Discover and publish cutting edge, open research.

Browse 6,934 multi-disciplinary research preprints


Most recent

Yeliz Kaya

and 2 more

Aim: The aim of this study was to determine menopausal symptoms, sleep levels, quality of life of women in the premenopausal, menopausal, and postmenopausal period, to increase their knowledge level with training to be provided, to reduce their menopausal symptoms, to improve quality of life and sleep quality, and to enable self-examination of breasts and vulva with training provided. Method: The research was conducted in a public hospital in Eskişehir. The study had a quasi-experimental design. The sample of the research consisted of 36 women aged between 40-65 years. These women were asked to complete the Sociodemographic Characteristics Determination Form, Menopause Rating Scale, Pittsburgh Sleep Quality Index, and Quality of Life Scale (SF-36) when they applied to menopause school. After the forms were completed, the participants were given training. Following training, the scales were re-completed and then women were enabled to perform self-examination of breasts (SEB) and self-examination of the vulva (SEV). The IBM SPSS Statistics 21.0 was used for the analysis. Results: The mean age of the women was 50.66±4.45 and that the mean menopause age was 47.60±3.45. The most frequently described symptom was fatigue (91.7%). It was seen that after the training, the MRS score of the women decreased from 16.83±8.87 to 13.66±8.36; the PSQI score decreased from 14.34±2.64 to 13.81±2.55; the mean Quality of Life (SF-36) scale score increased from 48.74±19.13 to 54.92±17.40. As a result of SEB and SEV performed by the women after the training, it was determined that 5.6% of the women had a breast deformity, that 8.3% had a palpable mass in the breast and that 13.9% detected a vaginal discharge in the vulva examination (p<0.05). Conclusion: It is easier to overcome this period with specific comprehensive training and women are enabled to cope with symptoms more effectively.

Natasha Picciani

and 5 more

Complex biological traits often originate by integrating previously separate parts, but the organismal functions of these precursors are challenging to infer. If we can understand the ancestral functions of these precursors, it could help explain how they persisted and how they facilitated the origins of complex traits. Animal eyes are some of the best studied complex traits, and they include many parts, such as opsin-based photoreceptor cells, pigment cells, and lens cells. Eye evolution is understood through conceptual models that argue these parts gradually came together to support increasingly sophisticated visual functions. Despite the well accepted logic of these conceptual models, explicit comparative studies to identify organismal functions of eye-precursors are lacking. Here, we investigate how precursors functioned before they became part of eyes in Cnidaria, a group formed by sea anemones, corals and jellyfish. Specifically, we test whether ancestral photoreceptor cells regulated the discharge of cnidocytes, the expensive single-use cells with various uses including prey capture, locomotion, and protection. Similar to a previous study of Hydra, we show an additional four distantly related cnidarian groups discharge significantly more cnidocytes when exposed to dim blue light compared to bright blue light. Our comparative analyses support the hypothesis that the cnidarian ancestor was capable of modulating cnidocyte discharge with light. Although eye-precursors might have had other functions like regulating timing of spawning, our findings are consistent with the hypothesis that photoreceptor cells which mediate cnidocyte discharge predated eyes, perhaps facilitating the prolific origination of eyes in Cnidaria.
Senna didymobotrya is invasive native flowering shrubs mainly grow in Africa. Climate change thought to facilitates the introduction and spread of invasive alien species. The present study aimed at examining the present and future invasion of S. didymobotrya under the changing climatic using species distribution modeling. The mean AUC and TSS value of the model was (95%) and (81%), respectively, which put the model under an excellent category. Our result showed under the current climatic conditions 18.11% of the continent is suitable for S. didymobotrya invasion. Eastern African countries are found the most suitable habitat for S. didymobotrya invasion followed by southern African countries. The total highly suitable area for the species is 3.4% and 3.17% in 2050s under RCP4.5 and RCP8.5, respectively. In the 2070s, the highly suitable area is predicted as 3.18 % and 2.73% in RCP4.5 and RCP8.5, respectively. An area with the category of low to moderate suitability under RCP 4.5 and RCP8.5 in the 2050s is projected as 17.4 % and 20.5 % and this area is increased in the 2070s to19.11% and 22.82 for the RCP 4.5 and RCP 8.5, respectively. The results of this study showed a substantial contraction in the high suitability areas, but a large increase in the low and moderately suitable habitat. Despite the contraction in highly suitable areas, countries which are found suitable in the present climatic condition remains suitable for S. didymobotrya establishment. Our ensemble predicted a significant increase in the vulnerability of habitat for invasion under the future climatic scenarios. Our study suggests the future biodiversity conservation strategy and policy direction should focus on the means and strategy of limiting the rate of expansion of invasion and distribution in different ecosystem types, hence reduce the expected harm in the ecosystem services.

Becky Lewis

and 7 more

Polyandry, when females mate with more than one male, is theorised to play an important role in successful colonisation of new habitats. In addition to possible benefits from sexual selection, even mild polyandry could facilitate colonisation by protecting against inbreeding and reducing the costs of mating with incompatible or infertile males. Here, we measure the importance of mild polyandry for population viability and reproductive fitness following experimental founder events into a higher temperature regime. Using colonisation experiments with the model beetle Tribolium castaneum, in which females can produce offspring for up to 140 days following a single mating, we founded more than 100 replicate populations using single females that had been given the opportunity to mate with either one or two males, and then tracked their subsequent population dynamics. Following population viability and fitness across ten generations, we found that extinction rates were significantly lower in populations founded by females given polyandrous opportunities to mate with two males (9%) compared to populations founded by monogamous females (34%). In addition, populations founded by females that had been provided with opportunities to store sperm from two different males showed double the median productivity following colonisation compared to monogamous-founded populations. Notably, we identified short-term and longer-term benefits to post-colonisation populations from double-mating, with results suggesting that polyandry acts to both protect against mating with incompatible males through the founder event, and reduce inbreeding depression as the colonisation proceeds for ten generations. Our results therefore show that even mild polyandry provides both reproductive and genetic benefits for colonising populations.
Aim. Repurposing strategies to address the COVID-19 pandemic have been accelerated. As both pregnant and pediatric patients are likely to be excluded from most planned investigations, the list of repurposed options and the available data on these drugs and vaccines provides a baseline risk assessment and identifies gaps for targeted investigation. Methods. Clinical trials have been searched and reviewed; twenty-three repurposed drugs and drug combinations and 9 candidate vaccines have been assessed regarding the availability of relevant data in pediatrics and pregnant women and to evaluate expected or unanticipated risk. Results. Thirteen of the repurposed drugs or drug combinations are indicated for use in pediatrics in some age category albeit for indications other than COVID-19; 10 of these are indicated for use in pregnant women. Even in cases where these drugs are indicated in the populations, source data from which safety and or dosing could be extrapolated for use in COVID-19 is sparse. Vaccine trials are ongoing and generally exclude pregnant women; only in a few instances have pediatric subgroups been planned for enrollment. Data from individual case studies and RWD may suggest that subpopulations of both pediatric patients and pregnant women may be more at risk, particularly those in an increased inflammatory state. Conclusion. In conjunction with more prospective collaboration, plans are evolving to ensure that we will be better prepared to address similar situations especially in pediatrics and pregnant women where experience is limited and actual practice relies heavily on leveraging data from other populations and indications.

