title: Rhinovirus and Innate Immune Function of Airway Epithelium

text: Airway epithelial cells, which lines the respiratory mucosa is in direct contact with the environment. Airway epithelial cells are the primary target for rhinovirus and other inhaled pathogens. In response to rhinovirus infection, airway epithelial cells mount both pro-inflammatory responses and antiviral innate immune responses to clear the virus efficiently. Some of the antiviral responses include the expression of IFNs, endoplasmic reticulum stress induced unfolded protein response and autophagy. Airway epithelial cells also recruits other innate immune cells to establish antiviral state and resolve the inflammation in the lungs. In patients with chronic lung disease, these responses may be either defective or induced in excess leading to deficient clearing of virus and sustained inflammation. In this review, we will discuss the mechanisms underlying antiviral innate immunity and the dysregulation of some of these mechanisms in patients with chronic lung diseases.


title: Viral infections associated with Kawasaki disease

text: Background/Purpose Kawasaki disease (KD) is a disease of unknown cause. To investigate the infectious etiology of Kawasaki disease, we initiated a prospective case-control study to investigate possible links between common viral infections and Kawasaki disease. Methods We enrolled 226 children with KD and 226 age- and sex-matched healthy children from February 2004 to March 2010. Throat and nasopharyngeal swabs were taken for both viral isolation and polymerase chain reaction (PCR) for various viruses. Results The mean age of the 226 KD cases was 2.07 years, and the male to female ratio was 1.43 (133 boys to 93 girls). Their mean fever duration was 7.5 days with a mean peak temperature of 39.7°C. In addition to the typical symptoms of fever, neck lymphadenopathy, lip fissure and/or strawberry tongue, skin rash, nonpurulent bulbar conjunctivitis, palm/sole erythema, and induration followed by periungual desquamation, these KD cases also exhibited cough (69%), rhinorrhea (58%), and diarrhea (45%). Cases of KD had a significantly higher positive rate of viral isolation in comparison with the control group (7.5% vs. 2.2%, p = 0.02). Compared with the control group, cases of KD were more likely to have overall positive rates of viral PCR (50.4% vs. 16.4%, p < 0.001) and for various viruses including enterovirus (16.8% vs. 4.4%, p < 0.001), adenovirus (8.0% vs. 1.8%, p = 0.007), human rhinovirus (26.5% vs. 9.7%, p < 0.001), and coronavirus (7.1% vs. 0.9%, p = 0.003). Conclusion We found that some common respiratory viruses, such as adenoviruses, enteroviruses, rhinoviruses, and coronaviruses, were associated with KD cases.


title: Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China

text: To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains.


title: Ribonuclease L mediates the cell-lethal phenotype of double-stranded RNA editing enzyme ADAR1 deficiency in a human cell line

text: ADAR1 isoforms are adenosine deaminases that edit and destabilize double-stranded RNA reducing its immunostimulatory activities. Mutation of ADAR1 leads to a severe neurodevelopmental and inflammatory disease of children, Aicardi-Goutiéres syndrome. In mice, Adar1 mutations are embryonic lethal but are rescued by mutation of the Mda5 or Mavs genes, which function in IFN induction. However, the specific IFN regulated proteins responsible for the pathogenic effects of ADAR1 mutation are unknown. We show that the cell-lethal phenotype of ADAR1 deletion in human lung adenocarcinoma A549 cells is rescued by CRISPR/Cas9 mutagenesis of the RNASEL gene or by expression of the RNase L antagonist, murine coronavirus NS2 accessory protein. Our result demonstrate that ablation of RNase L activity promotes survival of ADAR1 deficient cells even in the presence of MDA5 and MAVS, suggesting that the RNase L system is the primary sensor pathway for endogenous dsRNA that leads to cell death. DOI: http://dx.doi.org/10.7554/eLife.25687.001


