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Small non-coding RNA profile in anaphylaxis
Emilio Nuñez-Borque
Sergio Fernández-Bravo

Emilio Nuñez-Borque

and 6 more

May 15, 2020
A document by Emilio Nuñez-Borque, written on Authorea.
Stream_Application_V.1.0.
Luca Scognamiglio

Luca Scognamiglio

May 15, 2020
Autore: Luca ScognamiglioIntroduzione
Associations of Perinatal Factors with Childhood Asthma and Allergies: A Cross-Sectio...
Agnes Ellie
Yuexia  Sun

Agnes Ellie

and 6 more

May 15, 2020
ABSTRACT Background: Asthma, rhinitis, and eczema are becoming increasingly prevalent among children in China. Studies have shown that the perinatal period is critical and impacts children’s health. However, research on the associations between perinatal factors and childhood allergic diseases in China are few. Objective: To evaluate the associations between the home factors (dampness/ humidity, parental smoking, contact with animals, and renovation) and childhood allergic diseases around the perinatal periods in China. Method: This work is part of the China Child Health and Home (CCHH) study and is an analysis of data from a cross-sectional questionnaire investigation in urban Tianjin and rural Cangzhou, China, from 2013 to 2014. A total of 7,366 randomly selected kindergarten and elementary school children age 0-8 years old were investigated. The questions used in the study were modeled according to the Dampness in Buildings and Health (DBH) study conducted in Sweden. Results: The prevalence of children’s doctor-diagnosed asthma, rhinitis, and eczema were 4.1%, 9.5%, and 35.6%, respectively. There were associations between the indexes of dampness/humidity and allergic diseases, with an odd ratio of up to 4.02 at a 95% confidence interval: (1.87-8.64), after adjustment. The other perinatal factors (parental smoking, contact with animals, and renovation) also showed positive associations with the allergic conditions. Conclusion: The environmental factors around the perinatal period show strong associations with the allergic conditions discussed in this study. Further studies are needed to identify the biologic background and probable mechanisms for these associations.
Corticosteroid pulse therapy or additional intravenous immunoglobulin for patients wi...
zhouping wang
Feiyan Chen

zhouping wang

and 8 more

May 15, 2020
There have been no robust data from clinical trials to guide the clinician in the choice of therapeutic agents for the child with IVIG resistance, the treatment regimen for IVIG resistant patients varies between institutions, and the best option has not yet been established therefore. In this trial, a total of 955 patients with KD were selected and were initially treated with IVIG. (2g/kg), of whom 80 (8.38%) assessed as IVIG resistant were randomly divided into two groups: group A received second IVIG treatment (n = 40), group B received methylprednisolone pulse therapy (MPT, n = 40). The whole fever time, duration of fever after retreatment, hospital days, medical cost, readmission rate, and laboratory examination difference (△) were calculated. CALs outcomes were followed up over two years. Patients in MPT group had shorter fever after retreatment and lower medical costs, more rapid declines in CRP, N%, PLT levels, and more rapid rise in sodium, but had a higher incidence of treatment failure and CALs than the second IVIG treatment group in long-term follow-up. the MPT used to treat IVIG-resistant KD still need to be considered carefully.
The Independent and Interdependent Self-affirmations in  Action: Understanding their...

Ruchi Pandey

and 2 more

May 15, 2020
The study explored the role of two dissimilar familial and religious practices in distinctly shaping independent and interdependent self-affirmations in two value systems surfaced to protect self-integrity and self-worth challenged by the threats of COVID-19. A qualitative method was employed which recruited a heterogeneous sample of 19 participants (10 joint and 9 nuclear families) who reported the consequences of COVID-19 and the roles of familial and religious values in facing the pandemic threats through a semi-structured interview. Five themes were generated: the perceived strong threat of COVID-19, positive roles of joint familial values and the religious values, dissimilar roles of individualistic and collectivistic values as well as traditional and modern religious values. Threats were expressed in the experiences of anxiety, uncertainty and mood fluctuations. Interdependence, affiliation and support were joint familial values whereas worshipping, divine interpretation and spiritual practices denoted traditional religious values. Independence, scientific interpretations and personal focus were individualistic family values. Focus on explicit attributes denoted modern while divine interpretation, will of God and dependency on God reflected traditional religious values. Coexistence of independent and interdependent self-affirmations originating from two distinct familial and religious value systems was observed possibly due to the current transitions in the Indian society. KeywordsCOVID-19; Indian family; narrative thematic analysis; pandemic; religious and familial practices; self-affirmation; social practices; threat.
The failure process of the filled loess slope triggered by groundwater using a flume...
Jianqi Zhuang
YI Zhu