Yong-sheng Zheng

and 9 more

Fig 1

Guillaume Lhermie

and 5 more

Peste des petits ruminants (PPR) is a contagious disease affecting small ruminants. It has been targeted by the global community for eradication within the next 10 years. Implementing eradication requires significant financial efforts, human resources, coordination among actors, and individual commitments. The objective of this study is to estimate the cost of PPR at household level, thereby providing economic information about the potential benefits for small ruminant keepers of PPR control and management strategies. Fifteen Sub-Saharan countries are included in this study, for which publicly available household level data assembled by FAO were used. We built a bioeconomic model to estimate the impact of PPR for a standardized theoretical area where each household raises an average herd comprising either 6 goats or 3 sheep and their offspring. We then used the outputs of the model to estimate the income loss due to PPR at household level. We constructed different income scenarios to account for the variability of small ruminant income in total annual income. The household income losses ranged from 0.6 to 44.8 percent of the total annual income. The percentages vary depending on the income scenario and on the gross annual economic impact of PPR on small ruminant production, which ranges from 25 to 80 percent based on the results of the bioeconomic model. Regardless of the income scenario, households in lower income quintiles are relatively more affected by PPR than households in upper quintiles. As expected, the more small ruminant production contributes to household income the greater the impact. We provide here estimates that may help, from a policy perspective, identifying the most relevant strategies and tailoring them at regional level to mitigate PPR impacts.
Final evali ct

Daniel Helfgott

and 8 more

AIM: To report on the clinical, laboratory and radiological findings of adolescents who presented during the SARS-CoV-2 surge with symptoms of COVID-19, did not test positive for the infection and were diagnosed with e-cigarette and vaping product use associated lung injury (EVALI). Methods: A retrospective review of 12 cases of EVALI admitted to the Bristol Meyers Squibb Children’s Hospital between February 2020 and June 2020 was conducted. Results: The ages of the patients ranged from 14 to 19 years. There were 6 males and 6 females. Three patients had a past history of anxiety, depression or other psychiatric/mental health disorder, nine had prolonged coagulation profile (PT,PTT and/or INR) and eleven had elevated inflammatory markers. Eleven needed respiratory support. All 12 were negative for SARS-CoV-2 PCR. Four were tested for IgG Antibodies and were negative. As these cases were admitted to rule out COVID infection, initial treatment included hydroxychloroquine. Steroids were started only after SARS-CoV-2 PCR was shown to be negative. Urine THC was positive in all cases. CXR and CT findings showed ground glass opacities. CONCLUSIONS: Clinical and radiological features are similar in both EVALI and SARS-CoV-2 infection. Inflammatory markers are elevated in both conditions. A detailed social and substance use history in patients presenting with ‘typical’ COVID pneumonia like illness is important. EVALI should be ruled in early to start the appropriate treatment. Given the ongoing pandemic, pediatricians and other health care providers need to be aware of other conditions that can masquerade as SARS-CoV-2.

Yuan Zhou

and 4 more

Background: Fibrosa layer stripping (FLS) technique is a new approach to remove calcified aortic valve. In this study, we aimed to assess the effectiveness of the FLS technique by comparing with the conventional technique in minimally invasive aortic valve replacement (MIAVR). Methods: A prospective, single-center, randomized controlled trial was conducted at Beijing Anzhen Hospital. 70 patients diagnosed with severe calcific aortic stenosis were randomly assigned to undergo FLS (n=35) or conventional (n=35) technique to debride calcified aortic valve. Preoperative profile, procedural parameters, and postoperative outcomes were analyzed. Results: No significant difference was observed in the preoperative profile between two groups. Compared with the conventional technique, the FLS technique had significantly higher indexed effective orifice area and lower mean gradient. Moreover, FLS technique was associated with significantly reduced aortic cross-clamp time (41[38-44] vs 56[51-60] min, p<0.001), cardiopulmonary bypass (CPB) time (63[56-69] vs 81[75-84] min, p<0.001) and operative time (148[141-156] vs 173[169-180] min, p<0.001). Lastly, the length of intensive care unit stay (1.2±0.4 vs 1.5±0.8 days, p=0.041) and hospital stay (5.3±0.6 vs 6.0±1.4 days, p=0.020) was significantly reduced in the FLS group compared with those in the conventional group. Conclusions: FLS technique is effective in removing calcified tissue during MIAVR and is associated with shorter cross-clamp time and CPB time, and better hemodynamic performance than conventional technique.

Mehmet Degirmenci

and 1 more

Objective: We aimed to investigate the effects of tobacco in the diseases that may require surgical treatment and thus contribute to the prevention of the development and treatment of lung diseases Background: Tobacco can make respiratory diseases more complicated by affecting their respiratory functions in a short or long time and can increase mortality and morbidity related to these diseases. Method: We retrospectively analyzed 754 patients aged 18 - 95. Patients included in the study were divided into two groups as tobacco users and non-users. We examined patients in each group in terms of age, gender, diagnosis of the disease, complications developing during and after treatment, and length of hospital stay. Results: The patients consisted of 536 (71.1%) males and 218 (28.9%) females. The average age of patients was 46.91 ± 22.07 (Min: 18 Max: 95). 56.1% of all patients and 73.3% of male patients used tobacco, and tobacco use was more common among men (X2 = 223.216, p < 0.001). Tobacco use was significantly higher in patients under 35 years of age (X2 = 45.342, p < 0.001). The average length of hospital stay was 9.41 ± 7.26 days for tobacco users and 8.15 ± 6.47 days for non-tobacco users (Mann-Whitney U test = 61949.0, p<0.007). Complications occurred in 96 of 754 patients, included in the study 76 (79.2%) of whom used tobacco, and 20 (20.8%) did not use tobacco (X2 = 23.765, p<0.001). Spontaneous pneumothorax and lung cancer have been observed significantly more in tobacco users (respectively X2 = 96.196, p < 0.001; X2 = 4.735, p = 0.030). Conclusion: We recommend supporting tobacco control programs to prevent the effect of tobacco use on pulmonary surgical diseases, and the development of pulmonary complications. Keywords: tobacco use, postoperative pulmonary complication, thoracic surgery, smoking, surgical diseases

Dian Chen

and 7 more

Background: Several predictors for the severity of coronavirus disease 2019 (COVID-19) have been reported. However, chronic airway inflammation characterized by accumulated lymphocytes or eosinophils may affect the pathogenesis of COVID-19. Methods: In this retrospective cohort study, we reviewed medical records of all laboratory confirmed COVID-19 patients with chronic bronchitis, chronic obstructive pulmonary disease (COPD) and asthma admitted in Sino-French New City Branch of Tongji Hospital, a large regional hospital in Wuhan, China, from January 26th to April 3rd. The Tongji Hospital ethics committee approved this study. Results: There were 59 patients with underlying chronic airway inflammation including chronic bronchitis, COPD and asthma. When compared with non-severe patients, severe patients were more likely to have decreased lymphocyte counts (0.6vs.1.1×10⁹/L, p<0.001), eosinopenia (<0.02×10⁹/L, 73%vs.24%, p<0.001), increased lactate dehydrogenase (LDH) (471.0vs.230.0 U/L, p<0.001) and elevated IL-6 level (47.4vs.5.7 pg/ml, p=0.002) on admission. Eosinopenia and elevated LDH were significantly associated with disease severity in both univariate and multivariate regression models included the above variables. Eosinopenia was also an independent risk factor for mortality of this cohort in a multivariate model included the above variables. Moreover, eosinophil counts and LDH levels tended to return to normal range over time in both groups after treatment and severe patients recovered slower than non-severe patients, especially eosinophil counts. Conclusions: Eosinopenia and elevated LDH are potential predictors of disease severity in COVID-19 patients with underlying chronic airway diseases. Theses predictors may help clinicians identify the severe COVID-19 patients with chronic bronchitis, COPD and asthma.