title: Intrathecal Humoral Immunity to Encephalitic RNA Viruses

text: The nervous system is the target for acute encephalitic viral infections, as well as a reservoir for persisting viruses. Intrathecal antibody (Ab) synthesis is well documented in humans afflicted by infections associated with neurological complications, as well as the demyelinating disease, multiple sclerosis. This review focuses on the origin, recruitment, maintenance, and biological relevance of Ab-secreting cells (ASC) found in the central nervous system (CNS) following experimental neurotropic RNA virus infections. We will summarize evidence for a highly dynamic, evolving humoral response characterized by temporal alterations in B cell subsets, proliferation, and differentiation. Overall local Ab plays a beneficial role via complement-independent control of virus replication, although cross or self-reactive Ab to CNS antigens may contribute to immune-mediated pathogenesis during some infections. Importantly, protective Ab exert anti-viral activity not only by direct neutralization, but also by binding to cell surface-expressed viral glycoproteins. Ab engagement of viral glycoproteins blocks budding and mediates intracellular signaling leading to restored homeostatic and innate functions. The sustained Ab production by local ASC, as well as chemokines and cytokines associated with ASC recruitment and retention, are highlighted as critical components of immune control.


title: Palliative Care Utilization among Patients with COVID-19 in an Underserved Population: A Single-Center Retrospective Study

text: BACKGROUND: As healthcare institutions mobilize resources to address the coronavirus disease 2019 (COVID-19) pandemic, palliative care may potentially be underutilized. It is important to assess the use of palliative care in response to the COVID-19 pandemic. METHODS: This is a retrospective single center study of patients with COVID-19 diagnosed via reverse transcriptase–polymerase chain reaction assay (RT-PCR) admitted between 3/1/2020 and 4/24/2020. An analysis of the utilization of palliative care in accordance with patient comorbidities and other characteristics was performed while considering clinical outcomes. Chi square test was used to determine associations between categorical variables while T tests were used to compare continuous variables. RESULTS: The overall mortality rate was 21.5% (n=52) and in 48% (n=25) of these patients, palliative care was not involved. Fifty nine percent (n=24) of those who had palliative consults eventually elected for comfort measures and transitioned to hospice care. Among those classified as having severe COVID-19, only 40% (n=31) had palliative care involvement. Of these patients with severe COVID-19, 68% (n=52) died. Patients who got palliative care consults were of older age, had higher rates of intubation, need for vasopressors, and death. CONCLUSION: There was a low utilization rate of palliative care in patients with COVID-19. Conscious utilization of palliative care is needed at the time of COVID-19.


title: Viral Metagenome Analysis to Guide Human Pathogen Monitoring in Environmental Samples

text: AIMS: The aim of this study was to develop and demonstrate an approach for describing the diversity of human pathogenic viruses in an environmentally isolated viral metagenome. METHODS AND RESULTS: In silico bioinformatic experiments were used to select an optimum annotation strategy for discovering human viruses in virome datasets, and applied to annotate a class B biosolids virome. Results from the in silico study indicated that less than 1% errors in virus identification could be achieved when nucleotide-based search programs (BLASTn or tBLASTx), viral genome only databases, and sequence reads greater than 200 nt were considered. Within the 51,925 annotated sequences, 94 DNA and 19 RNA sequences were identified as human viruses. Virus diversity included environmentally transmitted agents such as parechovirus, coronavirus, adenovirus, and aichi virus, as well as viruses associated with chronic human infections such as human herpes and hepatitis C viruses. CONCLUSIONS: This study provided a bioinformatic approach for identifying pathogens in a virome dataset, and demonstrated the human virus diversity in a relevant environmental sample. SIGNIFICANCE AND IMPACT OF STUDY: As the costs of next generation sequencing decrease, the pathogen diversity described by virus metagenomes will provide an unbiased guide for subsequent cell-culture and quantitative pathogen analyses, and ensures that highly enriched and relevant pathogens are not neglected in exposure and risk assessments.


title: Varicella‐like exanthem associated with COVID‐19 in an 8‐year‐old girl: A diagnostic clue?

text: It has been reported that the novel coronavirus disease (COVID‐19) may be associated with a papulovesicular skin eruption predominantly involving the trunk. We hereby present a case of COVID‐19–associated varicella‐like exanthem in an 8‐year‐old girl with mild systemic symptoms.