Jianqi Zhuang

and 6 more

May 15, 2020
Gully Stabilization and Highland Protection (GSHP) techniques are useful in preventing gully erosion and have been widely utilized in the Loess Plateau. Rolling backfill is used to fill ditches in remolded loess, which is an important part of gully stabilization and highland protection, but destroys the original loess structure and changes the circulation of groundwater and surface water leading to a rise in groundwater. Groundwater rising is an important factor for filled loess slope instability and can induce landslides. A test device was designed to study the process of water infiltration into the filled project and the failure process of the filled loess slope due to groundwater rising. First, the groundwater was uniformly infiltrated with water, then preferential seepage with the deformation and cracks appeared in the slope. The pore-water pressure response to the groundwater infiltration and the pore-water pressure in the front of the slope body sharply increased, especially near the sliding surface, while the pore-water pressure at the back of the slope sharply decreased during slope failure. The failure process of the experimental slope can be divided into three stages: settlement deformation, collapse deformation, and slope toe slide-flow or regressive failure. In the first and second stages, the deformation is vertical displacement as slope settlement, and the third stage deformation is mainly horizontal displacement in the direction of the free surface of the slope body. The filled slope failure is due to groundwater infiltration with suffusion erosion, saturated softening, and infiltration dynamics.
METHODOLOGY FOR ASSESSING THE OPPORTUNITY OF FLOODING OF FORMER OPEN-PITS IN THE CONT...
Izabela Maria Apostu
Maria Lazar

Izabela Maria Apostu

and 1 more

May 15, 2020
As a result of open-pit mining exploitations, impressive size gaps occur in the landscape. Their flooding leads to the occurrence of so-called open-pit lakes and represents an interesting way to reclaim the degraded land. Because there is still no way to evaluate the opportunity of flooding the open pits, a methodology for assessing this opportunity was developed in order to identify the open-pits that are suitable for flooding. For this purpose, more criteria have been established that allow a complex assessment of the flooding opportunity. The methodology also aims to ensure maximum safety conditions in the former mining perimeter, the socio-economic and cultural requirements of local communities and the harmonization of the land in accordance with adjacent ecosystems.
Use of Focused Intensive Care Echo in the diagnosis of Primary Cardiac Angiosarcoma
Jasmine Medhora
Graham Wilson

Jasmine Medhora

and 3 more

May 15, 2020
Focused Intensive Care Echo (FICE) is recommended in critically unwell patients to assess haemodynamic status and aid decision making. In certain circumstances, FICE can also be used as a diagnostic tool. We present a case where FICE identified a large left atrial mass in an intensive care patient with acute hypoxia and thromboembolic sequelae. This case demonstrates the importance of FICE in aiding diagnosis in complex patients where initial investigations are non-diagnostic. FICE is an essential skill for critical care physicians, and bedside echocardiography should be a standard investigation for all critical care patients.
Predicting the ideal Valve Size during Aortic Valve Replacement with Rapid Deployment...
Ali Al-Alameri
Alejandro Macias

