recent literature related to durability of the Linox ICD lead (Biotronik, Inc., Berlin, Germany), and we found similar, elevated risk of ICD lead failure implanted in multiple lead systems via cephalic access in Linox and non-Linox ICD leads. Given the small number of total lead failures in the overall cohort (6 of 660), and the retrospective, single-center nature of our analysis, we reviewed prior Linox ICD lead durability manuscripts for evidence of increased risk of failure in multiple lead ICD systems implanted via cephalic venous access. While no prior manuscript evaluated this specific risk, we did find a trend towards increased risk of lead failure in cohorts with greater proportions of multiple lead systems, and greater proportions of systems implanted via cephalic access, however these variables were included in the analysis in a minority of prior studies.Dr. Maas and colleagues express surprise at the high failure rate when implanting multiple leads in our cohort. We would clarify that we reported ICD lead failure in 4 of the 304 patients in our cohort with multiple ICD leads, and that the frequency of lead failure in multiple lead ICD systems was not statistically significantly different compared to that of single lead ICD systems. In contrast, and surprisingly to us, 3 of 30 patients with multiple lead ICD systems implanted via cephalic access experienced ICD lead failure, and the frequency of ICD lead failure was significantly greater in this group compared to the remaining cohort in Kaplan-Meier survival analyses.Maas and colleagues question the reason for utilization of cephalic access in 18% of patients, hypothesize that suboptimal implantation technique may be responsible for the elevated lead failure rate, and request clarification of lead failure mechanism. We did not systematically collect rationale for venous access technique, and venous access techniques was at the discretion of the implanting physician. Of the 6 lead failures, 3 were related to lead noise, and 3 were related to rising pacing thresholds. Of the three lead failures amongst patients with multiple lead systems implanted via cephalic venous access, 2 were related to lead noise, and 1 was related to a rising pacing threshold. We believe that the lead noise may be related to insulation breach that may be predisposed by lead-lead interactions in the region of the cephalic vein. ICD leads were returned to the manufacturer on an ad hoc basis, and no specific feedback was received from manufacturers related to leads included in our analysis. All implanting physicians were experienced operators, and there were no significant differences in frequency of ICD lead failure by operator. We agree that implantation technique may play an important role in lead failure risk, and our analysis should prompt extra caution when implanting multiple leads via cephalic venous access.Citing the above limitations of our analysis, Dr Maas and colleagues state that it is “too early to abandon cephalic vein access, even for multiple lead systems.” They also review recent literature reporting favorable acute outcomes of ultrasound guided axillary venous access. We agree that our analysis paired with our literature review is best considered hypothesis generating, and we hope that our analysis encourages future studies to consider our findings when selecting variables of interest in ICD lead durability studies. We share Dr. Maas and colleagues’ favorable view of data supporting axillary venous access, particularly in combination with ultrasound guidance. As a result, given the available evidence of acceptable alternative techniques, our practice is to favor axillary venous access during implantation of multiple lead ICD systems, but we would not hesitate to implant via cephalic venous access in the appropriate clinical scenario.References1. Barbhaiya CR, Niazi O, Bostrom J et al. Early ICD lead failure in defibrillator systems with multiple leads via cephalic access. Journal of cardiovascular electrophysiology 2020;31:1462-1469.

The present case report discusses about a male patient with closed-globe traumatic cataract and isolated posterior capsule rupture. There are limited studies reporting about such type of complication. The management with phacoemulsification and combined pars plana vitrectomy with intraocular lens reverse optic capture was performed.

The effect of pneumatic shot peening (PSP) on the fatigue properties of K403 turbine blades has been investigated under the high and low cycle combined fatigue (CCF) load with two types of blades: untreated blades and PSP treated blades. It is found that there is a threshold vibration stress which should be 194MPa. The PSP has a positive effect on the CCF life of blades mainly due to the compressive residual stress resulting in the reduction of the number of crack sources and propagation rate when vibration stresses are below the threshold vibration stress. However, the PSP treatment has no or negative effect when vibration stresses are above the threshold value. The compressive residual stress is released along with the microstructure changes of K403. Meanwhile, the microstructure changes, reflected in the precipitation of the lamellar MC carbides and σ phases, can accelerate the process of crack initiation and propagation.

