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Extinction is inevitable in the globalized world
Aishwarya Maheshwari

Aishwarya Maheshwari

July 23, 2020
No abstract - Extinction is a natural process and every species on this planet has an expiration date except Homo sapiens because we are extending our expiry at the cost of other species (Brook and Alroy 2017, Pimm et al. 2014, Ceballos et al. 2015). In contrast, biodiversity loss is not natural but a global issue and it is not caused by the globalization, but as a result of human activities at the global level (Pimm et al. 2014, Ceballos et al. 2015). Eventually, severe biodiversity losses lead to anthropogenic die-off and extinction of naturally occurring species (Pimm et al. 2014, Ceballos et al. 2015, DeVos et al. 2014). The previous, current and future extinction rates have been estimated using a variety of measures and their estimation methodologies vary (to be between 100 to 10,000 times higher than the natural extinction rate) but they clearly demonstrate that current extinction rates are far above than the “background” rates (Brook and Alroy 2017, Pimm et al. 2014, Ceballos et al. 2015, DeVos et al. 2014, Lamkin and Miller 2016). Aggravatedly, population declines and extirpations are appearing to be more graving than species extinction and negative cascading consequences on ecosystem services (Ceballosa et al. 2020). Substantial information is available on over-exploitation of natural resources by humans in the globalization perspective (Ceballosa et al. 2020, Millennium Ecosystem Assessment, 2005, Groom et al. 2006, Ehrnfeld 2003) and we have lost an estimated US$ 4-20 trillion per year in ecosystem services owing to land-cover change and US$ 6-11 trillion per year from land degradation during 1997 to 2011 (OECD 2019). Such loss also leads to an increased disease risk (Gilbert 2010) and recent coronavirus pandemic (COVID-19) might be one of the similar consequences.
Nature, culture and human occupation of Planet Earth
Alessandro Mondanaro
Marina Melchionna

Alessandro Mondanaro

and 16 more

July 23, 2020
Homo sapiens is possibly the most ecologically plastic animal species ever, capable to overcome climatic variability beyond its physiological limits by means of culture. This adaptability has a strong cultural component which required the development both new technologies and major social changes sometimes in our distant past1,2. Highly contentious archaeological evidence suggests these innovations may have predated the emergence of our own species3. Here we studied climate niche width evolution in Homo, using fine-detailed palaeoclimatic data while controlling for phylogenetic effects. Our results point to sudden widening of the climatic niches exploited by Homo starting with the emergence of H. heidelbergensis. From the Middle Pleistocene, Homo ceased to be confined to physiologically suitable regions, despite progressive harshening of global climatic conditions. These results suggest cultural modernity, and its associated technological advancements, including habitual use of fire and clothing, appeared before the emergence of our own species.
Stability of African swine fever virus in soil and options to mitigate the potential...
Jolene Carlson
Melina Fischer

Jolene Carlson

and 7 more

July 23, 2020
Understanding African swine fever virus (ASFV) transmission in a population is essential for strategies to minimize virus spread during an outbreak. ASFV can survive for extended periods of time in animal products, carcasses, and the environment. Recent studies have shown that wild boar demonstrate interest in carcasses at an advanced stage of decay and in the soil where the remains of wild boar once were. While ASFV nucleic acids have been found in the environment around infected farms, data on the survival of the virus in soil are scarce. We investigated different soil matrices spiked with ASFV-positive blood from infected wild boar to see if ASFV can remain viable in the soil beneath infected carcasses. Moreover, we tried different mitigation strategies that could be used in affected regions. As expected, ASFV genome detection was reliably possible over the full range of sampling days. Soil pH, structure, and ambient temperature played a significant role for the stability of infectious ASFV. Infectious ASFV was demonstrated in specimens originating from sterile sand for at least three weeks, and from ordinary beach sand for up to two weeks. In yard soil, infectious ASFV was demonstrated for one week, and in soil from a swampy area for three days. Virus was not recovered from two acidic forest soils. All risk mitigation experiments with citric acid or calcium hydroxide resulted in complete inactivation in our experimental setup. In conclusion, stability of infectious ASFV is almost non-existent in forest soils but rather high in sandy soils. However, given the high variability, treatment of carcass collection points with disinfectants should be considered for additional risk reduction. In this respect, biocidal nature and occupational safety have to be considered.
Lactobacillus fermentum CECT5716 ameliorates high fat diet-induced obesity in mice th...
Jose Alberto  Molina-Tijeras
Patricia Diez-Echave