Ali Al-Alameri

and 5 more

May 15, 2020
Sutureless/rapid deployment valves provide surgeons with a new tool for aortic valve replacement (AVR) therapy, which can simplify the procedure. A main concern being the development of a paravalvular leak. We retrospectively reviewed our Aortic Valve Replacement database, were able to identify 25 rapid deployment aortic valves (INTUITY Valve System, Edwards Life Sciences LLC, Irvine, Calif) that had documented intraoperative Transesophageal Echocardiographic Annular measurements. All valves were implanted in the Aortic position. In this cohort, only patients that had their native aortic valve replaced either isolated or as part of any additional procedure were included. Patients that underwent Intuity valve implantation for Redo Aortic valve replacement were excluded from this study. After review of 25 patients who underwent rapid deployment valve implantation in the aortic position, 36% of patients had the same size valve as the measured aortic annulus, 48% of patients had a valve implanted that was 1 mm different, and 16% of patients had 2 mm difference. The mean annular size based on intraoperative TEE was 22.4 mm (range: 21-28 mm). The mean valve size that we implanted was 23.3 mm (range: 21-27 mm). No statistically significant difference between the mean annular measurement and the valve size selected (0.9 mm , p = 0.8) were found. TEE is perhaps remains as one of our most important tool to further enhance valve sizing and appropriately guide one through a proper and safe deployment.
Random mutagenesis by insertion of error-prone PCR products to the chromosome of Baci...
Be Ye
Yu Li

Be Ye

and 5 more

May 15, 2020
Bacillus subtilis is an attractive host for directed evolution of the enzymes whose substrates cannot be transported across the cell membrane. However, generation of mutant library in B. subtilis still suffers problems of small library size, plasmid instability and heterozygosity. Here, large library of random mutant was created through inserting error-prone PCR (epPCR) product to the chromosome of B. subtilis. Specifically, epPCR product was fused with flanking regions and antibiotic resistant marker using a PCR-based multimerization method, generating insertion construct. epPCR product was integrated into chromosome via homologous recombination after insertion construct was transformed into the supercompetent cells of B. subtilis strain SCK6. The transformation efficiency of insertion construct was improved though increasing the number of competent cell and the length of flanking regions. A library containing 3.5×105 random mutant was construction using per μg insertion construct, which is sufficient for directed evolution. Moreover, the library generation process could be accomplished within one day. The effectiveness of this method was confirmed by improving the activity of Methyl Parathion Hydrolase (MPH) toward chlorpyrifos and to enhance the secretion level of MPH in B. subtilis. Taken together, present work provides a fast and efficient method to integrate epPCR product into the chromosome of B. subtilis, facilitating directed evolution and expression optimization of target protein.
Understanding  the perceived health outcomes of children during COVID-19 pandemic
Gyanesh Kumar Tiwari

Gyanesh Kumar Tiwari

and 5 more

May 15, 2020
The study explored the lockdown and quarantine on the perceived psychological distress and other life outcomes of children after the outbreak of COVID-19 in recent past. The study employed the Narrative Thematic Research Design and chose a heterogeneous sample of 20 full-time mothers to report the experiences of the restrictions of their children aged 9-11 years. These mothers were the primary source of data about the impacts of lockdown and quarantine on their children. A telephonic semi-structured interview protocol was used to collect data. Four themes were generated: poor social and emotional responsivity, decreased interest in studies and other creative activities, psychological distress symptoms and negative health outcomes. Anxiety, irritation, quarrelling behaviours, anger, frustration, low feeling, reduced interest in games, boredom etc. were observed in children. Sleep disturbances, complaints of indigestion and multiple complaints of body aches were major negative health outcomes. The findings showed a variety of negative psychological and health outcomes for children due to the extreme restrictions, uncertainty, apprehension, reduced positive engagement and lowered social connection after the outbreak of the pandemic. Preventive and protective measures are recommended with concerted efforts of parents, school and community to guard children against the ill-consequences of current and future pandemics. Keywords: children; COVID-19; life outcomes; pandemic; perceived psychological distress, narrative thematic analysis.
COVID-19 Antibody Surveillance Among Healthcare Workers in A Non-COVID designated Car...
HWEI SUNG LING
Ing Xiang Pang