docid: pbpvlvlk

title: A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers

text: Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20–100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.


title: Encefalomielite acuta disseminata

text: L’encefalomielite acuta disseminata (EMAD) è una malattia infiammatoria autoimmune che coinvolge il cervello e il midollo spinale. Descritta soprattutto nel bambino, generalmente fa seguito a un episodio infettivo o a una vaccinazione, ma può essere idiopatica. La sua presentazione clinica comprende un’encefalopatia acuta associata a segni e a sintomi neurologici multifocali. La sua diagnosi si basa sulla clinica e sulla risonanza magnetica, che rivela lesioni multifocali della sostanza bianca in ipersegnale T2 mal delimitate, della stessa età, che prendono il gadolinio e possono anche riguardare il talamo e i nuclei della base. Il liquor può mostrare un’iperlinfocitosi con iperproteinorrachia e, a volte, la presenza di bande oligoclonali transitorie. La sua prognosi è piuttosto favorevole, passato l’episodio monofasico, con un trattamento specifico. È quindi fondamentale escludere fino dall’inizio le sue molte diagnosi differenziali. Il trattamento dell’EMAD, di prima scelta, consiste in boli di corticosteroidi endovenosi a forti dosi. In caso di insuccesso bisogna ricorrere agli scambi plasmatici o alle immunoglobuline endovenose. Anche se, di solito, è monofasica, possono verificarsi altri episodi che fanno allora pensare a un’EMAD multifasica. Tuttavia, in alcuni casi queste nuove poussées sono una modalità di esordio di un’autentica sclerosi multipla.


title: Viral evasion of DNA-stimulated innate immune responses

text: Cellular sensing of virus-derived nucleic acids is essential for early defenses against virus infections. In recent years, the discovery of DNA sensing proteins, including cyclic GMP–AMP synthase (cGAS) and gamma-interferon-inducible protein (IFI16), has led to understanding of how cells evoke strong innate immune responses against incoming pathogens carrying DNA genomes. The signaling stimulated by DNA sensors depends on the adaptor protein STING (stimulator of interferon genes), to enable expression of antiviral proteins, including type I interferon. To facilitate efficient infections, viruses have evolved a wide range of evasion strategies, targeting host DNA sensors, adaptor proteins and transcription factors. In this review, the current literature on virus-induced activation of the STING pathway is presented and we discuss recently identified viral evasion mechanisms targeting different steps in this antiviral pathway.


title: Prevalence and outcomes of Guillain-Barré syndrome among pediatrics in Saudi Arabia: a 10-year retrospective study

text: BACKGROUND: Guillain-Barré syndrome (GBS) is a progressive acute form of paralysis most probably secondary to an immune-mediated process. GBS among Saudis has been seldom investigated, which leaves both clinicians and researchers with scarcity in knowledge. Therefore, this study aims to assess the prevalence and clinical prognosis of GBS among pediatrics admitted with acute paralysis at a large healthcare facility in Riyadh, Saudi Arabia. METHODS: This retrospective study reviewed patients’ medical records between 2005 and 2015. Eligible cases were children (<14 years old) admitted to the hospital complaining of acute paralysis and later diagnosed with one form or variant of GBS. Pearson’s chi-square, Fisher’s exact test, and binary logistic regression were employed to analyze the collected data. RESULTS: The prevalence of GBS was 49%. The male-to-female ratio was 1.45:1. The mean ± standard deviation age was 7±3.7 years. There were 34 (69.4%) cases with progression to maximum paralysis in ≤2 weeks, while 15 (30.6%) cases occurred beyond 2 weeks. Males (n=24, 82.8%) were more likely to endure progression to maximum paralysis in ≤2 weeks after the disease onset, compared to females (n=10, 50%), P=0.014. All cases complaining of respiratory problems exhibited a progression to maximum paralysis in ≤2 weeks, compared to those with no respiratory problems, P=0.027. Residual paralysis at 60 days post disease onset was highly associated with GBS patients of age 8–14 years (n=15, 65.2%), compared to younger patients (n=8, 30.8%), P=0.016. Patients admitted in colder seasons (n=14, 63.6%) were more likely to suffer residual paralysis too, compared to those in warmer seasons (n=9, 33.3%), P=0.035. GBS cases who complained of facial weakness (n=9, 75%) and ocular abnormalities (n=10, 71.4%) were also more likely to endure residual paralysis at 60 days post disease onset, P=0.025 and P=0.03, respectively. CONCLUSION: Male gender could be a determinant of rapid progression to maximum paralysis, while the older age group in pediatrics is expected to endure residual paralysis at 60 days post disease onset. GBS can be accounted as a rare disease, especially in pediatrics, so confirmed cases should be investigated comprehensively for research purposes.