Jose Alberto Molina-Tijeras

and 14 more

July 23, 2020
Background and Purpose: Obesity is a complex condition where a low-grade chronic inflammation and gut dysbiosis contribute to the development of the related metabolic dysfunctions. Nowadays, its management of such disease implies drastic changes in lifestyle and different anti-obesity drugs. Unfortunately, most of them present limited effectiveness and important side effects. Therefore there is an urgent demand for more effective and safer strategies for obesity management. In this sense, probiotics are emerging as a promising therapy. Different probiotics have demonstrated beneficial effects on this condition, increasing the interest in the development of probiotic treatments. Lactobacillus fermentum CECT5716 has shown anti-inflammatory effects and capacity to modulate microbiota composition in different experimental models. Experimental Approach: L. fermentum CECT5716 (5x108 CFU/mice/day) was evaluated in a model of high fat diet-induced obesity in mice. Key results: L. fermentum exerts anti-obesity effects, associated with its anti-inflammatory properties and amelioration endothelial dysfunction and gut dysbiosis. The probiotic restores Akkermansia sp. abundance and reduced Erysipelotrichi class and Clostridium spp presence as well as increased Bacteroides proportion. Conclusion and Implications: This probiotic represents a very interesting approach. Our findings describe, for the first time, the ability of this probiotic to ameliorate experimental obesity through microbiome modulation, affecting different bacteria that have been reported to play a key role in the pathogenesis of obesity. Therefore, this suggests a potential use of L. fermentum CECT5716 in clinical practice, also taking into account that probiotic treatments have demonstrated to be relatively safe and well tolerated.
Effects of Upper Limb Ischemia-Reperfusion on Regional Oxidative Stress During Aortic...
EDA BALCI
Aslı Demir

EDA BALCI

and 7 more

July 23, 2020
INTRODUCTION: The aim of this study is to evaluate the effect of acute, iatrogenic right arm ischemia and reperfusion on microcirculation using tissue perfusion markers like central venous oxygen saturation, lactate, the difference between central venous and arterial CO2 pressure, Near-infrared spectroscopy, and biomarkers like sialic acid, malondialdehyde, advanced oxidative protein products in aortic surgery with moderate hypothermia. METHODS: Adult patients undergoing ascending aorta repair with antegrade cerebral perfusion via axillary artery participated in the study. Blood samples were collected from the radial artery, internal juguler vein, right arm cubital vein and left arm cubital vein and analysis were performed at five intraoperative time points. Blood samples for biomarkers were obtained at three intraoperative time points. RESULTS: Right arm venous oxygen saturation are significantly lower than left arm and central venous. Right arm lactate levels are significantly higher than left arm and central venous lactate levels. Somatic right arm near-infrared spectroscopy values are significantly lower than somatic left arm. There are no significant differences for biomarkers throughout the time points. CONCLUSIONS: We have concluded that well-known markers such as central venous oxygen saturation and lactate reflect the results of ischemia-reperfusion faster, and are more valuable than novel biomarkers. Near-infrared spectroscopy is a promising monitor in terms of providing information about tissue oxygenation. However, oxidative stress biomarkers seem to be far from following the results of ischemia-reperfusion damage in an instant or short time, moreover, their costs are high and laboratory studies take time.
Transcatheter Mitral Valve-in-Valve-in-Valve Implantation: Implications of complex in...
Sankalp Sehgal
Pritha Subramanyam

Sankalp Sehgal

and 4 more

July 23, 2020
Paravalvular leak (PVL) after mitral valve replacement is the most common type of nonstructural prosthetic valve dysfunction. While most patients with only mild-moderate PVL are asymptomatic, those with severe PVL can present with heart failure and hemolysis, leading to significant morbidity and mortality. Surgical correction has remained the gold standard therapy for symptomatic PVL; however, for high surgical risk patients, percutaneous approaches have emerged as an alternative management. With the emergence of transcatheter mitral valve-in-valve techniques for failed bioprosthesis and rings, valve-in-valve PVL is being encountered more frequently and is identified as a challenging entity. We present a case of a symptomatic patient with a moderate – severe valve-in-valve PVL after two mitral valve replacements who then underwent a transcatheter mitral valve-in-valve-in-valve implantation with a 29mm Edwards® SAPIEN3 valve via transseptal approach. This unique case highlights the complexity of this clinical entity and recognizes three-dimensional transesophageal echocardiography as a tool to guide valve-in-valve PVL closures.
Constrictive Pericarditis and Tuberculosis: Is It Worth More Attention?
Dong Wang
Xue Sun

Dong Wang

and 2 more

July 23, 2020
Constrictive pericarditis (CP) characterized by the presence of a thick, fibrotic and/or calcified non-compliant pericardium limits diastolic filling and forces one side of the heart to fill at the expense of the other side. CP results in right heart failure and even reconstruction of the heart, especially for CP caused by tuberculosis (TB). As the leading cause of CP, TB is affecting the management of CP from many aspects, which contributes to high morbidity and mortality. The purpose of this manuscript is to: (1)Review the etiology, epidemiology, pathophysiology, diagnosis, treatment of tuberculosis constrictive pericarditis (TBCP); (2)Review animal models for CP or pericarditis through different methods; (3)Remind us that more research should be done for TBCP.
Epiphytic fungal communities vary by substrate type and at sub-meter spatial scales
Kel Cook
Jyotsna Sharma