Su-Jeong Kim

and 5 more

BACKGROUND: The coronavirus disease-2019 (COVID-19) is still rapidly spreading worldwide, and remains a global health crisis. We investigated the impact of asthma on the prevalence and outcomes of COVID-19 and identify the risk factors for delayed viral clearance. METHODS: Adult patients with COVID-19 admitted to 10 hospitals in Daegu were retrospectively registered, and their clinical information was collected. Delayed viral clearance was divided into two groups based on 30 days. RESULTS: A total of 2,200 patents were evaluated, and the prevalence of asthma in COVID-19 was 3.2%. Compared with Korea nationwide survey data, there were no differences in asthma prevalence. In the univariate analysis, the risk of death (13.6% vs 6.4%, P = 0.021) and high flow oxygen therapy (18.2% vs 10.5%, P = 0,048) was increased in asthma patients, with a stronger tendency among elderly, women, and overweight patients. However, in a multivariate analysis using the logistic regression model, any clinical outcomes according to asthma was not significant. The risk factors for delayed viral clearance were older age >65 years (Odds ratio [95% confidence interval] 2.002 [1.292–3101]), dementia (3.123 [1.833–5.321]), skin rash (15.943 [1.613–157.535]), and anemia (2.156 [1.061–2.377]), whereas headache (0.673 [0.485–0.932]) lowered the risk. CONCLUSIONS: There may be a difference depending on phenotypes, but asthma prevalence was not significantly different in patients with COVID-19, and asthma did not affect outcomes of COVID-19. Older age, dementia, headache, skin rash, and anemia were independently associated with delayed viral clearance.
Figure 1

Phornpimon Tipthara

and 9 more

BACKGROUND AND PURPOSE Mass drug administration of ivermectin has been proposed as a possible malaria elimination tool. Ivermectin exhibits a mosquito-lethal effect well beyond its biological half-life, suggesting the presence of active slowly eliminated metabolites. EXPERIMENTAL APPROACH Human liver microsomes, primary human hepatocytes, and whole blood from healthy volunteers given oral ivermectin were used to identify ivermectin metabolites by ultra-high performance liquid chromatography coupled with high resolution mass spectrometry. The molecular structures of metabolites were determined by mass spectrometry and verified by nuclear magnetic resonance. Pure cytochrome P450 enzyme isoforms were used to elucidate the metabolic pathways. KEY RESULTS Thirteen different metabolites (M1-M13) were identified after incubation of ivermectin with human liver microsomes. Three (M1, M3, and M6) were the dominant metabolites found in microsomes, hepatocytes, and blood from volunteers after oral ivermectin administration. The chemical structure defined by LC-MS/MS and NMR indicated that M1 is 3″-O-demethyl ivermectin, M3 is 4-hydroxymethyl ivermectin, and M6 is 3″-O-demethyl, 4-hydroxymethyl ivermectin. Metabolic pathway evaluations with characterized cytochrome P450 enzymes showed that M1 was produced by CYP3A4 and CYP3A5, and that M3 and M6 were produced by CYP3A4. CONCLUSIONS AND IMPLICATIONS Demethylated and hydroxylated ivermectin are the main human metabolites in vivo. Further study to characterize their pharmacokinetic properties and mosquito-lethal activity is now needed.

Browse more recent preprints

Recently published in scholarly journals

Rand Ibrahim

and 1 more

Sudden Cardiac Death (SCD) remains a global threat.1The most common causes of SCD are ischemic heart diseases and structural cardiomyopathies in the elderly. Additional causes can be arrhythmogenic, respiratory, metabolic, or even toxigenic.2,3,4 Despite the novel diagnostic tools and our deeper understanding of pathologies and genetic associations, there remains a subset of patients for whom a trigger is not identifiable. When associated with a pattern of Ventricular Fibrillation, the diagnosis of exclusion is deemed Idiopathic Ventricular Fibrillation (IVF).2,5 IVF accounts for 5% of all SCDs6 – and up to 23% in the young male subgroup5 – and has a high range of recurrence rates (11-45%).7,8,9 There are still knowledge gaps in the initial assessment, follow-up approach, risk stratification and subsequent management for IVF.1,10,11 While subsets of IVF presentations have been better characterized into channelopathies, such as Brugada’s syndrome (BrS), Long QT Syndrome (LQTS), Early Repolarization Syndrome (ERS), Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), much remains to be discovered.12,13 Implantable Cardioverter Device (ICD) placement as secondary prevention for IVF is the standard of care. This is warranted in the setting of high recurrence rates of arrhythmias (11-43%). Multiple studies have shown potential complications from ICDs and a significant number of cases experiencing inappropriate shock after ICD placement.14In their article, Stampe et al. aim to further understand clinical presentation and assessment, and risk factors for recurrent ventricular arrhythmias in IVF patients. Using a single-centered retrospective study, they followed a total of 84 Danish patients who were initially diagnosed with IVF and received a secondary ICD placement between December 2007 and June 2019. Median follow-up time was 5.2 years (ICR=2-7.6). To ensure detection of many possible underlying etiologies ranging from structural, ischemic, arrhythmogenic, metabolic, or toxicologic, the researchers found that a wide array of diagnostic tools were necessary: standard electrocardiograms (ECGs), high-precordial leads ECGs, standing ECGs, Holter monitoring, sodium-channel blocker provocation tests, exercise stress tests, echocardiograms, cardiac magnetic resonance imaging, coronary angiograms, cardiac computed tomography, electrophysiological studies, histological assessment, blood tests, toxicology screens, and genetic analysis.The study by Stampe et al. highlights the importance of thorough and continuous follow-up with rigorous evaluation: Three (3.6%) patients initially diagnosed with IVF were later found to have underlying cardiac abnormalities (LQTS and Dilated Cardiomyopathy) that explained their SCA. Like other studies, the burden of arrhythmia was found to be high, but unlike reported data, the overall prognosis of IVF was good. Despite the initial pattern of ventricular fibrillation in those who experienced appropriate ICD placement (29.6%), ventricular tachycardia and ventricular fibrillation had a comparable predominance. As for patients with inappropriate ICD placements, atrial fibrillation was a commonly identified pathological rhythm (16.7%). Recurrent cardiac arrest at presentation (19.8%) was a risk factor for appropriate ICD therapy (HR=2.63, CI=1.08-6.40, p=0.033). However, in contrast to previous studies, early repolarization detected on baseline ECG (12.5%), was not found to be a risk factor (p=0.842).The study by Stampe et al. has few limitations. First, the study design, a retrospective cohort, precluded standardized follow-up frequencies and diagnostic testing. Second, while the study was included many of the cofounders tested in previous studies (baseline characteristics, baseline ECG patterns, comorbidities), medication use was not included. Third, the follow-up period may have been insufficient to detect effect from some of the confounding factors. Finally, the sample size was small and it was from a single center.There are several strengths of the Stampe et al. study. Firstly, the wide range of diagnostic tests used at index presentation and during the follow-up period ensured meticulous detection of most underlying etiologies. Secondly, appropriate and well-defined inclusion and exclusion criteria were used. Thirdly, funding by independent parties ensured no influence on study design, result evaluation, and interpretation. Finally, the study has succeeded in improving our understanding of IVF. Future studies should include though a larger population size and a more diverse population.References:1.AlJaroudi WA, Refaat MM, Habib RH, Al-Shaar L, Singh M, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.2. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: executive summary. J Am Coll Cardiol 2018;72:e91–e220.3. Refaat MM, Hotait M, London B: Genetics of Sudden Cardiac Death. Curr Cardiol Rep Jul 2015; 17(7): 6064. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013;10:1932–1963.5. Priori SG, Blomström-Lundqvist C, Mazzanti A, et al. ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015;36(41):2793-2867.6. Zipes DP, Wellens HJ. Sudden cardiac death. Circulation. 1998;98:2334–2351.7. Ozaydin M, Moazzami K, Kalantarian S, Lee H, Mansour M, Ruskin JN. Long-term outcome of patients with idiopathic ventricular fibrillation: a meta-analysis. J Cardiovasc Electrophysiol 2015;26:1095–1104.8. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry. Circ Arrhythm Electrophysiol 2016;9:e003619.9. Siebermair J, Sinner MF, Beckmann BM, Laubender RP, Martens E, Sattler S, et al.Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years. Europace 2016;18:718-25.10. Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.11. Gray B, Ackerman MJ, Semsarian C, Behr ER. Evaluation after sudden death in the young: a global approach. Circ Arrhythm Electrophysiol 2019;12: e007453.12. Herman AR, Cheung C, Gerull B, Simpson CS, Birnie DH, Klein GJ, et al. Response to Letter Regarding Article, Outcome of apparently unexplained cardiac arrest: results from investigation and follow-up of the prospective cardiac arrest survivors with preserved ejection fraction registry”. Circ Arrhythm Electrophysiol 2016;9:e004012.13. Chen Q, Kirsch GE, Zhang D, Brugada R, Brugada J, Brugada P, Potenza D, et al. Genetic basis and molecular mechanism for idiopathic ventricular fibrillation. Nature 1998;392:293–296.14. Baranchuk A, Refaat M, Patton KK, Chung M, Krishnan K, et al. What Should You Know About Cybersecurity For Cardiac Implantable Electronic Devices? ACC EP Council Perspective. J Am Coll Cardiol Mar 2018; 71(11):1284-1288.

