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Hyuntae Na

and 2 more

Crystallographic B-factors provide direct dynamical information on the internal mobility of proteins that is closely linked to function, and are also widely used as a benchmark in assessing elastic network models. A significant question in the field is: what is the exact amount of thermal vibrations in protein crystallographic B-factors? This work sets out to answer this question. First, we carry out a thorough, statistically sound analysis of crystallographic B-factors of over 10,000 structures. Second, by employing a highly accurate all-atom model with the well-known CHARMM force field, we obtain computationally the magnitudes of thermal vibrations of nearly 1,000 structures. Our key findings are: (i) the magnitude of thermal vibrations, surprisingly, is nearly protein-independent, as a corollary to the universality in vibrational spectra of globular proteins established earlier; (ii) the magnitude of thermal vibrations is small, less than 0.1 Å2 at 100 K; (iii) the percentage of thermal vibrations in B-factors is the lowest at low resolution and low temperature (<10%) but increases to as high as 60% for structures determined at high resolution and at room temperature. The significance of this work is that it provides for the first time, using an extremely large dataset, a thorough analysis of B-factors and their thermal and static disorder components. The results clearly demonstrate that structures determined at high resolution and at room temperature have the richest dynamics information. Since such structures are relatively rare in the PDB database, the work naturally calls for more such structures to be determined experimentally.
Dylan K Wainwright et al. indicated high-performance Tuna platform for designing autonomous underwater vehicles [1]. Although their research will be useful, they should focus on the role of fins. Vadim Pavlov, et al. described hydraulic control of tuna fins [2]. During the late 18th century, wing designs were based on anatomical studies on dolphins, trout and tuna by the “father of aerodynamics”, Sir George Cayley [3,4]. Fish that are adapted for fast swimming, like tuna, are generally fusiform in shape and this is considered an efficient, hydrodynamic shape [5,6]. The hydraulic-fin-manufacture utilized multiple small fins instead of large hydraulic fins through the experiment for adopting better boat stabilizers [7]. By using two, four or six smaller active fins grouped together, the more small fins system produces better results without causing drag and slowing boats [7]. Tuna has such efficient hydrodynamic multiple small fins including 1st dorsal fin, 2nd dorsal fin, finlets, caudal fin, pelvic fin, pectoral fin, and anal fin. Every tuna fin may have the special role for better performance in stabilization of any vehicles.References:1. Dylan K Wainwright and George V Lauder 2020 Bioinspir. Biomim.15 0350072. Vadim Pavlov, et al., Hydraulic control of tuna fins: A role for the lymphatic system in vertebrate locomotion, Science, 21 Jul 2017, Vol.357, Issue 6348, pp.310-3143. Bio-mimetic Drag Reduction – Part 2: Aero- and Hydrodynamics, March 31, 2012 Eric Pickhartz, The ‘Tuna Robot’ is the Navy’s Newest Underwater Drone, July 4, 2014 Kirk Janowiak, Are fish aerodynamic?, Jan 12, 2015 High-Performance Active Fin Stabilizers Improve Boat Speed and Performance, Feb 21, 2017

Yanan Sun

and 5 more

E,E-2,4-hexadienal is probably a precursor of secondary organic aerosol (SOA) and plays an important role in the atmospheric chemistry. Its main degradation routs are the reactions with OH, Cl, NO3 as well as photolysis. Atmospheric hydroxyl radical, as the most important oxidant, generally controls the removal of volatile organic compounds (VOCs) in the atmosphere. Thus, the quantum chemical calculations are used to investigate the reaction mechanism of E,E-2,4-hexadienal with hydroxyl radical, which would give better understanding for the main degradation products. The reaction paths of E,E-2,4-hexadienal with OH radical have been calculated accurately at the BMC-CCSD//M06-2X/6-311G (d, p) level at atmospheric pressure and room temperature. There are six hydrogen abstraction and four carbon addition paths at the first stages of this reaction. Due to the low energy barrier and reaction exotherm, the ten paths would contribute to the total reaction. Furthermore, the peroxy (RO2) and alkoxy (RO) radicals from the most important adduct IM1(CH3CHOHCHCH=CHCHO) would be formed in the atmospheric environment. The reaction mechanism of the peroxy radical (CH3CHOHCHO2CH=CHCHO) with NO, NO2, HO2, and self-reaction have been studied by using the same quantum chemical methods. And the reaction paths of alkoxy radical (CH3CHOHCHOCH=CHCHO) have been also originally studied. The subsequent reactions play a key role in the cycling of atmospheric radicals, production of ozone, and SOA formation. What’s more, the reaction mechanism of this study accords with the reported experimental observations.