Kel Cook

and 4 more

July 23, 2020
Fungal species have numerous important functions in the environment. Where these functions occur will depend on how fungi are spatially distributed, but spatial structures of fungal communities are largely unknown. This is especially true in hyperdiverse tropical tree canopy systems, which are understudied using high-throughput sequencing technology. Here we explore fungal communities in a Costa Rican tropical rainforest canopy, with a focus on local-scale spatial structure and substrate specificity of fungi. We sampled 135 locations across five tree branches and identified fungi from four substrate types: outer host tree bark, inner bark, dead bryophyte tissue, and living bryophytes. Samples were located between one centimeter and eight meters apart. Fungal community composition and diversity varied among substrate types, even when multiple substrates were in direct contact. Fungi were most diverse in living bryophytes, with 39% of all fungal OTUs found exclusively in this substrate, and the least diverse in inner bark. Fungal communities had significant positive spatial autocorrelation and distance decay of similarity only at distances less than one meter. Similarity among samples declines by half in less than ten centimeters, and even at these short distances, similarities are low with few OTUs shared among samples. These results indicate that community turnover is high and occurs at very small spatial scales, with any two locations sharing very few fungi in common. High heterogeneity of fungal communities in space and among substrates may have important implications for the distributions, population dynamics, and diversity of other tree canopy organisms, including epiphytic plants.
The Impact of Levothyroxine in Women with Positive Thyroid Antibodies on Pregnancy Ou...
Lorraine Lau
Jamie Benham

Lorraine Lau

and 4 more

July 23, 2020
Background: Thyroid autoimmunity in pregnant women has been associated with negative outcomes. Objective: To evaluate the effect of levothyroxine therapy on pregnancy outcomes compared with placebo or no treatment in women without overt hypothyroidism who are TPOAb and/or TgAb-positive. Search Strategy: Ovid MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched from 1980 to April 17, 2019. Selection Criteria: Pre-specified criteria for inclusion were: randomized trials of levothyroxine versus control (placebo or no treatment) among women with positive TPOAb or TgAb who were pregnant or considering conception. Data Collection and Analysis: Pre-specified data elements were extracted and where appropriate, meta-analyses were conducted. Main outcomes include pregnancy achieved, miscarriage, preterm delivery and live birth. Main Results: From 2,812 citations, 79 citations were identified for full text review. Of these, six trials (total of 2,263 women) were included for qualitative and quantitative analyses. Risk of bias was deemed low for only one trial. There was no significant difference in the relative risk (RR) of pregnancy achieved (RR 1.03; 95% CI 0.93, 1.13), miscarriage (RR 0.93; 95% CI 0.76, 1.14), preterm delivery (RR 0.66; 95% CI 0.39, 1.10), or live births (RR 1.01; 95% CI 0.89, 1.16) in thyroid autoimmune women treated with levothyroxine compared to controls. Conclusion: Among pregnant women or women planning conception, with thyroid autoimmunity, there is a lack of evidence of benefit for levothyroxine use. Recommendations to use levothyroxine in this setting need to be reconsidered.
Stabilization of the [cyclo-N5]- anion by Lewis acid-base interactions
Peng Wang
Panpan Wu

Peng Wang

and 3 more

July 23, 2020
Due to it is potential application in the field of high energy density materials, how to stabilize cyclopentazolate anion (cyclo-N5-) has attracted many interests theoretically and experimentally. Therefore, a series of ion salts containing [cyclo-N5]- were synthesized and studied. The instability of [cyclo-N5]- is caused by the five lone pairs of electrons localized on five neighbored N atoms. In this work, we expect if the [cyclo-N5]- can be stabilized by the coordination with acidic ligands, by weakening the multi repulsion from the lone pairs to stabilize the [cyclo-N5]-. The two compounds of [N5(BH3)5]-, and [N5(AgCN)5]- have been designed and compared based on the Lewis acid-base theory. [N5(H2O)5]- is designed to evaluate the effect of hydrogen bond in the stabilization. For all the structures, we study the bonding properties and thermal stabilities based on the analysis of electronic structures and Car-Parrinello molecular dynamics (CPMD) simulations. The results indicate it is a effective method to stabilize [cyclo-N5]- by introducing the Lewis acid. Our insights on [cyclo-N5]- compounds with high thermal stability under ambient conditions will provide a new idea for the research and synthesis of new high energetic [cyclo-N5]- series compounds.
Insight on the Pro-oxidant Capability of Amphotericin B in Lipid Media: A Theoretical...
Manuel E. Medina
Thuluz Meza-Menchaca

Manuel E. Medina

and 2 more

July 23, 2020
A study of the pro-oxidant capacity of amphotericin B was carried out by analyzing the photosensitizing ability of an amphotericin B model. Although amphotericin B is a well-known broad-spectrum antibiotic, little is known about the mechanism of its pro-oxidant capability. This study employed density functional theory to assess the photosensitizing capacity of AMP. Furthermore, electron transfer reactions were modeled according to the Marcus theory, considering that lipid media can mimic the environment of the cell membrane. The results show that AMP is a pro-oxidant molecule mainly through the type II mechanism, with the corresponding production of 1O2. In this way, AMP could induce oxidative stress because it is capable of generating reactive oxygen species. In this case, AMP showed a reaction rate constants of 8.94 x 109 and 1.89 x 1010 M−1 s−1 for the type I and II mechanisms, respectively, while the overall reaction rate constant was 2.79 x 1010 M−1 s−1. Therefore, the results of this study support the pro-oxidant capacity of amphotericin B in lipid media, and considering that ergosterol is more susceptible to undergoing oxidative damage by reactive oxygen species than cholesterol, this mechanism could contribute to the antifungal activity of amphotericin B.
Changes of ocular surface CD14 and TLR- 4 and TLR-9 in patients with Vernal keratocon...
marta sacchetti
Marcella Nebbioso