HWEI SUNG LING

and 13 more

May 15, 2020
BACKGROUND: Reports on healthcare worker antibody response to COVID-19 infection are scarce. We aim to determine the COVID-19 antibody prevalence among healthcare workers in a cardiology centre and the relationship between case definition criteria with the COVID-19 antibody result. METHODS: Convenience sampling was applied. Healthcare workers in Sarawak Heart Centre (SHC) cardiology, radiology, and emergency unit were recruited. A survey form on clinical symptoms and close contact history was distributed. HEALGEN COVID-19 IgG/IgM rapid test was performed using serum/ whole blood specimen. Staff with positive COVID-19 antibody results were referred to the infectious disease specialist for assessment. RESULTS: A total of 310 staff were screened. 220(71%) were female, and the mean age was 36±7.7 years old. 46(14.8%) staff reported having clinical symptoms at some stage from the end of January 2020 to the time of this surveillance. Number of staff who had a history of overseas travel, close contact with confirmed COVID-19 patients, or had visited places with identified COVID-19 clusters were 4(1.3%), 24(7.7%) and 24(7.7%) respectively. There were 14 staff (4.5%) with positive tests positive, 2 for IgM, and 12 for IgG. All those with positive antibody were subsequently tested negative with RT-PCR test. The history of having clinical symptoms and exposure to COVID-19 cluster area were independently associated with a positive IgG result. CONCLUSION: The application of COVID-19 antibody serology rapid tests could determine true exposure of staff to the infection and allow us to reassess existing measures of infection control within the hospital.
Multifaceted Immune Responses to African Swine Fever Virus: Implications for Vaccine...
Tao Wang
Yuan Sun

Tao Wang

and 3 more

May 15, 2020
African swine fever (ASF) is a highly contagious, often fatal viral disease caused by African swine fever virus (ASFV), leading to severe hemorrhages in domestic pigs and wild boars. In 2007, ASF was reintroduced into Europe. Since then, ASF has spread to many European and Asian countries and now becomes a major concern to the swine industry worldwide. There have been various vaccine attempts, but no commercial ASF vaccines are available so far. A key hurdle in developing a safe and effective ASF vaccine is the limited understanding of the mechanisms of immune responses to and immune protection against ASFV infection. Some vaccine candidates show promising results, but more important scientific challenges remain unsolved. Here, we provide an overview of the current knowledge in innate and adaptive immune responses elicited by ASFV infection or different kinds of vaccine candidates. Additionally, the applications and prospects of vaccine candidates are discussed. Finally, we highlight the implications of these mechanisms for rational design of ASF vaccines.
Strong binding of Leupeptin with TMPRSS2 protease may be an alternate to Camostat and...
Jaganathan Ramakrishnan
Saravanan Kandasamy

Jaganathan Ramakrishnan

and 5 more

May 15, 2020
The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (Transmembrane protease serine 2) is one of the potential targets, inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these as repurposed drugs for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation for the three molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulations shows, leupeptin and the amino acids of TMPRSS2 are very stable than the other molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 after clinical trial.
FastD: fast detection of insecticide target-site insensitive mutations and overexpres...
Longfei Chen
Kun Lang

Longfei Chen

and 8 more

May 15, 2020
Target-site insensitive mutations and overexpression of detoxification genes are two major mechanisms conferring insecticide resistance. Many molecular assays were applied to detect these two kinds of resistance genetic markers in insect populations. Unfortunately, these assays are time-consuming and have high false-positive rates. RNA-Seq data, which contains information on the variation within expressed regions of the genome and expression information of detoxification genes, provides us a valuable resource to detect resistance-associated markers. At present, there is no corresponding method at present. Here, we collected 66 reported resistance mutations of four main insecticide targets (AChE, VGSC, RyR, and nAChR) of 82 insect species. Next, we obtained 403 sequences of the four target genes and 12,665 sequences of three kinds of detoxification genes including P450, GST, and CCE. Here, we developed a Perl program, FastD, to detect insecticide target-site insensitive mutations and overexpressed detoxification genes from RNA-Seq data, and constructed a web server for FastD (http://www.insect-genome.com/fastd). FastD program was then applied to detect two kinds of resistant markers in five populations of two insects, Plutella xylostella and Aphis gossypii. Results showed that RyR mutation G4946E was detected in all P. xylostella populations, with higher frequencies in two resistant populations, ZZ (66.1%) and CHR (94.55%), than a susceptible population CHS (2.32%). CYP6a2 was overexpressed 10.82-fold in ZZ population. As to A. gossypii, nAChR mutation R81T was detected in resistant population KR with 49.85% frequency, but not in susceptible population NS. CYP6CY22 and CYP6CY13 were overexpressed 39.61- and 22.04-fold respectively in KR population. FastD is a program using RNA-Seq data to detect two types of resistance markers to estimate resistance level of insect populations. Generally, resistance level estimated by FastD were consistent with previous reports, confirming the reliability of this program in predicting population resistance at omics-level.
A framework for validating noninvasive genetic spatial capture-recapture studies for...
Samantha McFarlane
Micheline Manseau