Shahid Dar

and 2 more

Globally, urban wetlands are facing immense pressure of land use land cover changes (LULCCs) and associated water quality degradation that is severely affecting the trophic status of these pristine ecosystems. This study analyzed water quality degradation resulting due to the land system changes in the vicinity of Khushalsar, an urban wetland, in Srinagar city from 1980-2017. The analysis of satellite data indicated that the wetland has lost ~18.1 ha from 1980-2017. During the same period the urban area within the wetland increased from 0.2% to 16.5%. The land cover changes assessed in the immediate vicinity of wetland indicated an increase of 119% in built-up and 62.8% in roads. The analysis of surface water quality of the wetland showed much greater degradation of Khushalsar wetland. The Trophic State Index (TSI) ranged from 73.4-84.6 thereby indicating the hyper-eutrophic nature of the wetland. A snapshot of comparative water quality data from 2002-2018 revealed that the mean concentration of NO3–N increased from 219-433 µg L-1 and total phosphorus (TP) increased from 135.4-1236 µg L-1 indicative of continuous nutrient enrichment. Hierarchical cluster analysis (HCA) clustered 8 sampling sites into 4 groups based on likeness of water quality characteristics. Similarly, discriminant analysis (DA) showed the formation of similar patterns of clusters, authenticating the outcomes of HCA. Wilk’s λ quotient dispersion highlighted the role of nutrients and ions in the development of clusters. Principal component analysis (PCA) formed three principal components (PC’s) accounting for a cumulative variance of 90.61%.

Masroor Sharfi

and 5 more

Here we report an extremely rare case of congenitally corrected transposition of great arteries (CCTGA) associated with Interrupted aortic arch (IAA) type A and ventricular septal defect (VSD) in a preterm baby. Antenatally diagnosed as large VSD and severe Coarctation of aorta. Echocardiogram done revealed that left ventricle with the mitral valve lay on the right side in continuation with the venous right atrium and was connected to the pulmonary artery. The right ventricle lay on the left in continuation with the arterial left atrium and was connected to the aorta. Smallish transverse arch with Interruption of aorta below the left subclavian artery. Large VSD with bidirectional shunt. Small PDA with restrictive right to left flow. As far we know, only one similar case was reported earlier by Cottrell, at el. (4). At that time the initial diagnosis was done by cardiac angiography as 2D color echocardiography was not available at their center, after one year they were able to use echocardiogram and same diagnosis was confirmed. In our case despite the complex anatomy we were able to diagnose our case by 2D color Echocardiogram. The Echocardiogram images and loops were so clear and confirmative that no other cardiac imaging was required. Baby was stable clinically on prostaglandin and underwent successful aortic arch repair (end to end anastomosis) and PA banding. We believe that Echocardiography still is a basic tool for diagnosis of complex congenital cardiac anomalies specially in centers where other higher diagnostic modalities are still not available.

Yi Du

and 3 more

Preferential flow plays an important role in soil water retention, movement, and solute transport. Heterogeneity, uncertainty, and the scale of preferential flow are the focus of the current research. The multi-index method and preferential flow classification method were used to identify and quantify preferential characteristics and flow types at three points on a slope in the upstream portion of a drinking water supply area. Results show that the infiltration depth of the preferential flow on the hillslope is about 400 mm. The preferential flow fraction of the stain profile ranges from 56.6 to 74.8%. The result of multi-index evaluation indicates that the weight of the peak value of the stained area and coefficient of variation are the two indexes that have a greater influence on the preferential flow. Regarding the difference in preferential flow at different slope positions, the peak value of the stained area at mid-slope is higher and the coefficient of variation is lower, indicating that the preferential flow at mid-slope is more developed than upslope and downslope. The results of the quantitative analysis of preferential flow types indicate that the dyeing depth can be divided into three parts with dividing points at 100 and 275 mm due to the distribution of the stain width. The main flow type is macropore flow, especially macropore flow with mixed interaction, accounting for 49.8, 52.2, and 61.3% of the flow types at upslope, mid-slope, and downslope locations, respectively. The interaction between macropores gradually decreases with increasing soil depth and increasing elevation. As for the factors influencing preferential flow type, correlation analysis found that the higher the soil moisture content, the stronger the interaction between macropores. Influenced by bulk density, saturated conductivity, and porosity, matrix flow in the soil is relatively stable with a depth of approximately 10 cm. The study results can provide a reference for subsequent research on the preferential infiltration mechanism at different slope positions and the transport characteristics of water and nutrients.

chunyuan wang

and 6 more

Drought is one of the most significant natural disasters in the arid and semi-arid areas of China. The growth stages of populations or plant organs often differ in how they respond to drought and other adversities. At present, little is known about size- and leaf age-dependent differences in the mechanisms of shrubs-related drought resistance in China’s deserts. We studied Artemisia ordosica Krasch to evaluate its photosynthesis responses to drought stress. A field experiment conducted in Mu Us Desert, Ningxia, China. Rainfall was manipulated by installing outdoor shelters, with four rainfall treatments applied to 12 plots (each 5  5 m). There were four precipitation levels CK (ambient), -30%, -50%, -70%, each with three replications. Taking individual crown size as the dividing basis, the responses of the plants’ photosynthetic systems to drought were measured at different growth stages, i.e. large-sized (>1 m2), medium-sized (0.25-1 m2), small-sized (<0.25 m2). In the meanwhile, leaves were divided into mature leaves and new ones for separately measurement. Our results showed that (1) under drought stress, the transfer efficiency of light energy captured by antenna pigments to the PSII reaction center decreased, and the heat dissipation capacity increased simultaneously. To resist the photosynthetic system damage caused by drought, A. ordosica enhanced free radical scavenging by activating the antioxidant enzyme system. (2) The threshold for a reduction in rainfall was 70%; beyond this value, the adaptive regulation of the photosynthetic system in A. ordosica failed. (3) The growth stages and leaves age led to differences in the photosynthetic system reaction to drought. Small A. ordosica plants could not withstand severe drought stress (70% rainfall reduction), whereas large A. ordosica individuals could absorb deep soil water to ensure their survival. Under mild drought stress, tender (younger) leaves had a greater ability to resist drought than older leaves, whereas the latter were more resistant to drought under severe stress.