marta sacchetti

and 6 more

July 23, 2020
Background: CD14 is involved in the modulation of immune reaction via toll-like receptors (TLR) and may influence the development of allergic diseases. The role of CD14 in vernal keratoconjunctivitis (VKC) has not yet been investigated. The aim of this study is to evaluate changes of tear soluble sCD14 and conjunctival CD14, TLR-4 and 9 expression in patients with VKC in the active and quiescent phases. Methods: 18 patients with VKC during active inflammation (group A, N=9), in the quiescent phase (group Q, N=5) and after recovery (group R, N=4) and 10 healthy subjects were included. Patients in group A were treated with corticosteroid eye drops 4 times daily for 7 days. Expression of sCD14 in tears and of CD14, TLR-4, and TLR-9 by conjunctival epithelium were evaluated by Western Blot in all groups and after corticosteroid treatment. Results: expression of sCD14 and of CD14, TLR-4 and TLR-9 was significantly decreased in group A when compared with healthy subjects and with VKC group Q and R. Lower expression of sCD14, CD14, TLR-4 and TLR-9 were significantly correlated with the severity of papillary reaction, while the lower sCD14 was correlated with severity of conjunctival hyperemia. Conjunctival expression of TLR-4, but not sCD14, CD14 and TLR-9, was significantly reduced after topical corticosteroid treatment. Conclusion: tear sCD14, and conjunctival CD14, TLR4 and TLR-9 decreased during ocular surface inflammatory reaction in patients with VKC. CD14 and TLRs may represent potential therapeutic targets, although it requires further studies.
Large scale, complex biobanking of biofluids for immunology research and testing
Rohit Gupta
Vanitha Sampath