title: Prevalence and Phylogeny of Coronaviruses in Wild Birds from the Bering Strait Area (Beringia)

text: Coronaviruses (CoVs) can cause mild to severe disease in humans and animals, their host range and environmental spread seem to have been largely underestimated, and they are currently being investigated for their potential medical relevance. Infectious bronchitis virus (IBV) belongs to gamma-coronaviruses and causes a costly respiratory viral disease in chickens. The role of wild birds in the epidemiology of IBV is poorly understood. In the present study, we examined 1,002 cloacal and faecal samples collected from 26 wild bird species in the Beringia area for the presence of CoVs, and then we performed statistical and phylogenetic analyses. We detected diverse CoVs by RT-PCR in wild birds in the Beringia area. Sequence analysis showed that the detected viruses are gamma-coronaviruses related to IBV. These findings suggest that wild birds are able to carry gamma-coronaviruses asymptomatically. We concluded that CoVs are widespread among wild birds in Beringia, and their geographic spread and frequency is higher than previously realised. Thus, Avian CoV can be efficiently disseminated over large distances and could be a genetic reservoir for future emerging pathogenic CoVs. Considering the great animal health and economic impact of IBV as well as the recent emergence of novel coronaviruses such as SARS-coronavirus, it is important to investigate the role of wildlife reservoirs in CoV infection biology and epidemiology.


title: Penn Medicine Head and Neck Cancer Service Line COVID‐19 management guidelines

text: INTRODUCTION: The COVID‐19 pandemic caused by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus has altered the health care environment for the management of head and neck cancers. The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits. METHODS: Creation of consensus document. RESULTS: The process yielded a consensus statement among a wide range of practitioners involved in the management of patients with head and neck cancer in a multihospital tertiary care health system. CONCLUSIONS: These guidelines support an ethical approach for the management of head and neck cancers during the COVID‐19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature.


title: Spatially Adjusted Time-varying Reproductive Numbers: Understanding the Geographical Expansion of Urban Dengue Outbreaks

text: The basic reproductive number (R(0)) is a fundamental measure used to quantify the transmission potential of an epidemic in public health practice. However, R(0) cannot reflect the time-varying nature of an epidemic. A time-varying effective reproductive number R(t) can provide more information because it tracks the subsequent evolution of transmission. However, since it neglects individual-level geographical variations in exposure risk, R(t) may smooth out interpersonal heterogeneous transmission potential, obscure high-risk spreaders, and hence hamper the effectiveness of control measures in spatial dimension. Therefore, this study proposes a new method for quantifying spatially adjusted (time-varying) reproductive numbers that reflects spatial heterogeneity in transmission potential among individuals. This new method estimates individual-level effective reproductive numbers (R(j)) and a summarized indicator for population-level time-varying reproductive number (R(t)). Data from the five most severe dengue outbreaks in southern Taiwan from 1998–2015 were used to demonstrate the ability of the method to highlight early spreaders contributing to the geographic expansion of dengue transmission. Our results show spatial heterogeneity in the transmission potential of dengue among individuals and identify the spreaders with the highest R(j) during the epidemic period. The results also reveal that super-spreaders are usually early spreaders that locate at the edges of the epidemic foci, which means that these cases could be the drivers of the expansion of the outbreak. Therefore, our proposed method depicts a more detailed spatial-temporal dengue transmission process and identifies the significant role of the edges of the epidemic foci, which could be weak spots in disease control and prevention.