Alessio Notari

and 1 more

We analyze risk factors correlated with the initial transmission growth rate of the recent COVID-19 pandemic in different countries. The number of cases follows in its early stages an almost exponential expansion; we chose as a starting point in each country the first day $d_i$ with 30 cases and we fitted for 12 days, capturing thus the early exponential growth. We looked then for linear correlations of the exponents $\alpha$ with other variables, for a sample of 126 countries. We find a positive correlation, {\it i.e. faster spread of COVID-19}, with high confidence level with the following variables, with respective $p$-value: low Temperature ($4\cdot10^{-7}$), high ratio of old vs.~working-age people ($3\cdot10^{-6}$), life expectancy ($8\cdot10^{-6}$), number of international tourists ($1\cdot10^{-5}$), earlier epidemic starting date $d_i$ ($2\cdot10^{-5}$), high level of physical contact in greeting habits ($6 \cdot 10^{-5}$), lung cancer prevalence ($6 \cdot 10^{-5}$), obesity in males ($1 \cdot 10^{-4}$), share of population in urban areas ($2\cdot10^{-4}$), cancer prevalence ($3 \cdot 10^{-4}$), alcohol consumption ($0.0019$), daily smoking prevalence ($0.0036$), UV index ($0.004$, smaller sample, 73 countries), low Vitamin D serum levels ($0.002-0.006$, smaller sample, $\sim 50$ countries). There is highly significant correlation also with blood type: positive correlation with types RH- ($3\cdot10^{-5}$) and A+ ($3\cdot10^{-3}$), negative correlation with B+ ($2\cdot10^{-4}$). We also find positive correlation with moderate confidence level ($p$-value of $0.02\sim0.03$) with: CO$_2$/SO emissions, type-1 diabetes in children, low vaccination coverage for Tuberculosis (BCG). Several of the above variables are correlated with each other and likely to have common interpretations. We thus performed a Principal Component Analysis, in order to find the significant independent linear combinations of such variables. We also analyzed the possible existence of a bias: countries with low GDP-per capita, typically located in warm regions, might have less intense testing and we discuss correlation with the above variables

Sérgio Dortas Jr

and 4 more

Background: Patients with chronic urticaria (CU) often report an impaired quality of life (QoL). Although a positive effect of addressing spirituality in health care has been proved in several chronic diseases, its potential role in CU has received no attention. This study evaluated spirituality and QoL in CU subjects with different control levels. Methods: In a single-centre observational study, 100 CU subjects were investigated using Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, Chronic Urticaria Quality of life Questionnaire (CU-Q2oL) and Urticaria Control Test (UCT). Results: Of 100 subjects, 82 were female and 18 were male. It was observed that subjects with not controlled CU presented FACIT Sp-12 meaning/peace (p = 0.004) significantly lower, and CU-Q2oL (p <0.0001) significantly higher (worst QoL) than subjects with controlled CU. There was no difference in the FACIT Sp-12 faith (p = 0.43) between groups. There was moderate direct correlation between FACIT Sp-12 faith and FACIT Sp-12 meaning/peace (r = 0.483; p <0.0001; n = 100). There was a significant strong inverse correlation between the CU-Q2oL and the UCT (r = -0.762; p <0.0001; n = 100). No correlation was found between the FACIT Sp-12 faith and CU-Q2oL, neither with UCT. Conclusion: No study has ever investigated the role of spirituality in managing patients with urticaria. Our findings support the impact of poorly controlled urticaria in spiritual well-being and QoL. Therefore, clinicians should pay more attention to spirituality among CU patients. We suggest that urticaria guidelines should include specific recommendations on spirituality assessment.

Xiaoting Song

and 5 more

Françoise Pirson

and 7 more

Background: There is in Europe variations in geographical exposures, sensitizations and related clinical allergic manifestations to pollens. This study analyzed the molecular profile of allergen sensitization of a cohort of birch and/or grass pollen allergic patients with or without pollen-related food allergy. Methods: Patients with birch and/or grass allergic rhino-conjunctivitis and/or asthma were included and submitted to standardized questionnaire, skin prick tests (aeroallergens and fresh foods) and serum IgE assays. Results: Based on clinical history, 74 patients were included with birch (n=10), grass (n=31) or mixed (n=34) pollen allergy. Mono-sensitization to pollen was seen in 10 % of patients. In the birch allergic group, Bet v 1 was the major allergen (100 %); 50 % were co-sensitized to grass pollen and 80 % had a plant food allergy. In the grass allergic group, 50 % were co-sensitized to birch pollen; major allergens were rPhl p 1, nPhl p 4, rPhl p 2, rPhl p 5 b, rPhl p 6 while 32 % had a plant food allergy. In the mixed pollen allergic population, rBet v 1, rPhl p 1, nPhl p 4, rPhl p 5b and rPhl p 2 were major allergens, and food allergy was present in 76 %. In the 3 groups, patients with food allergy (mainly oral allergy syndrome) had a stronger and higher prevalence of IgE-sensitization to birch pollen and Bet v 1 allergen. Conclusions: IgE sensitization to birch pollen is frequent in grass allergic patients: Bet v 1 represents a marker of cross-plant food allergy.