Rohit Gupta

and 3 more

July 23, 2020
Large scale, complex biobanking of biofluids for immunology research and testingRohit K. Gupta1, Vanitha Sampath2, Kari C. Nadeau2, Holden T. Maecker3,1 Biospecimen Resource Program, Office of Research, University of California, San Francisco, CA, USA.2 Sean N. Parker Center for Allergy and Asthma Research at Stanford University and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.3 Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.Corresponding Author: Prof. Holden Maecker, Department of Microbiology and Immunology, Fairchild Science Building, room D039, 299 Campus Drive, Stanford, CA 94305-5124, USA, Email: maecker@stanford.edu, Phone: (650) 723-1671Funding: Sean N. Parker Center for Allergy and Asthma Research at Stanford University and Sunshine Foundation.Conflict of Interest: Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), Food Allergy Research & Education (FARE), End Allergies Together (EAT), Allergenis, and Ukko Pharma; Grant awardee at NIAID, National Institute of Environmental Health Sciences (NIEHS), National Heart, Lung, and Blood Institute (NHLBI), and the Environmental Protection Agency (EPA); is involved in Clinical trials with Regeneron, Genentech, AImmune Therapeutics, DBV Technologies, AnaptysBio, Adare Pharmaceuticals, and Stallergenes-Greer; Research Sponsorship by Novartis, Sanofi, Astellas, Nestle; Data and Safety Monitoring Board member at Novartis and NHLBI; Cofounded Before Brands, Alladapt, ForTra, and Iggenix; Chief Intellectual Office at FARE, Director of the World Allergy Organization (WAO) Center of Excellence at Stanford, Personal fees from Regeneron, Astrazeneca, ImmuneWorks, and Cour Pharmaceuticals; Consultant and Advisory Board Member at European Academy of Allergy and Clinical Immunology (EAACI) Research and Outreach Committee, Ukko, Before Brands, Alladapt, IgGenix, Probio, Vedanta, Centecor, Seed, Novartis, NHBLI, EPA, National Scientific Committee of Immune Tolerance Network (ITN) and NIH Programs; US patents for basophil testing, multifood immunotherapy and prevention, monoclonal antibody from plasmoblasts, and device for diagnostics. HM, RG, and VS indicate no conflict of interest.Author Contributions : All authors wrote and edited the final manuscript.Word Count: 978To the Editor:Biobanks have evolved from simple localized storage of samples in individual labs and clinics to large industrialized repositories with sophisticated sample life cycle infrastructure. By enabling collaborations between researchers working on different aspects of a disease, biobanks can bridge the gap between clinical care and research, accelerating medical care towards precision medicine. The concomitant advances in trans-omic technologies, big data analytics, and biorepositories make possible a coordinated, robust systems biology approach. Biobanks can be envisioned as a central hub responsible for compliant custodianship of specimens and associated clinical and biological data. Operationally, biobanks should strive to provide universal consent, standardized processing, cold-chain management, and quality control checks. Here, we discuss biobanks with respect to optimal utilization of biofluid derivatives, such as cells, supernatants, and genomic material, for immunology research and testing.A number of parameters need to be considered for specimen optimization and standardization based on sample type and downstream assays to be performed. Choices begin with the blood collection tubes to be used. For DNA and RNA analysis, EDTA anticoagulated blood is most common, as heparin can inhibit downstream polymerase reactions. However, at least one source suggests that citrate may provide higher quality RNA and DNA than other stabilizers.1For immunoassays, either serum or plasma can be effectively used, but there are subtle differences for some cytokine analytes.2 As such, a minimal requirement should be to use the same matrix (serum or plasma) and same anticoagulant if using plasma, for all samples to be compared in a study. For metabolome and lipidome studies, a report by Yin et al suggests EDTA plasma as the preferred matrix, since clotting in serum tubes activates additional processes, including the release of metabolites and enzymes from activated platelets.3For cellular assays such as flow cytometry, CyTOF, or single-cell RNAseq, viably cryopreserved peripheral blood mononuclear cells (PBMCs) or other cells of interest are key. Protocols for cryopreservation are readily available, but careful attention to both freezing and thawing protocols is particularly important to maintain viability and recovery. Traditionally, heparinized blood is used for Ficoll isolation of PBMCs, but other anticoagulants are generally equivalent for functionality of cryopreserved PBMC. Concomitant use of the whole blood for other purposes (e.g., stimulation or DNA isolation) may dictate the optimal anticoagulant—for example, EDTA would inhibit T cell receptor-based stimulation, but would be compatible with molecular assays). There are also variations to traditional Ficoll protocols, using Cell Preparation Tubes (CPTs) or SepMate tubes.4 These should be considered, as they can save time and labor and overcome some hurdles for standardization of the Ficoll procedure. The main drawbacks are a slight reduction in yield or increase in erythrocyte contamination. Importantly, training and protocol adherence are still important to prevent, for example, breakage of CPT from improper centrifuge holders, inadequate PBMC separation from improper spin speed, or loss of separation if CPT are shipped in very cold temperatures. Another variable to be considered is time to processing5, which is of course highly related to whether samples are shipped prior to processing (see Figure 1). This is particularly relevant to functional cellular assays. An alternative to overnight shipping and PBMC cryopreservation for functional assays is to perform on-site stimulation and stabilization of whole blood (e.g., Smart Tube Inc., http://smarttubeinc.com); however, proper monitoring of cold-chain storage is critical to ensure frozen specimens are not compromised. For example, when using the Smart Tube system, biobanks must maintain the frozen samples at -80°C, as micro-fluctuations in temperature can cause the specimens to coagulate, rendering them unusable. In any case, there are a number of potential variables that can be detrimental to downstream analysis and even reproducibility; biobanks should strive to harmonize collection, processing, and storage of samples related to biofluids.Research institutes often have multiple laboratories, each of which may be supporting various collections of human specimens. Unfortunately, most labs have employed their own data solutions to track and search for specimens, which has led to fragmented processes and inconsistent ontologies. Utilization of biospecimens that have been collected for scientific purposes continues to be problematic and may be more effective when paired with informatics tools that enable researchers to track, annotate, and interrogate.6 Biobanks should have a sample management system (SMS) which permits labs to accurately register, label (Figure 2), and track biospecimen inventory related to study participants7; in addition, the software should be configurable to align with lab workflows, while maintaining best practices for biobanking and ensuring governance can be maintained by the individual laboratory or institute. Further, for bioinventory tracking, it is critical to connect de-identified clinical attributes from electronic health records to biological assays following analysis of specimens in a central ecosystem; this enables researchers to rapidly search and request specimens for further analysis.8 To date, although many solutions have been developed to support virtual sample catalogs, most require extensive software engineering support in order to be deployed and require data to be migrated to a central database; robust and innovative solutions for identifying unused biospecimens in the life sciences are still desired.Long thought of as freezer farms, a biobank’s primary role has always been to provide proper cold-chain storage and logistics related to biospecimens. While much literature exists on optimal storage conditions and management,9 biobanks have evolved to now facilitate research in the life sciences that extend from the physical management of the sample life cycle to supporting standardized processing, assay optimization, and modernized data infrastructure. As compliant use of biospecimens continues to be a major component being addressed through community engagement, biobanks are poised to play an important role in medical research with increasing demand for high quality biospecimens. However, a number of questions and challenges exist regarding standardization, classification, management, sustainability, as well as ethical considerations including ownership and informed consent. Ultimately, improving how biospecimens are utilized for downstream analysis can accelerate our understanding of biological mechanisms and fuel a better tomorrow.Rohit K. Gupta1Vanitha Sampath2Kari C. Nadeau2Holden T. Maecker31 Biospecimen Resource Program, Office of Research, University of California, San Francisco, CA, USA.2 Sean N. Parker Center for Allergy and Asthma Research at Stanford University and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USA.3 Institute for Immunity, Transplantation, and Infection, Stanford University, Stanford, CA, USA.
An updated review of potential therapeutic agents against COVID-19
Shahzaib Ahmad
Anum Sohail