Zengguo Cao

and 17 more

Ebolavirus (EBOV) is responsible for several EBOV disease (EVD) outbreaks in Africa, with a fatality rate of up to 90%. During 2014-2016, An epidemic of EVD spread throughout Sierra Leone, Guinea and Liberia, and killed over 11,000 people. EBOV began to circulate again in the Democratic Republic of Congo in 2018. Due to the need for a BSL-4 facility to manipulate this virus, the development and improvement of specific therapeutics has been hindered. As a result, it is imperative to perform reliable research on EBOV under lowered BSL restrictions. In this study, we developed a safe neutralization assay based on pseudotyped EBOV, which incorporates the glycoprotein of the 2014 EBOV epidemic strain into a lentivirus vector. Our results demonstrated that the tropism of pseudotyped EBOV was similar to that of authentic EBOV, but with only one infection cycle. And neutralizing activity of both authentic EBOV and pseudotyped EBOV were compared in neutralization assay using three different samples of antibody-based reagents against EBOV, similar results were obtained. In addition, an indirect ELISA was performed to show the relationship between IgG and neutralizing antibody against EBOV detected by our pseudotyped EBOV-based neutralization assay. As expected, the neutralizing antibody titers varied with the IgG titers detected by indirect ELISA, and a correlation between the results of the two assays was identified. By comparison with two different assays, the reliability of the results detected by the pseudotyped EBOV-based neutralization assay was confirmed. Collectively, in the absence of BSL-4 restrictions, pseudotyped EBOV production and neutralizing activity evaluation can be performed safely and in a manner that is neither labor- nor time-consuming, providing a simple and safe method for EBOV-neutralizing antibody detection and the assessment of immunogenicity of EBOV vaccines. All these remarkable advantages of the newly established assay highlight its potential to further application in assessment of immunogenicity of EBOV vaccine candidates.

Bachir Lakkis

and 1 more

Long QT syndrome (LQTS) is characterized by prolongation of the QT interval on the electrocardiogram (ECG). Clinically, LQTS is associated with the development of Torsades de Pointes (TdP), a well-defined polymorphic ventricular tachycardia and the development of sudden cardiac death (1). The most common type is the acquired form caused mainly by drugs, it is also known as the drug induced LQTS (diLQTS) (2-5). The diLQTS is caused by certain families of drugs which can markedly prolong the QT interval on the ECG most notably antiarrhythmic drugs (class IA, class III), anti-histamines, antipsychotics, antidepressants, antibiotics, antimalarial, and antifungals (2-5). Some of these agents including the antimalarial drug hydroxycholoquine and the antibiotic azithromycin which are being used in some countries as therapies for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)(6,7). However, these drugs have been implicated in causing prolongation of the QT interval on the ECG (2-5).There is a solution for monitoring this large number of patients which consists of using mobile ECG devices instead of using the standard 12-lead ECG owing to the difficulty of using the 12-lead ECG due to its medical cost and increased risk of transmitting infection. These mobile ECG devices have been shown to be effective in interpreting the QT interval in patients who are using QT interval prolonging drugs (8, 9). However, the ECG mobile devices have been associated with decreased accuracy to interpret the QT interval at high heart rates (9). On the other hand, some of them have been linked with no accuracy to interpret the QT interval (10). This can put some patients at risk of TdP and sudden cardiac death.In this current issue of the Journal of Cardiovascular electrophysiology, Krisai P et al. reported that the limb leads underestimated the occurrence of diLQTS and subsequent TdP compared to the chest leads in the ECG device, this occurred in particular with the usage of mobile standard ECG devices which use limb leads only. To illuminate these findings, the authors have studied the ECGs of 84 patients who have met the requirements for this study, which are diLQTS and subsequent TdP. Furthermore, the patients in this study were also taking a QT interval prolonging drug. Krisai P et al. additionally reported the morphology of the T-wave in every ECG and classified them into flat, broad, notched, late peaked, biphasic and inverted. The authors showed that in 11.9% of these patients the ECG was non reliable in diagnosing diLQTS and subsequent Tdp using only limb leads due to T-wave flattening in these leads, in contrast to chest leads where the non- interpretability of the QT interval was never attributable to the T-wave morphology but to other causes. The authors further examined the QT interval duration in limb leads and chest leads and found that the QT interval in limb leads was shorter compared to that of the chest leads, but reported a high variability in these differences. Therefore, it should be taken into account when screening patients with diLQTS using only mobile ECG devices and these patients should be screened using both limb leads and chest leads. Moreover, the authors have highlighted the limitations of using ECG mobile devices as limb leads to interpret the QT interval especially in high heart rates (when Bazett’s equation overcorrects the QTc and overestimates the prevalence of the QT interval) and have advocated the usage of ECG mobile devices as chest leads instead of limb leads due to their superior ability to interpret the QT interval.The authors should be praised for their efforts in illustrating the difference in the QT interval interpretability between the chest leads and the limb leads in patients with diLQTS. The authors also pointed out the limitation of using mobile ECG devices as limb leads for the diagnosis of diLQTS and recommended their usage as chest leads by applying their leads onto the chest due to their better diagnostic accuracy for detecting the diLQTS. The study results are very relevant, it further expanded the contemporary knowledge about the limitation of the QT interval interpretability using ECG mobile device only (11). Future investigation is needed to elucidate the difference in chest and limb leads interpretability of the QT interval and to assess the ability of the mobile ECG devices to interpret the QT interval.ReferencesRefaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification. Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.Kannankeril P, Roden D, Darbar D. Drug-Induced Long QT Syndrome. Pharmacological Reviews. 2010;62(4):760-781.Nachimuthu S, Assar M, Schussler J. Drug-induced QT interval prolongation: mechanisms and clinical management. Therapeutic Advances in Drug Safety. 2012;3(5):241-253.Jankelson L, Karam G, Becker M, Chinitz L, Tsai M. QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review. Heart Rhythm. 2020 ; S1547-5271(20)30431-8.Li M, Ramos LG. Drug-Induced QT Prolongation And Torsades de Pointes. P T . 2017;42(7):473-477.Singh A, Singh A, Shaikh A, Singh R, Misra A. Chloroquine and hydroxychloroquine in the treatment of COVID-19 with or without diabetes: A systematic search and a narrative review with a special reference to India and other developing countries. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(3):241-246.Hashem A, Alghamdi B, Algaissi A, Alshehri F, Bukhari A, Alfaleh M et al. Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review. Travel Medicine and Infectious Disease. 2020; 35:101735.Chung E, Guise K. QTC intervals can be assessed with the AliveCor heart monitor in patients on dofetilide for atrial fibrillation. J Electrocardiol. 2015;48(1):8-9.Garabelli P, Stavrakis S, Albert M et al. Comparison of QT Interval Readings in Normal Sinus Rhythm Between a Smartphone Heart Monitor and a 12-Lead ECG for Healthy Volunteers and Inpatients Receiving Sotalol or Dofetilide. Journal Cardiovasc Electrophysiol. 2016;27(7):827-832.Bekker C, Noordergraaf F, Teerenstra S, Pop G, Bemt B. Diagnostic accuracy of a single‐lead portable ECG device for measuring QTc prolongation. Annals Noninvasive Electrocardiol. 2019;25(1): e12683.Malone D, Gallo T, Beck J, Clark D. Feasibility of measuring QT intervals with a portable device. American Journal of Health-System Pharmacy. 2017;74(22):1850-1851.
Figure 1