title: Multiscale Biofluidic and Nanobiotechnology Approaches for Treating Sepsis in Extracorporeal Circuits

text: Infectious diseases and their pandemics periodically attract public interests due to difficulty in treating the patients and the consequent high mortality. Sepsis caused by an imbalanced systemic inflammatory response to infection often leads to organ failure and death. The current therapeutic intervention mainly includes “the sepsis bundles,” antibiotics (antibacterial, antiviral, and antifungal), intravenous fluids for resuscitation, and surgery, which have significantly improved the clinical outcomes in past decades; however, the patients with fulminant sepsis are still in desperate need of alternative therapeutic approaches. One of the potential supportive therapies, extracorporeal blood treatment, has emerged and been developed for improving the current therapeutic efficacy. Here, I overview how the treatment of infectious diseases has been assisted with the extracorporeal adjuvant therapy and the potential utility of various nanobiotechnology and microfluidic approaches for developing new auxiliary therapeutic methods.


Emergency tracheal intubation in the COVID-19 context: is it any different? Comment on Br J Anaesth 2020, xxx


title: Resonance assignment of nsp7α from arterivirus

text: The (1)H, (15)N and (13)C resonance assignment of nsp7α, a non-structural protein of unknown function from the equine arteritis virus, is reported.


title: VP leads student affairs unit in pandemic hot spot

text: Leading a student affairs unit during a global pandemic has enough challenges. But when your institution is located in one of the nation's COVID‐19 hot spots, the challenges could seem insurmountable.


title: Viral RNA structure-based strategies to manipulate translation

text: Viruses are obligate cellular parasites that must co-opt the cellular translation machinery. Eukaryote-infecting viruses have evolved a variety of ways to manipulate the cellular translation apparatus, in many cases using elegant RNA-centered strategies. These viral RNAs can alter or control every phase of the protein-making process, are very diverse in terms of target, mechanism, and the RNA structural characteristics, and are found in a wide range of viruses. In addition, as cells often attempt to limit infection by inhibiting translation, some of these viral RNAs act to overcome the cell’s antiviral response or even take advantage of it to further viral infection. Here, we present important illustrative examples of viral RNA-based strategies to exploit the translation machinery. We briefly describe what is understood of the structure and mechanism of diverse RNA elements, the advantages conferred to the virus, and some of the key unknowns that provide motivation for further exploration.


Skin manifestations of COVID-19 resembling acute limb ischemia


title: Optimizing antibiotic selection in treating COPD exacerbations

text: Our understanding of the etiology, pathogenesis and consequences of acute exacerbations of chronic obstructive pulmonary disease (COPD) has increased substantially in the last decade. Several new lines of evidence demonstrate that bacterial isolation from sputum during acute exacerbation in many instances reflects a cause-effect relationship. Placebo-controlled antibiotic trials in exacerbations of COPD demonstrate significant clinical benefits of antibiotic treatment in moderate and severe episodes. However, in the multitude of antibiotic comparison trials, the choice of antibiotics does not appear to affect the clinical outcome, which can be explained by several methodological limitations of these trials. Recently, comparison trials with nontraditional end-points have shown differences among antibiotics in the treatment of exacerbations of COPD. Observational studies that have examined clinical outcome of exacerbations have repeatedly demonstrated certain clinical characteristics to be associated with treatment failure or early relapse. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients, reserving the broader spectrum drugs for the high risk patients. Though improved outcomes in exacerbations with antibiotic choice based on such risk stratification has not yet been demonstrated in prospective controlled trials, this approach takes into account concerns of disease heterogeneity, antibiotic resistance and judicious antibiotic use in exacerbations.


title: WHO statement- “Older people are at highest risk from COVID-19”: Should the hypothesis be corroborated or rejected?