Introduction Acute bronchiolitis is the most common respiratory illness and the main cause of respiratory failure in infant. Effective therapy is not available. A relatively new, safe and promising method of non-invasive respiratory support is oxygen delivery by high-flow nasal cannula (HFNC), but several questions concerning HFNC clinical practice remain unanswered. Aim The main aim of our study is to analyse the clinical course of infants hospitalized for bronchiolitis who underwent HFNC in order to identify clinical, laboratory or radiological findings that can have an impact on HFNC failure, which is defined as requirement for mechanical ventilation (MV). Methods We conducted a retrospective data analysis of case records of 130 patients less than 12 months hospitalized for bronchiolitis who underwent HFNC and clinical epidemiological laboratory and radiological data were collected. Results Only 11 (8.5%) out 130 infants required invasive mechanical ventilation for clinical deterioration. Patients who needed to switch from HFNC to MV because of a progressive respiratory failure showed more frequently a complete upper lobe consolidation on CXR (90.9%) than infants exclusively supported by HFNC (14.9%). They were younger with a lower admission weight and they had a lower lymphocyte count than patients who underwent HFNC only. Discussion Our study suggests that a complete upper lobe consolidation in young infants is a significant risk factor for HFNC failure. Further studies are needed to understand if an early identification of consolidation following by an adequate follow-up and proper therapeutic strategies may reduce the number of children who require mechanical ventilation.

Introduction: Asthma is a disease with important morbidity and that can lead to death in childhood. The use of intravenous magnesium sulfate has been indicated in cases refractory to the initial management with inhaled bronchodilators and corticosteroids. Objective: To evaluate the use of magnesium sulfate in continuous infusion (50mg/kg/hour in 4 hours) in children with severe acute asthma. Location: 10-bed pediatric emergency room, university hospital. Patients: Children over 2 years old who received a continuous infusion of magnesium sulfate at a dose of 50mg/kg/hour in 4 hours. Methods and main findings: Cross-sectional, prospective study. All patients with severe acute asthma were included in a study protocol. A total of 40 patients met the inclusion criteria, 60% male, with a median age of 3.0 years (2.8-4.3). All patients were monitored and followed by an emergency pediatrician during the 4 hours of infusion. There was no description of adverse events related to the magnesium sulfate. The modified Wood-Downes clinical score was applied and compared before and after the infusion and a significant clinical improvement was observed (p<0.001). The serum magnesium levels at the end of the infusion ranged from 3.3-5.8 mg/dL, suitable as therapeutic and without toxicity (median 4.0). The median length of stay in pediatric emergency was 2 days. Only 2 patients (5%) were transferred to the PICU. Conclusions: On this study, the use of continuous magnesium sulfate proved to be well tolerated, leading to improved respiratory status, and can be considered as adjunctive therapy in the management of severe asthma.

Introduction: In 2019, an alarming number of cases coined as e-cigarette, or vaping, product use associated lung injury (EVALI) was described in adolescents ranging from mild respiratory distress to fulminant respiratory failure. Limited data has been published on outcomes at short term follow-up. We aimed to describe pulmonary manifestations, function and radiologic findings after corticosteroid therapy in a cohort of adolescent patients. Methods: A retrospective chart review of all patients presenting to our institution between July and December 2019 with EVALI was conducted. Patients who had pulmonary follow-up were included. Spirometry was performed prior to discharge from the hospital and during outpatient follow-up. A paired t-test was used to compare serial spirometry data between visits. Results: Eight patients (6 males) were included. Two patients required intubation with mechanical ventilation, 2 required bilevel positive airway pressure (BPAP), and 3 required oxygen supplementation. All patients received glucocorticoids (3 receiving pulse dosing). Initial spirometry revealed decreased forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) with clinically and statistically significant improvement at follow-up. Diffusing capacity of the lungs for carbon monoxide (DLCO) was decreased in 2/6 patients initially and in 4/5 at follow-up. Radiographic manifestations also improved after vaping was discontinued. Conclusion: In our cohort of patients with EVALI, at short term follow up, all normalized their spirometry parameters. However, most did not normalize their DLCO on follow up, raising concern for risk of developing chronic lung disease later in life.

With the intensification of global warming, rice production is facing new challenges. Field evidence indicates increased temperature during rice grain-filling lead to a further deterioration of grain quality. Clarifying the potential regulation mechanism of elevated temperature on rice development and quality formation will be contributed to develop suitable cultivation measures to better cope with climate warming in the future. In this study, open field warming and DIA mass spectrometry were conducted to explore the regulatory effects of high temperature on pathways related to grain development and material accumulation during the formation of rice quality. 840 differentially expressed proteins (fold change > 2, p-value < 0.05) were identified when exposed to high temperature. Among these, prolamin PPROL 14E, PSB28, granule-bound starch synthase 1 and 26.7 kDa heat shock protein were the most significantly regulated, and that ultimately affected the main substances accumulation of starch and protein in the kernel, and further degraded rice quality under high temperature. In addition, the results provided novel targets involved in regulating the metabolism of storage compounds under warming environment, and that will help us to better understand the regulation mechanism of global warming on the formation of rice quality.