Matthew Wong

and 4 more

Aims: The primary aim was to identify predictors of home oxygen duration for preterm infants with chronic neonatal lung disease (CNLD). Secondary aims were to identify predictors of oxygen flow rates at discharge and the association of discharge oxygen flow rates with respiratory outcomes. Methods: Retrospective cohort of infants with CNLD requiring home oxygen in 2016 and 2017. Hazard ratios (HR) were estimated from Cox proportional hazards regression models in the entire cohort. Multiple linear regression models were used to examine the effects of maternal and infant variables and the effect of post-discharge factors on oxygen flow rate. Results: Home oxygen ceased in 149 infants at a median postmenstrual age (PMA) of 6.8 months (IQR 4.4) with 87.2% of infants weaned by 12 months. Shorter neonatal hospitalization predicted faster oxygen weaning at 9 months (HR 0.99, 95% CI 0.98-1.00, p=0.02) and 12 months (HR 0.99, 95% CI 0.98-1.00, p=0.02) PMA. Each mmHg increase in carbon dioxide partial pressure at term was associated with 4.99 mL/min more home oxygen (95% CI, 1.45-8.52, p=0.01). Infants born at a tertiary neonatal intensive care required 63.42mL/min more oxygen (95% CI, 2.03-124.82, p=0.04). Pulmonary hypertension and respiratory related hospital admission were associated with 139.83 mL/min (95% CI 12.56-267.10, p=0.03) and 18.40 mL/min (95% CI, 1.98-34.81, p=0.03) more home oxygen respectively. Conclusion: The best predictor of oxygen duration is length of neonatal hospital stay. Care should be taken to ensure infants with moderate to severe hypercapnia or pulmonary hypertension have adequate oxygen flow rates at discharge.

Nachiket Apte

and 9 more

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Wahaj Munir

and 3 more

Background: Acute type A aortic dissection (ATAAD), is a surgical emergency often requiring intervention on the aortic root. There is much controversy regarding root management; aggressively pursuing a root replacement, versus more conservative approaches to preserve native structures. Methods: Electronic database search we performed through PubMed, Embase, SCOPUS, google scholar and Cochrane identifying studies that reported on outcomes of surgical repair of ATAAD through either root preservation or replacement. The identified articles focused on short- and long-term mortalities, and rates of re-operation on the aortic root. Results: There remains controversy on replacing or preserving aortic root in ATAAD. Current evidence supports practice of both trends following an extensive decision-making framework, with conflicting series suggesting favourable results with both procedures as the approach that best defines higher survival rates and lower perioperative complications. Yet, the decision to perform either approach remains surgeon decision and bound to the extent of the dissection and tear entries in strong correlation with status of the aortic valve and involvement of coronaries in the dissection. Conclusions: There exists much controversy regarding fate of the aortic root in ATAAD. There are conflicting studies for impact of root replacement on mortality, whilst some study’s report no significant results at all. There is strong evidence regarding risk of re-operation being greater when root is not replaced. Majority of these studies are limited by the single centred, retrospective nature of these small sample sized cohorts, further hindered by potential of treatment bias.

Matthew Sussman

and 9 more

The recognition of fibrinolysis phenotypes in trauma patients has led to a reevaluation of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, however the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this study was to fill that gap. Methods: Data were retrospectively reviewed from 78 cardiac surgery patients. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (LY30 0.8-3.0%) and hyperfibrinolytic (LY30 >3%). Continuous variables were expressed as M ± SD or median (interquartile range). Results: The study population was 65±10 yrs old, 74% male, average body mass index of 29±5 kg/m2. Fibrinolytic phenotypes were distributed as physiologic=45%, hypo=32% and hyper = 23%. There was no obvious effect of age, gender, race, or ethnicity on the distribution of fibrinolysis phenotypes; 47% received AF. The time with chest tube during post-operative recovery was longer in those who received AF (4[3,5] days) vs no AF (3[2,4] days), P=0.037). All cause morbidity occurred in 51% of patients who received AF vs 25% with no AF (p=0.017). However, with AF vs no AF, apparent differences in median chest tube output (1379 vs 820ml, p=0.075), hospital LOS (13 vs 10 days, P=0.873), estimated blood loss (1100 vs 775 ml, P=0.127), units of transfused RBCs (4 vs 2], P=0.152) or all-cause mortality (5.4% [2/37] vs 10% [4/41], P=0.518) were not statistically significant. Conclusion: This is the first description of three distinctly different fibrinolytic phenotypes in cardiac surgery patients. In this population, the use of AF was associated with increased morbidity.