Samantha McFarlane

and 6 more

May 15, 2020
Accurately estimating abundance is a critical component of monitoring and recovery of rare and elusive species. Spatial capture-recapture (SCR) models are an increasingly popular method for robust estimation of ecological parameters. We provide a maximum likelihood analytical framework to assess results from empirical studies to inform SCR sampling design, using both simulated and empirical data from non-invasive genetic sampling of seven boreal caribou populations (Rangifer tarandus caribou) which varied in range size and estimated population density. We use simulated population data with varying levels of clustered distributions to quantify the impact of non-independence of detections on density estimates, and empirical datasets to explore the influence of varied sampling intensity on the relative bias and precision of density estimates. Simulations revealed that clustered distributions of detections did not significantly impact relative bias or precision of density estimates. The empirical genotyping success rate was 95.1%. Empirical results indicated that reduced sampling intensity had a greater impact on density estimates in smaller ranges. The number of captures and spatial recaptures were strongly correlated with precision, but not relative bias. The best sampling designs did not differ with estimated population density but differed between large and small ranges. We provide an efficient framework implemented in R to estimate the detection parameters required when designing SCR studies. The framework can be used when designing a monitoring program to minimize effort and cost while maximizing effectiveness, which is critical for informing wildlife management and conservation.
Study protocol: Evaluation of the Allergic Rhinitis Clinical Management Pathway (AR-C...
Rachel Tan
Vicky Kritikos

Rachel Tan

and 7 more

May 15, 2020
Allergic Rhinitis (AR) is a high burden chronic respiratory disease(1-4) affecting 19% of Australians; 29% in the Australian Capital Territory(ACT), Australia. Up to 70% of people with AR self-select their medication in Australian pharmacies; with only 15% selecting optimal medication(6). The Allergic Rhinitis Clinical Management Pathway(AR-CMaP) was developed as an evidence-based AR management guide to support pharmacists to optimise AR management in the pharmacy. This paper describes the method used to investigate the implementation of AR-CMaP by evaluating the impact of AR-CMaP on AR medication management and pharmacists’ practice and identifying the challenges associated with implementing AR-CMaP. This study took a mixed methods approach. The AR-CMaP was implemented and evaluated in a cohort of pharmacies in the ACT. Prior to the implementation of AR-CMaP, baseline data were collected in the pharmacy; pharmacists completed a needs assessment and a researcher administered questionnaires to people who purchased an AR-related product. The completed needs assessments individualised the AR-CMaP training and support tools provided to each participating pharmacy. Following pharmacists training, the AR-CMaP was implemented, pharmacists completed a second needs assessment and the questionnaire to people with AR were re-administered. Pharmacists were interviewed after all data collection was completed. There is an urgent need to evaluate the AR management services in community pharmacies. This study is the first to implement and evaluate an evidence-based clinical pathway in the pharmacy setting, in real life. Important insights into the practical aspects of AR management and clinical frameworks in the community pharmacy will be identified.
Pseudo-Bartter Syndrome in Chinese Children with Cystic Fibrosis: Clinical Features a...
Yuelin Shen
xiaolei tang