Volkan Sen

and 9 more

Objectives: There is no standardized and up-to-date education model for urology residents in our country. We aimed to describe our National E learning education model for urology residents. Methodology: The ERTP working group; consisting of urologists was established by Society of Urological Surgery to create E-learning model and curriculum at April 2018. Learning objectives were set up in order to determine and standardize the contents of the presentations. In accordance with the Bloom Taxonomy, 834 learning objectives were created for a total of 90 lectures (18 lectures for each PGY year). Totally 90 videos were shoot by specialized instructors and webcasts were prepared. Webcasts were posted at, which is the web library of Society of Urological Surgery. Satisfaction of residents and instructors was evaluated with feedbacks. An assessment of knowledge was measured with multiple-choice exam. Results: A total of 43 centers and 250 urology residents were included in ERTP during the academic year 2018/2019. There were 93/38/43/34/25 urology residents at 1st/2nd/3rd/4th and 5th year of residency, respectively. Majority of the residents (99.1%) completed the ERTP. The overall satisfaction rate of residents and instructors were 4,29 and 4,67(min:1 so bad, max:5 so good). An assessment exam was performed to urology residents at the end of the ERTP and the mean score was calculated as 57.99 points (min:20, max:82). Conclusion: Due to the Covid-19 pandemic, most of the educational programs had to move online platforms. We used this reliable and easily accessible e-learning platform for standardization of training in urology on national basis. We aim to share this model with international residency training programs.

Mohammad Ramadan

and 1 more

Atrial fibrillation (AF) is the most common cardiac arrhythmia and often occurs with heart failure (HF) [1]. AF prevalence increases with increasing severity of HF: for instance its prevalence ranges from 5 percent in patients with New York Heart Association (NYHA) functional class I HF to 40 percent in patients with NYHA class IV HF [2]. Its presence with HF plays a significant prognostic role and increases morbidity and mortality. Heart Failure with reduced ejection fraction (HFrEF) is associated with cardiac arrhythmias [3]. HFrEF is also one of the indications for Cardiac resynchronization therapy (CRT) placement [4]. Therefore, many patients undergoing CRT implantation will concomitantly have HF and AF. As the benefit from CRT in HF patients has been established, the data on patients with both HF and AF is limited, because patients with atrial arrhythmias were excluded from most of the major CRT trials, such as CARE-HF and COMPANION [5]. However, a number of observational studies and small randomized clinical trials suggest a benefit from CRT in AF and HF patients such as a CRT-mediated ejection fraction (EF) increase [6, 7]. Other studies showed a high non-response rate in patients with AF as compared to those in sinus rhythm (SR) [8]. Thus, it is important to determine whether CRT has a beneficial role in these patients to decide on adding an atrial lead at the time of CRT implantation especially in patients with longstanding-persistent AF.In their published study, Ziegelhoeffer et al. investigated the outcomes of CRT placement with an atrial lead in patients with HF and AF. This was done by conducting a retrospective analysis of all patients with AF who received CRT for HF at the Kerckhoff Heart Center since June 2004 and were observed until July 2018- completing a 5-year follow-up. The authors identified 328 patients and divided them into 3 subgroups: paroxysmal (px) AF, persistent (ps) AF, and longstanding-persistent (lp) AF, with all patients receiving the same standard operative management. During the observation period, the authors analyzed the rhythm course of the patients, cardiac parameters (NYHA class, MR, LVEF, left atrial diameter) and performed a subgroup analysis for patients who received an atrial lead. The study showed that all groups had a high rate of sinus rate (SR) conversion and rhythm maintenance at 1 and 5 years. Specifically, the patients who received an atrial lead among the lp AF group were shown to have a stable EF, less pronounced  left ventricular end-systolic diameter (LVESD) and  left ventricular end diastolic diameter (LVEDD) and lower mitral regurgitation (MR) rates at one year follow-up as compared to the group without atrial lead placement. Moreover, the results of the lp group were similar to the ps-AF group, although the latter had a lower number of participants (n=4) without initial implantation of the atrial lead. The authors attributed the improvement in cardiac function and SR conversion to CRT and the implantation of an additional atrial lead.Although some studies showed that CRT therapy reduced secondary MR in HF [9, 10], this study additionally suggests that CRT with an atrial lead was associated with improved myocardial function and improvement of interventricular conduction delay triggering cardiac remodeling in patients with HF and AF. Although the results showed better cardiac function in the subgroup analysis of the patients with an additional atrial lead, these results were reported as percentages with no level of significance specified, hence statistical significance of the difference in the described parameters (such as LVESD, LVEDD) could not be determined. Further investigation via prospective studies is needed with larger sample size in the future to further support the results of the study especially that it was done in a single center and had a relatively small sample size.References:1. Chung MK, Refaat M, Shen WK, et al. Atrial Fibrillation: JACC Council Perspectives. J Am Coll Cardiol. Apr 2020; 75 (14): 1689-1713.2. Maisel, W.H. and L.W. Stevenson, Atrial fibrillation in heart failure: epidemiology, pathophysiology, and rationale for therapy. Am J Cardiol, 2003. 91 (6a): p. 2d-8d.3. AlJaroudi WA, Refaat MM, Habib RH, et al. Effect of Angiotensin Converting Enzyme Inhibitors and Receptor Blockers on Appropriate Implantable Cardiac Defibrillator Shock: Insights from the GRADE Multicenter Registry. Am J Cardiol Apr 2015; 115 (7): 115(7):924-31.4. Yancy, C.W., et al., 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol, 2013. 62 (16): p. e147-239.5. Cleland, J.G., et al., The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med, 2005.352 (15): p. 1539-49.6. Leclercq, C., et al., Comparative effects of permanent biventricular and right-univentricular pacing in heart failure patients with chronic atrial fibrillation. Eur Heart J, 2002. 23 (22): p. 1780-7.7. Upadhyay, G.A., et al., Cardiac resynchronization in patients with atrial fibrillation: a meta-analysis of prospective cohort studies. J Am Coll Cardiol, 2008. 52 (15): p. 1239-46.8. Wilton, S.B., et al., Outcomes of cardiac resynchronization therapy in patients with versus those without atrial fibrillation: a systematic review and meta-analysis. Heart Rhythm, 2011. 8 (7): p. 1088-94.9. van Bommel, R.J., et al., Cardiac resynchronization therapy as a therapeutic option in patients with moderate-severe functional mitral regurgitation and high operative risk. Circulation, 2011.124 (8): p. 912-9.10. Breithardt, O.A., et al., Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure. J Am Coll Cardiol, 2003. 41 (5): p. 765-70.