Arushi Singh

and 6 more

Background: Ibrutinib is associated with atrial fibrillation (AF), though echocardiographic predictors of AF have not been studied in this population. We sought to determine whether left atrial (LA) strain on transthoracic echocardiography could identify patients at risk for developing ibrutinib-related atrial fibrillation (IRAF). Methods: We performed a retrospective review of 66 patients who had an echocardiogram prior to ibrutinib treatment. LA strain was measured with TOMTEC Imaging Systems, obtaining peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS) on 4-chamber and 2-chamber views. Statistical analysis was performed with Chi-square analysis, T-test, or binomial regression analysis, with a p-value < 0.05 considered statistically significant. Results: Twenty-two patients developed IRAF (33%). Age at initiation of ibrutinib was significantly associated with IRAF (65.1 years vs. 74.1 years, p = 0.002). Mean ibrutinib dose was lower among patients who developed IRAF (388.2 ± 121.7 vs. 448.6 ± 88.4, p = 0.025). E/e’ was significantly higher among patients who developed IRAF (11.5 vs. 9.3, p = 0.04). PALS was significantly lower in patients who developed AF (30.3% vs. 36.3%, p = 0.01). On multivariate regression analysis, age, PALS and PACS were significantly associated with IRAF. On multivariate regression analysis, only PACS remained significantly associated with IRAF while accounting for age. Conclusions: Age, ibrutinib dose, E/e’, and PALS on pre-treatment echocardiogram were significantly associated with development of IRAF. On multivariate regression analyses, age, PALS and PACS remained significantly associated with IRAF. Impaired LA mechanics add to the assessment of patients at risk for IRAF

James Hummel

and 1 more

We thank Medina et al. for their interest in our recent work on QTc prolongation associated with treatment of COVID-19 patients with hydroxychloroquine and azithromycin. As they appropriately point out in their letter, genetic variation is likely a significant determinant of QT prolongation in the population at large and in COVID-19 patients specifically. While drugs causing acquired long QT syndrome and torsades de pointes are generally blockers of IKr, repolarization results from the aggregate of multiple inward and outward currents. Patients with sub-clinical defects in any of these ion channels can have normal or only slightly prolonged baseline QT intervals, but may possess decreased repolarization reserve leading to an exaggerated response to IKr blockade (1).  In our study, a baseline QTc of > 460 ms was associated with excessive QTc prolongation, and this likely represents a group of patients with sub-clinical cardiac ion channel mutations (so called “first hit”) (2). We also agree that many patients with latent mutations demonstrate a normal baseline QT, which gets prolonged with the addition of a drug or a change in the clinical condition “second hit” (3). The patients in our study who exhibited QTc prolongation were generally acutely ill, and displayed “multiple hits” that led to QTc prolongation and it is certainly plausible that many may have had sub-clinical cardiac ion mutations. We therefore wholeheartedly agree that pharmacogenetics should be considered in studies of drug-induced QT prolongation, however this information is rarely available to include for acutely ill patients. And while it makes sense to obtain genetic profiles prior to administration of QT-prolonging medications, that can only be performed in the elective outpatient setting, while taking into consideration medical, ethical and social issues related to asymptomatic genetic screening (e.g. cost, reimbursement, informed consent, etc…). There is significant interest in building genomic databases, and when this becomes a reality for the population at large we believe that genetic information should certainly be included in studies of QT prolongation.Roden DM Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006 Jan; 259(1):59-69.Napolitano C, Schwartz PJ, Brown AM, et al. Evidence for a cardiac ion channel mutation underlying drug-induced QT prolongation and life-threatening arrhythmias. J Cardiovasc Electrophysiol. 2000;11:691–6Sauer AJ and Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012;125:1684-94.

Roberto CHIESA

and 3 more

During the first phase of COVID-19 pandemic in Italy, several strategies have been taken to deal with the pandemic outbreak. The Regional Authority of Lombardy remodeled the hospitalization system in order to allocate appropriate resources to treat COVID-19 patients and to identify “Hub/Spoke” hospitals for highly specialized medical activities. The Hubs hospitals were required to guarantee full time evaluation of all patients presenting with cardiovavascular diseases with an independent pathway for patients with suspect or confirmed COVID-19 infection. San Raffaele Hospital was identified as Hub for cardiovascular emergencies and the Vascular Surgery Department was remodeled to face this epidemic situation. Surgical treatment was reserved only to symptomatic, urgent or emergent cases. Large areas of the hospital were simultaneously reorganized to assist COVID-19 patients. During this period, 135 patients were referred to San Raffaele Vascular Surgery Department. COVID-19 was diagnosed in 24 patients and, among them, acute limb ischemia was the most common cause of admission. At this time, the COVID-19 trend is in decline in Italy and the local authorities reorganized the health care system in order to return to normal activities avoiding new escalations of COVID-19 cases. Several strategies have been taken to ensure the safety of the San Raffaele hospital, and maintaining potentially suspected patients with COVID-19 separated from other patients. The aim of this paper is to report the remodeling of the Vascular Surgery Department of San Raffaele Hospital as regards the strategies of preparation, escalation, de-escalation and return to normal activities during the COVID-19 pandemic.