Yuelin Shen

and 3 more

May 15, 2020
Objectives: To characterize the clinical and genotypic features of Cystic fibrosis-associated pseudo-Bartter syndrome (CF-PBS) in Chinese children. Methods: We recruited and characterized the clinical manifestations of 11 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation was performed to define the genotypes. Results: CF-PBS was accompanied by recurrent and/or persistent pneumonia (100%), pancreatitis (81.8%), vomit and/or diarrhea (63.6%), failure to thrive (FTT) (63.6%) and liver disease (54.5%) among our patients. The predominant organisms found in the airways was Pseudomonas aeruginosa (90.9%) and Staphylococcus aureus (81.8%). The mean concentration of blood gas and electrolytes were: PH 7.58, bicarbonate 40.8 mmol/L, sodium 126.7 mmol/L, chloride 80.0 mmol/L, and potassium 2.7 mmol/L, respectively. A high recurrence rate (54.5%) of PBS was observed despite continued electrolyte supplementation during follow up. 17 different mutations of CFTR gene were identified, and 9 of them turned out to be novel observations (c.262_266delTTATA, c.579+2insACAT, c.1210-3C>G, c.1733T>C, c.2236_2246delGAGGCGATACTinsAAAAATC, c.3635delT, c.3859delG, c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A/p.G970D was the most common mutation, with an allele frequency of 18.2%. c.1521_1523delCTT/p.F508del was the first time found with homozygous genotype in patients of Chinese origin. Conclusions: In China, CF-PBS always occurs early and repeatedly in infancy, accompanied by the high frequency of multi-system co-morbidities. Recurring in school-age patients is rare but does exist. The c.2909G>A/p.G970D is the most frequent mutation in Chinese patients with CF-PBS, showing a significant ethnic tendency of Chinese origin.
COVID-19 infection in two children with cystic fibrosis in two prevalent regions of t...
Hossein Sadeghi
Amin Saeidinia

Hossein Sadeghi

and 5 more

May 15, 2020
Cystic fibrosis (CF) is a disease with chronic lung disease that is exacerbated by viral infection. COVID-19 has caused a worldwide pandemic with high death rates. As science suggests, patients with CF would be severely affected with a high rate of morbidity, hospitalization and mortality. Our aim was to present two cases with CF in highly prevalent COVID-19 regions of the world.
Angiotensin Converting Enzyme-2 (ACE2) Receptors, Asthma and Severe COVID-19 Infectio...
Ayse Ozturk