Mohamad El Moheb

and 1 more

Idiopathic ventricular arrhythmias (VA) is defined as premature ventricular complexes (PVCs) or ventricular tachycardias (VT) that occur in the absence of structural heart disease. Endocardial radiofrequency (RF) ablation is often curative for idiopathic VA. The success of the procedure depends on the ability to localize the abnormal foci accurately. These arrhythmias typical originate from the right ventricular outflow tract (RVOT), specifically from the superior septal aspect, but can also originate from the left ventricular outflow tract (LVOT) and the coronary cusps.1 The QRS electrocardiogram (ECG) characteristics have been helpful in patients with VAs, patient with accessory pathways and patients who have pacemakers.2 VAs originating from the RVOT have typical ECG findings with a left bundle branch block (LBBB) morphology and an inferior axis.3In the current issue of the Journal of Cardiovascular Electrophysiology, Hisazaki et al. describe five patients with idiopathic VA suggestive of RVOT origin and who required ablation in the left-sided outflow tract (OT) in addition to the initial ablation in the RVOT for cure to be achieved. Patients exhibited monomorphic, LBBB QRS pattern with an inferior axis on ECG, consistent with the morphology of VAs originating from the RVOT. Interestingly, all patients had a common distinct ECG pattern: qs or rs (r ≤ 5 mm) pattern in lead I, Q wave ratio[aVL/aVR]>1, and dominant S-waves in leads V1 and V2. Mapping of the right ventricle demonstrated early local activation time during the VA in the posterior portion of the RVOT, matching the QRS morphology obtained during pacemapping. Despite RF energy delivery to the RV, the VAs recurred shortly after ablation in four patients and had no effect at all in one patient. A change in the QRS morphology was noted on the ECG that had never been observed before the procedure. The new patterns were suggestive of left-sided OT origin: the second VAs exhibited an increase in the Q wave ratio [aVL/aVR] and R wave amplitude in lead V1, decrease in the S wave amplitude in lead V1, and a counterclockwise rotation of the precordial R-wave transition. Early activation of the second VA could not be found in the RVOT, and the earliest activation time after mapping the LV was found to be relatively late. Real-time intracardiac echocardiography and 3D mapping systems were used to determine the location immediately contralateral to the initial ablation site in the RVOT. Energy was then delivered to that site which successfully eliminated the second VA. The authors postulated that the second VAs shared the same origins as the first VAs, and the change in QRS morphology is likely attributed to a change in the exit point or in the pathway from the origin to the exit point. The authors further explained that the VAs originated from an intramural area of the superior basal LV surrounded by the RVOT, LVOT and the transitional zone from the great cardiac vein to the anterior interventricular vein (GCV-AIV).A limitation of this study is that GCV-AIV ablation was not attempted; however, the authors’ approach is safer and was successful in eliminating VA. Another limitation is that left-sided OT mapping was not initially performed. Nevertheless, given the ECG characteristics, local activation time, and mapping, it was appropriate to attempt a RVOT site ablation.Overall, the authors should be commended for their effort to describe in detail patients with idiopathic VAs that required ablation in the left-sided OT following ablation in the RVOT. Although change in QRS morphology after ablation has been previously described, the authors were the first to describe the ECG patterns of these patients.4–7 The results of this study have important clinical implications. First, the authors have demonstrated the importance of anatomical approach from the left-sided OT for cure to be achieved. Second, insight into the location of the origin of the VA may be helpful to physicians managing patients with VAs from the RVOT. Finally, continuous monitoring of the ECG during ablation for a change in QRS morphology should be considered to identify patients who will require further ablation. We have summarized in Table 1 important ECG characteristics indicative VA of specific origins, based on the findings of this study and previous studies in the literature.3,8–15
Pulmonary Vein Isolation (PVI) remains the cornerstone for catheter ablation for atrial fibrillation (AF). Achieving durable PVI safely with Radiofrequency Catheter Ablation (RFCA) has proven challenging until recently, even with the use of Contact Force (CF) sensing catheters and electroanatomical mapping1. Ablation success rates improve markedly, including in persistent AF, when permanent PVI can be achieved1,2, which only underscores the critical role of the Pulmonary Veins (PV) in AF arrhythmogenesis.Historically, the only way to assess PVI durability has been through invasive electrophysiology study, with all its associated risk, inconvenience, and costs. This price appears particularly galling to pay if the PVs are found to be isolated at repeat study, as is now becoming increasingly common3. Multiple randomised studies have failed to show additional benefit from ablating extra-PV structures4,5, and the best outcomes following repeat AF ablation procedures are restricted to those where PV reconnection is identified and treated6. As such, there remains a pressing need for a non-invasive tool that can accurately assess PVI durability, and ideally, the size and location of residual gaps. As Magnetic Resonance Imaging (MRI) has increasingly been shown capable of delineating atrial scar, there is much anticipation that it may serve this important purpose7.RFCA and Cryoballoon ablation (CBA) are by far the most common modalities used for PVI, and there is remarkable equivalence in their clinical results8. However, the handling of the two technologies in the catheter laboratory is very different, and ultrahigh density mapping has shown important differences in the number and location of chronic gaps between the two9. The use of MRI in characterizing these differences has not been well described so far.In this issue of the journal, Kurose and colleagues present a small but elegant study10, in which 30 consecutive patients who underwent PVI (18 with CBA, 12 with RFCA) were assessed by LGE-MRI two months later, where lesion width and visual gap(s) around each vein were assessed. The RF applications were delivered using a CF sensing catheter, with a target lesion size index (LSI) of 5, and an inter-lesion distance of <6mm. They found that the mean lesion width on MRI was significantly wider in the CBA group (8.1±2.2 mm) as compared to the RFCA group (6.3±2.2 mm), p=0.032. However, there were more visual gaps seen in the CBA group, especially in the bottom segments of the two inferior veins. In the RFCA group, gaps were seen most often seen in the left posterior segments where the target LSI value could not be achieved because of esopheageal temperature rise. Furthermore, the number of gaps visualised on MRI was linked to freedom from AF at 12 months; receiver operating characteristic curve analysis suggested a cut off value of less than 5 visual gaps per patient as being predictive of a good outcome.The authors deserve to be congratulated for their study, which builds on their previous work where LGE-MRI was used to compare chronic lesions between CBA and RFCA with non-CF sensing catheters11. It is notable that whilst the lesion width in their previous study was also significantly greater in the CBA group than the RFCA group, the mean number of gaps in the RFCA group was higher. This suggests that the modern technique of delivering LSI-guided contiguous RFCA lesions has resulted in a material improvement in PVI durability, something that is borne out in clinical studies too3.Some limitations of the work should be mentioned. Patients were not randomised to RFCA or CBA; rather, patients undergoing CBA were pre-selected with those with left common PV or large PVs excluded. The ablation technique used for CBA was unusual in that the use of RFCA was allowed if PVI could not be achieved after a single 3-minute freeze. This low bar for defining CBA failure led to as many as 3 patients out of 25 being excluded from the study. Many readers will feel that the mean procedural times of 129 minutes and fluoroscopy times of 39 minutes for CBA are much longer than what is the norm today. They may also find the RF powers used in this study unusual; only 30W was used on the anterior wall, and 20-25W on the posterior wall, which was reduced even further if esophageal temperature rise was observed. The field is moving towards using higher power short duration (HPSD) RF applications, and as HPSD lesions have been shown to be wider12, it is possible that the gaps on the posterior wall identified in this study may not have been present had HPSD applications been used. Finally, the definition of visual gap on MRI used in this study, a non-LGE site larger than 4 mm, almost certainly overestimated the number of true gaps. For instance, the authors observed at least one visual gap in each of the 16 segments around the PVs in more than 10% CB patients; this is at odds with data obtained with ultrahigh density mapping9, and also with the good clinical outcomes reported here. Future research should look at correlating these MRI-visualised gaps with actual gaps seen on repeat electrophysiological study, so that the clinical significance of these can be better defined.What can we take away from this study? Firstly, the use of MRI to assess post-ablation scar is now a reality in many labs, allowing assessment of PVI durability to help decide whether or not to offer a repeat procedure to a patient with AF recurrence. Secondly, the evolution of the RFCA technique to include target lesion indices and inter-lesion distance has made RFCA at least as effective as CBA in achieving durable PVI. Finally, this is an area ripe for further research, and we look forward to similarly valuable contributions from Kurose and colleagues in the future.
Figure 1