Jose Lemus Calderon

and 5 more

INTRODUCTION: The SARS-CoV-2 coronavirus pandemic has caused more than fifteen million infections worldwide. Our aim is to investigate the differentiating characteristics in asthmatic patients with SARS-CoV-2 infection in the community of Castilla la Mancha. METHODS: We used the Savana® software and its algorithm based on Big Data and artificial intelligence, performed a retrospective search of the diagnoses of COVID 19 and asthma in the digitized medical records with positive RT-PCR results for SARS-CoV-2, and analysed the demographic characteristics, comorbidities, hospitalization data and deaths. RESULTS: 6,310 patients with positive RT-PCR for SARS-CoV-2 were selected, of which 577 had a diagnosis of asthma with a prevalence of 9.14%. The mean age in SARS-CoV-2 (SC2) was 59 ±19 years of age and in SARS-CoV2-asthma (SC2-A) 55 ±20 years of age. SC2 included 2983 (41%) men and 3327 (59%) women, while SC2-A included 198 (31%) men and 379 (69%) women. High blood pressure (BP) was the most common comorbidity in both groups (51%). 2,164 SC2 (34.2%) and 131 SC2-A (22.7%) required hospitalization with an asthma prevalence of 6.05%. 250 SC2 (3.96%) and 21 SC2-A (3.64%) died. CONCLUSION: The prevalence of asthma in our SARS-CoV-2 positive RT-PCR population was 9.14% and 6.05% in hospitalized patients. HBP is the most frequent comorbidity in both groups, and smoking is the only one with significant differences, more frequent in asthmatics. Mortality is lower in patients with asthma
Drug hypersensitivity reactions (DHRs) represent a global threat to healthcare systems due to their incidence, with a significant increase over last years1. DHR figures are overestimated in the general population since less than 40% of cases initially labelled as allergic can be confirmed as such when evaluated in an allergy unit2. Achieving an accurate diagnosis is complex and time consuming; besides, tests must be tailored to specific clinical manifestations and underlying mechanisms and will depend on the culprit drugs. Diagnosis often requires performing drug provocation tests (DPTs), which are especially problematic for severe reactions, making management of these patients challenging and expensive for the health care system.Clinically, DHRs are classified into immediate and non-immediate, based on the time interval between drug exposure and onset of the symptoms3. The most severe immediate reaction is anaphylaxis. This issue of the journal has been dedicated o drug hypersensitivity, which is becoming a major public health issue during the last decade, especially with the introduction of biologicals to medicine. Bilo et al. 4 evaluated the anaphylaxis mortality rate in Italy from 2004 to 2016 and found an average mortality rate for definite anaphylaxis (ICD-10 code) of 0.51 per million population per year, mostly due to the use of medications (73.7%), although in 98% of the cases culprit drugs were not identified. Regarding non-immediate reactions, one of the most challenging diagnoses is drug reaction with eosinophilia and systemic symptoms (DRESS), which is sometimes difficult, at an early stage, due to overlapping clinical symptoms with maculopapular exanthema (MPE). Pedruzzi et al. 5 identified 7 microRNAs (miRNAs) that correctly classified DRESS or MPE patients and were associated with keratinocyte differentiation/skin inflammation, type I IFN pathway viral replication, ATP-binding cassette transporters, and T lymphocyte polarisation, being all of them potential biomarkers. Non-immunologically mediated adverse reactions, such as attention-deficit/hyperactivity disorder (ADHD) are reported by Fuhrmannet al. 6 in association with systemic H1-antihistamines administration in school-age children, especially the 1st generation agents.The mechanism underlying DHR and the reason why patients treated with the same drug develop a tolerance response or an immediate or non-immediate DHR is not completely understood (Figure 1). Therefore, the prediction of who may experience a DHR, and if so, in what form, remains clinically obscure for most drugs. Goh SJR et al. 7 elegantly analyse this complexity, using non-immediate reactions to penicillins as a model. They focus on the understanding of the role of nature of the lesional T cells, the characterisation of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen-processing and presentation pathway to stimulate these deleterious responses.Regarding specific drugs involved in allergy, betalactam antibiotics (BL) are the most frequent culprit, being many reactions mediated by IgE. This type of reaction varies among patients, with some reacting only to one BL and others to several of them; it tends to change over time and differs between European countries, depending on BL consumption. Nowadays, amoxicillin (AX), alone or in combination with the β-lactamase inhibitor clavulanic acid (CLV), is the most often prescribed BL worldwide (Figure 2) and the most common elicitor of reactions in both children and adults. It is unclear why patients after the administration of AX-CLV develop selective hypersensitivity to AX, while tolerating CLV and vice-versa. Ariza et al. 8 generated drug-specific T-cell clones from AX- or CLV-selective immediate hypersensitivity patients and found that both AX- and CLV-specific clones were generated irrespective of whether AX or CLV was the culprit, although a higher secretion of Th2 cytokines (IL-13 and IL-5) was detected when clones were activated with the culprit BL compared with clones stimulated with the tolerated BL, in which higher secretion of Th1 cytokines (IFN-γ) was observed. Regarding selective non-immediate reactions to CLV, Copaescu A et al. 9 report on a cohort of patients with a history of non-immediate reaction to CLV, who demonstrated a delayed intradermal skin test response to CLV, 17% were allergic to both CLV and ampicillin, and 83% were selective reactors with good tolerance to AX. IFN-γ release enzyme-linked immunospot (ELISpot) was performed giving a sensitivity of 33%. Other drugs such as sulphonamides, either antibiotic or non-antibiotics are important triggers of non-immediate DHRs. Vilchez-Sanchez et al. 10 showed that lymphocyte transformation tests (LTT) can help avoid the performance of DPT with a sensitivity of 75%, a specificity of 100%, and negative and positive predictive values of 72.7% and 100%, respectively.There has been a great expansion in the use of biological agents (mainly monoclonal antibodies (mAbs)), and they have greatly improved the treatment landscape of hemato-oncologic, autoimmune, inflammatory and rheumatologic diseases. In parallel, the incidence rate of reported DHRs associated with these products has increased considerably within the last years, ranging from mild to life-threatening. Yang BC et al. 11 recommend risk stratification as the first step for managing patients with DHRs to these drugs. In cases with negative skin test and mild reactions, DPT is an option, and in moderate or severe reactions, desensitisation becomes the preferred approach. In cases with positive skin test, desensitisation is the recommended course of action, especially when there is no alternative medication. Desensitisation is also widely used in the management of immediate hypersensitivity reactions to chemotherapy agents, such as platinums. There is suspicion about the presence of a longer memory of tolerance in subsequent desensitisation protocols partially resembling the regulatory tolerance mechanisms induced by allergen immunotherapy. Tüzer et al. 12 demonstrate the possible role of IL-10 in desensitisation with platinums, as they found a dynamic change in serum IL-10 levels observed as an increase during desensitisation and a decrease in between the protocols.Finally, a wide spectrum of drugs has been considered for treatment of coronavirus disease 2019 (COVID-19) and all of them can potentially induce DHRs. Gelincik A et al .13 reviewed DHRs in COVID-19 times to these drugs, with knowledge mainly coming from previous clinical experience in patients not infected with COVID-19. As in other viral infections, skin symptoms, including exanthemas, may appear during the evolution of the disease, leading to differential diagnosis with DHRs. Whether COVID-19 can aggravate T–cell mediated DHRs reactions as some viruses is at present unknown.We can conclude that new drugs are continuously introduced into the markets and confirmed as inducers of hypersensitivity reactions. We still do not completely understand the mechanisms underlying many of these reactions and further studies for improving diagnostic and management are needed even in classic and well-studied drugs as BLs.Abbreviations: AX: Amoxicillin; CLV: Clavulanic acid; COVID-19: Coronavirus disease 2019; DHR: Drug hypersensitivity reactions; DPT: Drug provocation tests; DRESS: Drug reaction with eosinophilia and systemic symptoms; ELISpot: enzyme-linked immunospot; LTT: Lymphocyte transformation tests; MPE: Maculopapular exanthema.