Ayse Ozturk

May 15, 2020
To editor,Asthma is one of the most common chronic respiratory diseases in the world and it is possible that asthma-related factors may influence susceptibility to coronavirus disease (COVID-19) or infection severity. There is a great concern about the effect of asthma on COVID-19 morbidity: Centers for Disease Control and Prevention(CDC) stated that people with moderate to severe asthma may have an increased risk for COVID-19 and infection may lead to an asthma attack, pneumonia, or acute respiratory disease. However, available data is limited and there is no concrete evidence that asthma is a risk factor for COVID-19. In Zhang et al. study including 140 community-infected COVID-19 patients, asthma or other allergic diseases were not reported by any of the patients1. Although the prevalence of asthma in China was 4.2% and allergic rhinitis in Wuhan was %9.7, allergy or asthma was not detected as a risk factor for COVID-19 infection [1]. In another article from Wuhan, Li et al. reported the prevalence of asthma as 0.9% in 548 patients with COVID-19 and the asthma rate did not differ between severe and non-severe COVID-19 cases2.Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry of SARS-coronavirus 2 (SARS-CoV-2) into host cells and the virus uses the transmembrane protease serine 2 (TMPRSS2) for S protein priming3. ACE2 receptors are expressed in the heart, vessels, gut, lung, kidney, testis, and brain4 and binding of SARS-CoV-2 to ACE2 receptors markedly down-regulates ACE2 receptors which have protective biological effects on human body. With the loss of the protective effect of these receptors interstitial fibrosis, endothelial dysfunction, enhanced inflammation, oxidative stress and increased coagulation can be seen5. It is interesting to note that severity of the COVID-19 disease is associated with several conditions which may have ACE2 deficiency such as older age, male gender, hypertension, diabetes, or cardiovascular disease.There may be a link between asthma and ACE2 deficiency and based on this hypothesis Peters et al. investigated differences in ACE2 and TMPRSS2 gene expression in sputum cells of 330 asthma patients and 79 healthy controls5. Gene expression of ACE2 and TMPRSS2 was similar in asthma and health. Among asthma patients, higher expressions of ACE2 and TMPRSS2 were observed in males, African Americans, and patients with diabetes mellitus. High expression of ACE2 in the lungs facilitate the entry of corona virus into lungs and may result with down-regulation of ACE2 receptors which make these subgroups more susceptible to severe SARS-CoV-2 infection. Interestingly, use of inhaled corticosteroids was associated with lower expression of ACE2 and TMPRSS2 after adjustment for asthma severity.This is an important study giving clues about possible factors explaining the low prevalence of asthma among COVID-19 patients. Asthma itself or the use of inhaled steroids may have protective effect against SARS-CoV-2 infection. However, there are some limitations. ACE2 receptors are particularly expressed in type 2 pneumocytes which have an effective role on triggering a cascade of inflammation in the lower respiratory tract. Sputum may not reflect the amount of ACE2 receptors in the lower respiratory tract including type 2 pneumocytes. Many of the inhaler steroids have less peripheral airway deposition and so inhaler steroids might not effect ACE2 expression of type 2 pneumocytes. Although direct evidence regarding the role of ACE2 in chronic obstructive pulmonary disease (COPD) and smokers is limited, studies have shown that accumulation of inflammatory cells and the release of proinflammatory cytokines in COPD were mediated by angiotensin II in which ACE2 has an active role in degradation of angiotensin II6. There are also rat studies indicating that ACE2 deficiency may have a role in the pathogenesis and progression of COPD. It is reasonable to infer that ACE2 deficiency in COPD may have a negative effect on severity of SARS-CoV-2 infection like diabetes and hypertension. Smoking status of the patients and asthma endotypes (eosinophilic or neutrophilic, atopic, non-atopic) were not provided in Peters et al study. ACE2 and TMPRSS2 expression in sputum may be different in smokers, neutrophilic asthma, or asthma-COPD overlap (ACO) subgroups and inhaled steroids may not influence ACE2 expression in these subgroups.Asymptomatic nasal carriage of COVID-19 is more common in children, asthmatic children seems to have most likely asymptomatic COVID-19 infection .Therefore to understand the basic underlying mechanisms related with chilhood asthma and mild COVID-19 infection may help to understand the possible mechanistic links for adult asthma and severe COVID-19 infection. Sajuthi et al. used nasal airway transcriptome and network co-expression analysis to identify the cellular and transcriptional factors in COVID-19 infectivity7. They used a children cohort including 695 subjects with asthma and healthy controls between the ages of 8 and 21. They mainly focused on ACE2 and TMPRSS2 expression. Intrestingly, 43% of non-asthmatics in this study were scored as T2-high like asthmatics based on their expression profile. They found that interleukin (IL)-13 mediated T2 high inflammation had a major role in ACE2 downregulation and TMPRSS2 upregulation. The results of this study can be interpreted as T2 rich inflammation may have protective role against COVID-19 by causing ACE2 downregulation or exacerbates COVID-19 infection by causing TMPRSS2 over expression. They showed that ACE2 was expressed in secretory cells and ciliated cells while TMPRSS2 was expressed by all epithelial cell types7. Virus behavior may be different depending on ACE2 and TMPRSS2 expression variations in different part of the airways such as nasal and peripheral airways and TMPRSS2 may have more effective role in peripheral airways compared to ACE2.In conclusion, it is yet to be proved that asthma is a risk factor for COVID-19 infection. Whether there is a link between asthma and COVID-19 infection remains to be determined. The heterogeneous nature of asthma may cause interindividual variation in COVID-19 infection immunology. More clinical studies focusing ACE2 and TMPRSS2 expression in central and peripheral airways are warranted to understand the role of individual factors such as atopy, obesity and smoking habit and treatment related factors such as inhaled/systemic steroid use in different asthma groups (mild/severe, T2‐high and T2- low asthma) for the risk of COVID-19 morbidity.
Clinical, laboratory and radiological features predictive of survival outcome in seve...
Jiaxing Xie
yumei Liu