Shahzaib Ahmad

and 2 more

July 23, 2020
Coronavirus disease of 2019 (COVID-19) is a public health emergency of international concern caused by a novel coronavirus, i.e., Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2). Since it is a new virus, an effective remedy against the virus is yet unknown. SARS-CoV-2 is a member of order nidovirales, family coronaviridae. Previously known treatment strategies against Middle East Respiratory Syndrome and Severe Acute Respiratory Syndromes are being tested for their effectiveness against SARS-CoV-2. Thus, various clinical and observational studies aimed at identifying potential therapies against the disease. In our study, we reviewed various drugs along with their mechanism of action including anti-virals, anti-bacterials, glucocorticoids, ACE inhibitors, anti retrovirals, anti-malarials, monoclonal antibodies, plasma and many more. Individual drugs are described and evaluated for their potential to treat SARS-CoV-2 infection. This study offers a brief review of the findings of trials conducted so far. Dexamethasone, convalescent plasma therapy, tocilizumab, remdesivir and combination therapies are found to be beneficial against SARS-CoV-2.
Role of desert pavements in water infiltration on fluvial fan surfaces in desert ecos...
Dejin Wang
Wenzhi Zhao

Dejin Wang

and 3 more

July 23, 2020
Desert pavements are the common features widespread in arid region, which are important for regulating the ecological and hydrologic processes. However, few studies focused on the role of water movement in maintaining ecologic function in desert pavement landscapes. This study determined the role of desert pavements in water infiltration on fluvial fans, which were reflected by characteristics of desert pavements and infiltration parameters in the middle reaches of Hexi Corridor. Six sites (i.e. one site in hill slope and other five sites in the piedmont) were selected for surveying soil properties within a 50-cm depth soil profile and measuring sorptivity (S), initial water infiltration (ii), steady-state infiltration rate (is) and infiltration time (T) in crust and scalped crust conditions under 5-cm pressure head. The results indicated that desert pavement surfaces were covered by a thin layer of protective crusts, which were primarily composed of fine earth (56.94%) and fine-medium gravel (40.46%). Although characterized by a big range of gravel coverage (19.48%- 97.63%), the crusts had small gravels (mean size: 0.58 cm) and extremely low soil moisture content (SMC; less than 1.30%), which two parameters did not significantly differ from each site in fluvial fans. The crusts were effective in restricting water infiltration capacity. When the crusts were scalped, the S, ii and is would improve 1.6, 1.7 and 1.6-fold, respectively. These three parameters significantly increased with gravel coverage and medium gravels, but significantly decreased with crust thickness and fine gravels. Desert pavements were closely with water regulation in arid systems, reflecting the vegetation distribution. This study highlights that desert pavements have a strong impact on water infiltration to function as regulating water resource and supplying water for vegetation growth.
Time trends of infant food allergy in China: three cross-sectional surveys in 1999,20...
Zhuoying Ma
Chen Lin

Zhuoying Ma

and 5 more

July 23, 2020
Background: Many countries have recorded the trends of food allergy (FA) prevalence. Little is known about epidemiological trends of childhood FA in China.Methods:In three cross-sectional surveys conducted in 1999, 2009, and 2019,the prevalence of and characteristic changes in FA in children aged ≤2 years were assessed and the outcomes were compared. All the children were recruited during well-baby check-ups at the Children's Hospital of Chongqing Medical University. All participants had a detailed medical history taken and underwent skin prick tests using ten commercial food extracts. Open food challenges were used for confirmation of FA.Results:The three studies included 1228 children (314 in 1999;401 in 2009; and 513 in 2019; response rate > 95 %).The prevalence of FA in 2009 (7.7%) and 2019 (11.1%) was significantly higher than that in 1999 (3.5%). However, there was no statistically significant difference in prevalence between 2009 and 2019 (P = 0.086). There was evidence of increased prevalence in CMPA between 1999 and 2019 (1.6% versus 5.7%;P=0.004);However, no statistic difference was found in egg allergy (2.9% versus 5.5%;P=0.21). The incidence of skin symptoms did not differ significantly over the study period, while the incidence of gastrointestinal symptoms increased significantly (18.2% in 1999, 12.9% in 2009, and 43.9% in 2019; P<0.05).Conclusions: The prevalence of FA in children rapidly increased after the 1990s and gradually stabilized after 2010. Cow’s milk has become the most common food allergen among children in Chongqing. The incidence of gastrointestinal symptoms as a manifestation of FA has increased significantly since 2010.
Single-dose dexamethasone as an adjuvant therapy for sore throat in adults: A cohort...
Dong-gon Hyun
Yoon jung Jang