Chan Sol Park

and 7 more

Background and Purpose: After spinal cord injury (SCI), blood-spinal cord barrier (BSCB) disruption results in secondary injury including apoptotic cell death of neurons and oligodendrocytes, thereby leads to permanent neurological deficits. Recently, we reported that the histone H3K27me3 demethylase Jmjd3 plays a role in regulating BSCB integrity after SCI. Here, we investigated whether gallic acid (GA), a natural phenolic compound that is known to be anti-inflammatory, regulates Jmjd3 expression and activation, thereby attenuates BSCB disruption following the inflammatory response and improves functional recovery after SCI. Experimental Approach: Rats were contused at T9 and treated with GA (50 mg/kg) via intraperitoneal injection immediately, 6 h and 12 h after SCI, and further treated for 7 d with the same dose once a day. To elucidate the underlying mechanism, we evaluated Jmjd3 activity and expression, and assessed BSCB permeability by Evans blue assay after SCI. Key Results: GA significantly inhibited Jmjd3 expression and activation after injury both in vitro and in vivo. GA also attenuated the expression and activation of matrix metalloprotease-9, which is well known to disrupt the BSCB after SCI. Consistent with these findings, GA attenuated BSCB disruption and reduced the infiltration of neutrophils and macrophages compared with the vehicle control. Finally, GA significantly alleviated apoptotic cell death of neurons and oligodendrocytes and improved behavior functions. Conclusions and Implications: Based on these data, we propose that GA can exert a neuroprotective effect by inhibiting Jmjd3 activity and expression followed the downregulation of matrix metalloprotease-9, eventually attenuating BSCB disruption after SCI.

Jorge Casanova

and 4 more

ABSTRACT Background: COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11st, 2020. Responses to this crisis integrated resource allocation for the increased amount of infected patients, while maintaining an adequate response to other severe and life-threatening diseases. Though cardiothoracic patients are at high risk for Covid-19 severe illness, postponing surgeries would translate in increased mortality and morbidity. We reviewed our practice during the initial time of pandemic, with emphasis on safety protocols. Methods: From March 11st to May 15th 2020, 148 patients underwent surgery at the Department of Cardiothoracic Surgery of CHUSJ. The clinical characteristics of the patients were retrospectively registered, along with novel containment and infection prevention measures targeting the new Corona Virus. Results: The majority of adult cardiac patients were operated on an urgent basis. Hospital mortality was 1.9% (n = 2 patients). Most of adult thoracic patients were admitted from home, with a diagnosis of neoplasic disease in 60% patients. Hospital mortality was 3.3% (1). Fifteen children underwent cardiothoracic surgery. There was no mortality. The infection prevention procedures applied, totally excluded the transmission of Covid-19 in the Department. Conclusion: While guaranteeing a prompt response to emergent, urgent and high priority cases, novel safety measures in individual protection, patients circuits and pre-operative diagnose of symptomatic and asymptomatic infection were adopted. The surgical results corroborate that it was safe to undergo cardiothoracic surgery during the initial time of Covid-19 pandemic. The new policies will be maintained while the virus stays in the community.
Letter to the editorTry as we might to make the manuscript selection process as objective as possible, the crapshoot element is unquestionable. Prospective papers are being submitted more frequently than ever, which has broadened the number of reviewers. Medical students and senior faculty alike are being tasked with assessing manuscripts. Different levels of experience, knowledge and variable personal research interests introduce undeniable biases in how papers are ultimately critiqued. We’ve become keenly aware of the importance of evaluating research techniques and the studies themselves for risks of biases; PRISMA, MINORS, MOOSE and ROBINS tools lead a growing list of objective protocols and assessments.1,2,3,4 Have we ever thought of addressing potential biases in how we actually select articles for publication?Obviously, this would be no simple task, but that shouldn’t be a deterrent to making improvements in the process where possible; personal connections come to mind in this regard. Generally speaking, very little is being done to prevent reviewers from being aware of who the authors are and where they’re coming from. Additionally, many submission platforms allow for the selection of preferred reviewers as well as the ability to decline undesired reviewers. While these tendencies are understandable for multiple reasons, their potential to introduce personal biases is noteworthy. For the sake of argument, let’s assign a very simple “risk of personal bias reduction score” for a journal’s manuscript submission platform: One point is given for a) maintaining author confidentiality, b) maintaining institution/location confidentiality and c) avoiding the option to select or decline particular reviewers. As such, the scores range from 0 to 3, with 3 being the most favorable.So how are we doing? Table 1 shows a list of the top 20 otolaryngology journals to date as determined by the h -index, an increasingly popular measure of journal quality based on the number of publication citations.5 Ten of the 19 eligible journals did not take any measures to reduce the potential for personal biases, thus scoring 0. Eight journals earned one point for avoiding the opportunity to select or decline reviewers. Of note, several journals cite this feature as a means of reducing bias; encouraging the submitting author to target “unbiased” reviewers. The value of this is debatable as this feature can easily be used paradoxically. Lastly, one journal scored two points for blinding the reviewers to both the author names and locations.It may seem trivial at first glance, as we’ve grown so accustomed to these aspects of the submission process, but it really isn’t. The notion that editors reviewing manuscripts are immune to biases from prior personal connections and experiences would be extremely shortsighted. Do we really think a given reviewer can assess a submission from a beloved former trainee in a reliably unbiased fashion? How about a manuscript from an institution with which there was a falling out of some kind? These themes are getting increasingly acknowledged in academic publishing, with growing numbers of journals implementing safeguarding measures. At most, there appears to be a nascent interest in addressing these topics within otolaryngology field. With rejection rates at all-time highs, it behooves us to reflect upon what can be done to ensure that the best manuscript wins: Who the authors are, who they know, and where they’re from shouldn’t be significant factors. As it stands currently, our submission platforms leave open avenues for personal connections to have a considerable influence. Reforming these potential biases, or at the very least acknowledging them, is in order.