text: Coronavirus COVID 19 has become a threat to mankind affecting millions of people worldwide. United States, Italy and Spain has the highest number of Coronavirus cases as of April 30, 2020. According to World Health Organization (WHO) statement- “Older people are at highest risk from COVID-19”. However, in contrast to the statement, some new studies and findings have come to light. And this has created confusion in our mind as to whether the hypothesis should be corroborated or rejected.


docid: dtrcahpk

title: First Discovery of Acetone Extract from Cottonseed Oil Sludge as a Novel Antiviral Agent against Plant Viruses

text: A novel acetone extract from cottonseed oil sludge was firstly discovered against plant viruses including Tobacco mosaic virus (TMV), Rice stripe virus (RSV) and Southern rice black streaked dwarf virus (SRBSDV). Gossypol and β-sitosterol separated from the acetone extract were tested for their effects on anti-TMV and analysed by nuclear magnetic resonance (NMR) assay. In vivo and field trials in different geographic distributions and different host varieties declared that this extract mixture was more efficient than the commercial agent Ningnanmycin with a broad spectrum of anti-plant-viruses activity. No phytotoxic activity was observed in the treated plants and environmental toxicology showed that this new acetone extract was environmentally friendly, indicating that this acetone extract has potential application in the control of plant virus in the future.


title: Macro and non-macro explanatory factors of Chinese hotel stock returns

text: Abstract This study investigates the link between macro and non-macro explanatory factors and Chinese hotel stock returns. Macro variables include growth rates of industrial production and imports, discount rates, yield spread and inflation rate. In addition, growth rate of total foreign tourist arrivals ( Δ TA ) was introduced as another critical macro factor that may affect Chinese hotel stock returns, considering a tremendous growth of tourism in China. Empirical results indicated that the impact of Δ TA was positive, but insignificant. Thus, Chinese hotel stock returns were more sensitive to general macro variables. Non-macro events that could significantly impact Chinese hotel stock returns encompass financial crises, natural disasters, wars, terrorist attacks, political events, and sports mega-events. Discussions and conclusions are provided to guide hospitality investors.


title: Oral administration of chestnut tannins to reduce the duration of neonatal calf diarrhea

text: BACKGROUND: Neonatal calf diarrhea is generally caused by infectious agents and is a very common disease in bovine practice, leading to substantial economic losses. Tannins are known for their astringent and anti-inflammatory properties in the gastro-enteric tract. The aim of this study was to evaluate the effect of the oral administration of chestnut tannins (Castanea sativa Mill.) in order to reduce the duration of calf neonatal diarrhea. Twenty-four Italian Friesian calves affected by neonatal diarrhea were included. The duration of the diarrheic episode (DDE) was recorded and the animals were divided into a control group (C), which received Effydral® in 2 l of warm water, and a tannin-treated group (T), which received Effydral® in 2 l of warm water plus 10 g of extract of chestnut tannins powder. A Mann-Whitney test was performed to verify differences for the DDE values between the two groups. RESULTS: The DDE was significantly higher in group C than in group T (p = 0.02), resulting in 10.1 ± 3.2 and 6.6 ± 3.8 days, respectively. CONCLUSIONS: Phytotherapic treatments for various diseases have become more common both in human and in veterinary medicine, in order to reduce the presence of antibiotic molecules in the food chain and in the environment. Administration of tannins in calves with diarrhea seemed to shorten the DDE in T by almost 4 days compared to C, suggesting an effective astringent action of chestnut tannins in the calf, as already reported in humans. The use of chestnut tannins in calves could represent an effective, low-impact treatment for neonatal diarrhea.