Meilin Schaap

and 4 more

Introduction: To evaluate the long-term (5 years) effects of perioperative briefing and debriefing on team climate. We explored the barriers and facilitators of the performance of perioperative briefing and debriefing to explain its effects on team climate and to make recommendations for further improvement of surgical safety tools. Methods: A mixed-method evaluation study was carried out among surgical staff at a tertiary care university hospital with 593-bed capacity in the Netherlands. Thirteen surgical teams were included. Team climate inventory and a standardised evaluation questionnaire were used to measure team climate (primary outcome) and experiences with perioperative briefing and debriefing (secondary outcome), respectively. Thirteen surgical team members participated in a semi-structured interview to explore barriers and facilitators of the performance of perioperative briefing and debriefing. Results: The dimension ‘participative safety’ increased significantly 5 years after the implementation of perioperative briefing and debriefing (p = 0.02 (95% confidence interval 1.18–9.25)). Perioperative briefing and debriefing was considered a useful method for improving and sustaining participative safety and cooperation within surgical teams. The positive aspects of briefing were that shared agreements made at the start of the day and that briefing enabled participants to work as a team. Participants were less satisfied regarding debriefing, mostly due to the lack of a sense of urgency and a lack of a safe culture for feedback. Briefing and debriefing had less influence on efficiency. Conclusions: Although perioperative briefing and debriefing improves participative safety, the intervention will become more effective for maintaining team climate when teams are complete, irrelevant questions are substituted by customised ones and when there is a safer culture for feedback.