Dong-gon Hyun

and 1 more

July 23, 2020
Background: Several studies have suggested that a short course of corticosteroid therapy with the standard care increases complete sore throat resolution in 24 hours, however, corticosteroids are yet to be a common prescription for acute sore throat patients. This study aimed to confirm the effectiveness and safety of adjuvant corticosteroid treatment with standard care, by investigating the treatment response and prognostic factors associated with increased symptom resolution. Methods: This retrospective study included 40 patients with acute sore throat symptoms. The degree of sore throat was checked using the manner of Numeral Rating Scale (NRS). Patients were orally or intramuscularly administered a single dose of 10 mg of dexamethasone as an adjuvant therapy with conventional treatments. Treatment response was stratified according to the degree of resolution of sore throat at 24 hours. Results: Of the 40 patients involved, 27 (67.5%) showed more than 50% reduction in NRS in 24 hours. On the contrary, 9 patients (22.5%) experienced less than 50% sore throat resolution, while 4 (10%) reported no significant pain relief. Multivariable logistic model controlling for significant covariables revealed that cough (OR, 0.02; 95% confidence interval, 0.01-0.40; p = 0.01) was an independent factor for predicting treatment response. In addition, post-hoc analysis showed a negative association between treatment response and the degree of cough (86.7% in no cough vs. 75.0% in intermittent cough vs. 47.1% in persistent cough, P = 0.023). Additionally, none of the patients experienced infection complications. Conclusions: A single-dose dexamethasone as an adjuvant therapy with standard care is an effective and safe strategy for patients presenting with acute sore throat in primary care clinics. Specifically, the efficacy of corticosteroid treatment for sore throat was higher in patients without cough.
Lumbar Puncture: Indications, Challenges and Recent advances
Biswamohan  Mishra
Venugopalan Vishnu

Biswamohan Mishra

and 1 more

July 23, 2020
Introduction The methodological, diagnostic and therapeutic aspects of lumbar puncture (LP) and CSF study have undergone many radical changes, since it was first done in 1890 by Quincke. Objectives To explore the current trends in LP practice and to suggest a safety checklist to avoid the common complications and pitfalls. To study recent advances in diagnostic and therapeutic aspects of LP and safety and efficacy of outpatient LP. We also intended to explore the common practices that are being followed peri-LP procedure, whether these are real diligences or myth only. Methods With the key words of lumbar puncture, spinal tap, and CSF examination, we searched google scholar, Embase, PubMed, Medline and Cochrane library for relevant articles, case reports, case series, consensus guidelines, expert opinions, meta- analysis, and systematic reviews. Search terms included combinations of the Medical Subject Headings “spinal puncture”, “meningitis”, “cerebrospinal fluid”, “injections, spinal”, “Trends”, “Check List”, “Outpatient”,” Complication”, “Meningeal Enhancement Post LP”, “CT prior to LP”, “Difficult LP” and “biomarkers/ cerebrospinal fluid”. Articles published between January 1990 to May 2020in English were considered and were categorised into case reports, case series, meta-analysis, systematic review. Results Common complications of lumbar puncture can be avoided if a step by step approach to rule out complications is followed, and a safety checklist is adhered to. Atraumatic LP needle better than conventional ones. Outpatient LP is safe and efficacious. Medications administered through intrathecal and intraventricular routes are ever increasing. Biomarkers in CSF will have substantial clinical implications in neurodegenerative diseases. MRI prior to LP does not cause significant meningeal enhancement and the practice of delaying LP for imaging in every case should not be encouraged. Conclusions LP has evolved from being primarily a tool to diagnose CSF infections, to diagnosing, and treating major CNS autoimmune, neuroinflammatory and neurodegenerative and congenital diseases.
Cardiovascular risks in active athletes within the provincial directorate of youth an...
HASAN SAKALLI
Celal Kus

HASAN SAKALLI

and 5 more

July 23, 2020
Background: The place of sport is indisputable for a healthy society. This study aimed to assess the health risks of athletes engaged in sports activities in various branches in the Youth Center operating. Methods: In this cross-sectional study, data from 181 athletes were analyzed. A 20-item questionnaire including demographic information and sports history of the athletes was applied to the participants. Physical examinations were performed. Additionally, complete blood count, biochemistry, lipid profile, TSH, T4, and ECG examinations were requested from the participants. Results: In 25 (13.8%) of the participants, a pathology that could constitute a sport obstacle was detected. When the data examined concerning the presence of pathological status were compared, cardiac rate, HDL, LDL, calcium, ALT, diastolic blood pressure, the frequency of training per week, the presence of ventricular hypertrophy, t wave, and deviation in cardiac axis were statistically significant. Conclusion: The presence of conditions that may pose a risk to the health of athletes in people who are engaged in active sports suggests that some findings have been missed in the examinations for entry to sports. Family physicians should take a full anamnesis when evaluating people who want to do sports, carry out a detailed examination, and predicate their findings on laboratory findings.Keywords: General Practice, Primary Care, Risk Assessment,‎ Screening, Sports Medicine
Impact of the adjustment of stratification factors on time-to-event analyses
Madan Kundu
Shoubhik Mondal

Madan Kundu

and 1 more

July 23, 2020
In a stratified clinical trial design with time to event end points, stratification factors are often accounted for the log-rank test and the Cox regression analyses. In this work, we have evaluated the impact of inclusion of stratification factors on the power of the stratified log-rank test and have compared the bias and standard error in HR estimate between multivariate and stratified Cox regression analyses through simulation. Results from our investigation suggests that both failing to consider stratification factor in presence of their prognostic effect and stratification with smaller number of events may substantially reduce the power of the log-rank test. Further, the HR estimate from the multivariate Cox analysis is more accurate and precise compared to the stratified Cox analysis. Our findings point towards the necessity of evaluating the impact of stratification factors on the time to event analyses at the time of study design which is presently not a norm.
Efficacy and Safety of Intravenous Nicorandil on blood pressure in patients with coro...
Wang Min
He Yan