Wenhui Zhao

and 6 more

Drought has become one of the major constraints on agricultural development, particularly in areas lacking water. Studying the effects of different water stresses on photosynthesis, growth, yield, water use efficiency (WUE) and water productivity (IWP) of winter wheat will provide scientific irrigation strategies for developing water-saving agriculture. According to the water field capacity, four different water stress levels were set, i.e., 30–40% of water field capacity (severe stress), 40–50% (moderate stress), 50–60% (mild stress) and 60–80% (well-watered), through an automatic irrigation system by controlling the irrigation amount. The results showed that the diurnal and seasonal changes in photosynthetic parameters such as net photosynthetic rate (Pn), intercellular carbon concentration (Ci), stomatal conductance (Gs), and transpiration (E) significantly decreased under moderate and severe stress. The Pn of mild stress only slightly decreased compared to that of well-watered and was even higher after May 16th. As a result, the dry biomass and 1000-grain weight under mild stress increased 2.07% and 1.95% compared with well-watered. Under all water stresses, the heights and straw weights of the winter wheat significantly decreased. It was also found that mild water stress increased the WUE and IWP, which further resulted in the negligible decrease of the fresh weight of the aboveground biomass, dry biomass weight, spike weight, grain weight. Conversely, WUE and IWP significantly decreased under moderate and severe stress, which can affect the growth of winter wheat. So the fresh weight of the aboveground biomass, dry biomass weight, spike weight, grain weight also significantly decreased under moderate and severe stress. Thus, mild stress results in the optimal use of water resources without a significant reduction in yield in the North China Plain. Therefore, mild stress can be considered as a suitable environment for winter wheat growth in arid areas.
Figure 1 (2)

Aviram Hochstadt

and 13 more

Background: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of longitudinal diastolic strain time (Dst) with the routine echocardiography diastolic parameters and to estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. Methods: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy were included. Echocardiography, including Global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity were determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. =diastolic time (ms) measured. Results: Among 69 patients, 67 (97.1%) were females with a mean age 52±13years. Diastolic strain timeDst measurement was significantly associated with the standard routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3 . Both in a univariate and a multivariate analyses the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (p<0.04). Conclusions: Among breast cancer patients, Dst time showed high correlation to standard the routine diastolic echocardiography parameters. Relative reductionChange in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Sergey Moiseev

and 10 more

Objectives. We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Methods. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. Results. The median concentrations of MAC, C5a, C3a, and factor B were higher in active AAV patients (p<0.001). Achievement of remission was associated with reductions in C3a (p=0.005), C5a (p=0.035), and factor B levels (p=0.045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered in the meta-analysis. Plasma MAC, C5a, and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Conclusion. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.

Amer Harky

and 3 more

Dear Editor,We read with interest the published article by Ikeda et al. [1], they performed thoracic endovascular aortic repair (TEVAR) in a patient with Marfan syndrome (MFS) for acute complicated type B aortic dissection (TBAD) during COVID-19 pandemic.The evidence around TEVAR for MFS is scarce and open repair remains the gold treatment[2]. During the COVID-19 pandemic, many patients are either being denied treatment or given inferior options on the basis of age, comorbidities and risk of COVID pneumonia; however, the guidelines for aortic intervention in the United Kingdom have remained largely unchanged from pre-COVID-19 era [3]. Our questions to the authors relate to whether their solution was an unnecessary compromise. There is no clear indication defined in their case as a cold leg doesn’t necessary means an ischaemic limb. The TEVAR procedure performed aiming to minimise hospital stay, yet this approach may have put the patient at higher risk of developing paraplegia and visceral organ malperfusion, while compromising her long-term care.There is need to clarify if she had risk factors that prone her to a higher risk acquiring severe COVID-19 which necessitated deviating from the traditional open surgery recommended for MFS patients with TBAD [2]. The authors did not report on renal function, evidence of bowel malperfusion or whether there was resistant hypertension that needed immediate intervention. If the need to expediate intervention was the fear of limb ischaemia, is it conceivable a femoro-femoral bypass could have saved the limb and definitive open surgery on her aorta could have been performed at a later stage, especially since she was haemodynamically stable.Moreover, as Marfan-diseased aortas are prone to further dilatation, we believe their justification for opting for endovascular repair should also have been more balanced, exploring the know high rate of long-term TEVAR-associated complications in MFS patients including endoleaks, retrograde dissection, stent-graft-induced new entry tears, surgical conversions and reintervention. There is also need for imaging follow-up to assess the success of TEVAR and early detection of aforementioned complications.

Browse more published preprints

The best features for modern research publishing

Behind the editor and beautiful interface, Authorea is an incredibly powerful platform. Here are some features that make it the most advanced tool out there for publishing all your research outputs.

Host data

Host and Publish Data

Store and publish all your research outputs such as code, figures, notebooks, and posters

Multiple markup languages

Multiple Markup Languages

LaTeX, Markdown, Rich text, Javascript: you can add many formats to a single document

History view


Add new versions, roll back changes, and see how a document came together over time

Hosted installation

White label and custom domains

Whether you run a journal or a research group, you can customize the look and feel of your portal pages

Mint doi

Make your work citeable

Receive a digital object identifier (DOI) for anything you upload on Authorea. Use it to get credit for all your research outputs

Advanced export and journal styles

Journal-integrated preprints

Directly submit to journals. Associate your preprints with your target journals.


Fork documents

Authorea stores the entire history of a document using Git, an advanced version control system



Start from templates for leading conferences, institutions, and journals

Direct submissions

Powerful document upload

Upload and host any filetype. Convert documents from Word, PDF, and LaTeX

Collaborate  product

Open Collaborative Review

Explore new ways to peer review and improve your content

Equations editor

Mathematical notation

Insert equations using a handy equations editor or type in LaTeX



Discuss changes with collaborators in real time

24x7 support

24x7 support

Authorea's support team is available via chat 7 days a week

Interactive figures

Interactive Figures

Add rich media to your research documents to make them come alive on the web

Integrations with ipython

Integrations with Jupyter, Plotly, and more

Publish your data-driven interactive notebooks with Authorea

Figure management

Advanced Export and Journal Styles

Export your work in one click to hundreds of different styles in PDF, Word, LaTeX, or Zip

Learn more about the product

What people are saying