Jiaxing Xie

and 21 more

May 15, 2020
Objectives: We determined the clinical and imaging features of patients with severe COVID-19 that were associated with survival. Methods: Sixty-seven patients hospitalised with severe laboratory-confirmed COVID-19, were consecutively enrolled. Clinical data, blood measurements and chest computed tomographic (CT) scans were analyzed. Results: We compared the findings between 39 survivors and 28 non-survivors. At admission, although there were no differences in white blood cell (WBC) and platelet (PLT) counts, there was an increase of WBC, neutrophil, platelet distribution width and mean platelet volume with a marked decrease of lymphocyte, monocyte, eosinophil and PLT in non-survivor group on their last day compared to survivors (P < 0.05). Non-survivors had higher ratios of peak creatinine(P<0.05) and peak lactate dehydrogenase (LDH) (P<0.05). Compared to survivors, the incremental rate of total lesion area, ground-glass opacity (GGO) area and consolidation area on CT scans was increased in non-survivors (P<0.05).The deceleration rate of total lung volume was greater in non-survivors than survivors(P<0.05). Using the univariate survival analysis, the following were predictive of non-survival: time from admission to peak of D-dimer (D2D)<16 days , initial pro-BNP>319.0 pg/ml, peak procalcitonin (PCT) ≥0.19 ng/ml, peak creatinine>96.5 μmol/l ,peak alkaline phosphatase (ALP)>81.5 u/l, median time from admission to peak ALP<18 days, the acceleration rate of total lesional area> -11.5 cm3 /day, incremental rate of GGO area> 2.4 cm3 /day and the acceleration of consolidation area> 2.3 cm3 /day. Conclusion: Hematological counts, serum analytes and radiological indicators, the latter assessed by artificial intelligence, are robust predictors of survival outcome in COVID-19.
Effect of habitat fragmentation on genetic structure of terrestrial orchid Cymbidium...
hy liang
Xiaoguo Wang

hy liang

and 5 more

May 15, 2020
Species dispersal patterns and population genetic structure can be influenced by large geographical features and habitat fragmentation. The Qinling Mountains are a major east-west mountain range and they are also the northernmost habitat of wild Cymbidium faberi in China. However, the impact of the Qinling Mountains and habitat fragmentation in the areas on genetic variation of C. faberi at population level is still poorly understood. Here, genetic analysis of C. faberi in the Qingling Mountains was conducted based on two chloroplast DNA sequences of 271 samples in 15 locations. Hierarchical analyses of molecular variance (AMOVA) and mantel test indicated that most of the genetic variance was within populations, genetic distance between populations was correlated with the geographical distance but not strong (mantel r = 0.505, P = 0.011). Spatial analysis of molecular variance (SAMOVA) indicated that the FCT reached the maximum value at K = 2 and then decreased, which supported a two-group genetic structure. Furthermore, the Extended Bayesian Skyline Plot revealed that the estimates of effective population size of C. faberi were under demographic equilibrium in the past but an apparent decline going from approximately 1 Ma towards the present. Moreover, we found that the genetic diversity of C. faberi in fragmented landscape was lower compared to continuous ones. Therefore, we concluded that the habitat fragmentation has restricted the gene flow of C. faberi by disrupting seed dispersal. Our findings may provide helpful references for understanding how humans shape the genetic structure and the importance of conserving wild orchids.
“Don’t give up” - Heart & Lung transplantation 27 years later.
Michael Magarakis
Alejandro Macias

Michael Magarakis

and 2 more

May 15, 2020
Letter to the editor
Adult Streptococcus pyogenes pneumonia secondary to suppurative tonsillitis: a case r...
Zhiyao Bao
Wenkai Meng

Zhiyao Bao

and 3 more

May 15, 2020
We report a case of community acquired pneumonia due to Streptococcus pyogenes to remind physicians be aware of pernicious characteristics of S. pyogenes and be prepared to provide proper prevention strategies to improve prognosis.
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