Wang Min

and 1 more

July 23, 2020
Aims The study was to investigate the effects of Intravenous Nicorandil on blood pressure and drug safety in patients with coronary heart disease. Methods In order to evaluate the blood pressure lowering effects and safety of Intravenous Nicorandil, we recruited 43 inpatients with unstable angina to intravenously pump Nicorandil, and the pumping speeds (2mg/h, 4mg/h and 6mg/h, respectively) were adjusted according to the patient’s blood pressure. After treatment, the effects of Intravenous Nicorandil on blood pressure and drug safety were observed. Results After treatment, the average reduction in SBP was 22.86±19.83mmHg,and the average reduction in DBP was 9.80±18.58mmHg. And Nicorandil could decrease patients blood pressure in a concentration-dependent manner. During the following-up, no serious adverse events were observed. Conclusion Intravenous Nicorandil could significantly reduce systolic and diastolic blood pressure in patients without affecting heart rate, and it reduced in depending on concentrations, suggesting that Intravenous Nicorandil may be a new intravenous antihypertensive drug in future clinical application.
Utilization, trust and satisfaction with health care in adult sickle cell disease pat...
Jacquelyn Baskin
Anne Nord

Jacquelyn Baskin

and 6 more

July 23, 2020
Introduction: Transition from pediatric to adult care for emerging adults with sickle cell disease (SCD) has been challenging due to limited availability of experienced adult providers and patient difficulty navigating the adult health care system. The purpose of this study was to determine among adults with SCD, healthcare utilization and their trust and satisfaction with their health care provider. Methods: We surveyed adult patients greater than 21 years old with SCD previously transitioned from Children’s Hospital Los Angeles. Assessments of provider trust and satisfaction were conducted along with health care utilization and the transition experience. Results: Of 31 participants, 61% and 68% identified having an adult primary care provider (PCP) and adult hematologist respectively. Increased satisfaction with care was associated with increased trust in the adult hematologist (r=0.72 p<0.001) and PCP (r=0.76 p=0.001) and improved communication (p< 0.001). Trust in their hematologist was greater than PCP (76.5 vs 64.2, p = 0.058). For SCD complications, 65% of participants visited the ED, 80% of whom had negative experiences including sub-optimal pain management. Regarding transition experience, 55% felt unprepared for adult care. Discussion: More than 30% of adult SCD patients transferred out of pediatric care are not receiving regular hematology care for their SCD, resulting in fragmented medical care. Increased trust in their adult hematologist and clear communication are associated with higher levels of satisfaction with care. These findings will be utilized to develop a transition program to improve patient preparation and build on partnerships with adult providers to improve long-term outcomes.
Cranial polyneuropathy as the first manifestation of a severe COVID-19 in a child
Aphaia Roussel
David Germanaud

Aphaia Roussel

and 6 more

July 23, 2020
We report a rare acute neurological complication associated with COVID-19 in a 6-year-old girl with hematopoietic stem cell transplantation (HSCT) for sickle cell anemia. 21 days after transplant she presented an acute facial diplegia, followed by a swallowing and left sensitive involvement, associated with an MRI T2 hypersignal and gadolinium enhancement of facial and hypoglossal nerves. Fever and severe respiratory symptoms appeared secondarily leading to the diagnosis of COVID-19. This cranial polyneuropathy in a child was inaugural, questioning the typical post-infectious mechanism. Physicians should consider SARS-CoV-2 in patients with cranial nerve abnormalities even without respiratory manifestations or fever.
Impact of the COVID-19 pandemic in Radiopharmacy Activities: Preliminary report: firs...
Fatma Al-Saeedi

Fatma Al-Saeedi

July 23, 2020
Rationale, aims, and objectives: The coronavirus pandemic has disrupted normal activities across the world, from economy to socialization, and claiming hundreds of thousands of lives. The activities in radiopharmacy laboratories across the globe have been affected significantly. This survey was conducted to assess the effect of COVID-19 on radiopharmacy and activities going on in the laboratories around the world. This was meant to undertake a preliminary record of the continuing survey. Methods: A three-sectioned questionnaire with 12 questions was distributed to the professional working on radiopharmacy laboratories. The sections included demographic information, the effect of the pandemic on the regular operation on a radiopharmacy, and the measures taken to prevent the spread of the virus among the laboratory staff. Random sampling approach was used to select 100 respondents, including staff and radiochemists, across different parts of the world. Results: The survey demonstrated that the pandemic hugely impacted activities in a radiopharmacy laboratory. 98% of the respondents reported major disruptions in the normal schedule in the laboratory. Even though some laboratories continued working normally, strict measures were put in place to prevent the spread of the virus among the staff. In many radiopharmacy laboratories, diagnostic procedures and tests quantitatively decreased. The survey reported positron emission radiopharmaceutical fluorodeoxyglucose F-18 (F18-FDG) as the frequently organ imaging radiopharmaceutical during the pandemic. Conclusions: The survey showed that COVID-19 has negatively impacted activities in a radiopharmacy laboratory, consequently affecting research activities.
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