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.
To the Editor, For the EU funded project PERMEABLE (PERsonalized MEdicine Approach for Asthma and Allergy Biologicals SeLEction), which addresses the availability of and access to advanced therapy of asthma in children across Europe, we performed a survey including 37 major pediatric asthma and allergy centers between September 2019 and July 2020. In total, the centers contributing to the survey treated approximately 1.000 young patients with severe asthma in 25 major European countries and Turkey with biologicals. In the light of the Corona Pandemic, we extended our survey asking the responsible clinicians if they experienced a SARS-CoV-2 infection in any of the children they are caring for. The questions pertaining to Corona infections were asked between March and July 2020.Given the prevalence of SARS-CoV-2 infections in the general population and in children, one would expect that at least 1% of the patients would be affected (1). In fact, none of the centers was aware of any symptomatic COVID-19 case in their patient populations or any positive SARS-CoV-2 tests.This leads to the conclusion, that either SARS-CoV-2 infections have a mild or even asymptomatic course also in children with severe asthma or that children with severe asthma (and their parents) were extremely successful in avoiding SARS-CoV-2 infections. Thus, we investigated by structured interview, how centers in those 26 countries had instructed their patients to avoid COVID-19. Interestingly, only 4 European countries (UK, Ireland, Portugal and Malta) had a strict, so called shielding policy in place which followed a principle of maximal segregation of severe asthmatics from the rest of the population: not leaving the house at all, not attending school even when they reopened, wearing face masks also at home, and social distancing even with family members. All other countries followed the principle of continuing or even enforcing asthma treatment in patients and advising to follow the same Corona rules as the general population.Both strategies led to the same result: An absence of COVID-19 cases in children with severe asthma. We conclude from this observation, that shielding is not necessary in children with severe asthma as they and their families are perfectly able to avoid Corona infections. The harm done to children by enforcing seclusion, separation and stigmatization needs to be acknowledged. Deprivation of school, social contact and friends weights heavy on children and the absence of any COVID-19 cases in major European centers for severe asthma in children does not justify a policy of compulsory shielding of children with severe asthma, neither in the first nor in any further Corona wave.Michael Kabesch, M.D.University Children’s Hospital Regensburg (KUNO) at the Hospital St. Hedwig of the Order of St. John, University of Regensburg, Regensburg, Germany.Member of the Research and Development Campus Regensburg (WECARE) at the Hospital St. Hedwig of the Order of St. John, Regensburg, Germany.ReferencesStringhini S, Wisniak A, Piumatti G, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study [published online ahead of print, 2020 Jun 11]. Lancet . 2020;S0140-6736(20)31304-0.

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.

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.
This paper presents a complete design procedure, with an optimized feeding method, of two-dimensional slotted waveguide antenna arrays (2D SWAs). For a desired sidelobe level ratio, the proposed system provides a pencil shape pattern with a narrow halfpower beamwidth, large sidelobe level ratio (SLR), and very low sidelobe levels (SLL), which makes it suitable for high power microwave applications. The radiating slotted waveguide antennas use longitudinal slots, designed for a specified slidelobe level ratio and resonance frequency. The resulting two-dimensional slotted waveguide antenna array is formed by stacking a number of similarly designed radiating SWAs, and fed with an additional SWA. The proposed feeding method uses longitudinal coupling slots rather than the conventional inclined coupling slots, which can provide better values of SLR and easily obtain very low SLLs, in comparison with the conventional systems. The feeder dimensions and slots positions are deduced from the dimensions and total number of the radiating SWAs. For a desired SLR, the slots excitation in the radiating and feeder SWAs are calculated based on a specified distribution. Then, using simplified closed-form equations and for a desired resonance frequency, the slots lengths, widths, and their distribution along the length of the radiating SWAs and feeder SWA can be found. Two examples are illustrated with different number of slots and radiating elements, and one is fabricated and tested. Chebyshev distribution is used to estimate the excitations of the SWA slots in the examples. The obtained measured and simulated results are in accordance with the design objectives.

Emidio Sivieri

and 3 more

Background: High frequency (HF) oscillatory ventilation has been shown to improve CO2 clearance in premature infants. In a previous in vitro lung model with normal lung mechanics we demonstrated significantly improved CO2 washout by HF oscillation of bubble CPAP (BCPAP). Objective: To examine CO2 clearance in a premature infant lung model with abnormal lung mechanics via measurement of end-tidal CO2 levels (EtCO2) while connected to HF oscillated BCPAP. Design/Methods: A 40mL premature infant lung model with either: normal lung mechanics (NLM): compliance 1.0 mL/cmH2O, airway resistance 56 cmH2O/(L/s); or abnormal lung mechanics (ALM): compliance 0.5 mL/cmH2O, airway resistance 136 cmH2O/(L/s), was connected to BCPAP with HF oscillation at either 4,6,8,10 or 12 Hz. EtCO2 was measured at BCPAPs of 4,6 and 8 cmH2O and respiratory rates (RR) of 40,60 and 80 breaths/min and 6mL tidal volume. Results: HF oscillation decreased EtCO2 levels at all BCPAPs, RRs, and oscillation frequencies for both lung models. Overall mean±SD EtCO2 levels decreased (p<0.001) from non-oscillated baseline by 19.3±10.2% for NLM vs. 14.1±8.8% for ALM. CO2 clearance improved for both lung models (p<0.001) as a function of oscillation frequency and RR with greatest effectiveness at 40-60 breaths/min and HF at 8-12 Hz. Conclusions: In this in-vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO2 clearance as compared to non-oscillated BCPAP for both NLM and ALM. The significant improvement in CO2 clearance in an abnormal lung environment is an important step towards clinical testing of this novel respiratory support modality.

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