title: Improving the Diagnosis of Bloodstream Infections: PCR Coupled with Mass Spectrometry

text: The reference method for the diagnosis of bloodstream infections is blood culture followed by biochemical identification and antibiotic susceptibility testing of the isolated pathogen. This process requires 48 to 72 hours. The rapid administration of the most appropriate antimicrobial treatment is crucial for the survival of septic patients; therefore, a rapid method that enables diagnosis directly from analysis of a blood sample without culture is needed. A recently developed platform that couples broad-range PCR amplification of pathogen DNA with electrospray ionization mass spectrometry (PCR/ESI-MS) has the ability to identify virtually any microorganism from direct clinical specimens. To date, two clinical evaluations of the PCR/ESI-MS technology for the diagnosis of bloodstream infections from whole blood have been published. Here we discuss them and describe recent improvements that result in an enhanced sensitivity. Other commercially available assays for the molecular diagnosis of bloodstream infections from whole blood are also reviewed. The use of highly sensitive molecular diagnostic methods in combination with conventional procedures could substantially improve the management of septic patients.


title: Chapter 67 Acute Exacerbations of COPD

text: Publisher Summary There has been considerable recent interest into the causes and mechanisms of exacerbations of chronic obstructive pulmonary disease (COPD) as COPD exacerbations are an important cause of the considerable morbidity and mortality found in COPD. COPD exacerbations increase with increasing severity of COPD. Earlier descriptions of COPD exacerbations had concentrated mainly on studies of hospital admission, though most COPD exacerbations are treated in the community and not associated with hospital admission. Exacerbation frequency is an important determinant of health status in COPD and is thus one of the important outcome measures in COPD. Factors predictive of frequent exacerbations included daily cough and sputum and frequent exacerbations in the previous year. In a further prospective analysis of 504 exacerbations, where daily monitoring was performed, there was some deterioration in symptoms, though no there were significant peak expiratory flow changes. Recovery was longer in the presence of increased dyspnoea or symptoms of a common cold at exacerbation. The changes observed in lung function at exacerbation were smaller than those observed at asthmatic exacerbations. The reasons for the incomplete recovery of symptoms and lung function are not clear, but may involve inadequate treatment or persistence of the causative agent. The incomplete physiological recovery after an exacerbation could contribute to the decline in lung function with time in patients with COPD. The association of the symptoms of increased dyspnoea and of the common cold at exacerbation with a prolonged recovery suggests that viral infections may lead to more prolonged exacerbations.


title: Synthesis of Fe(3)O(4)@silica/poly(N-isopropylacrylamide) as a novel thermo-responsive system for controlled release of H(3)PMo(12)O(40) nano drug in AC magnetic field

text: In this work, a new method is introduced for synthesis of nano drug for the first time. H(3)PMo(12)O(40) and Fe(3)O(4)@SiO(2)/poly(N-isopropylacrylamide), were prepared as nano drug and magneto thermally responsive nano-carrier respectively. Then the released behavior of H(3)PMo(12)O(40) nano-drug from this thermo-responsive carrier was investigated in an AC magnetic field. When a drug particle is broken up to nanometer range, the total surface area is increased; therefore the rate of dissolution and the rate of release are increased. The as-synthesized nanostructures were characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and Fourier transform infrared spectroscopy (FT-IR). Furthermore, experimental condition which lead to the released profile of H(3)PMo(12)O(40) nano-drug from Fe(3)O(4)@SiO(2)/poly(N-isopropylacrylamide), such as strength of magnetic field (H), temperature (T), particle size of drug and content of loaded drug were tested. Increasing the strength of magnetic field, temperature and content of loaded drug, the rate of drug release was also increased.


title: Coronavirus Disease 2019 and Cardiovascular System: A Narrative Review

text: At the end of 2019, a viral pneumonia disease called coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), emerged in Wuhan, China. This novel disease rapidly spread at an alarming rate that as a result, it has now been declared pandemic by the World Health Organization. Although this infective disease is mostly characterized by respiratory tract symptoms, increasing numbers of evidence had shown considerable amounts of patients with cardiovascular involvements and these were associated with higher mortality among COVID-19 patients. Cardiac involvement as a possible late phenomenon of the viral respiratory infection is an issue that should be anticipated in patients with COVID-19. Cardiovascular manifestation in COVID-19 patients include myocardial injury (MI), arrhythmias, cardiac arrests, heart failure and coagulation abnormality, ranging from 7.2% up to 33%. The mechanism of cardiac involvement in COVID-19 patients involves direct injury to myocardial cells mediated by angiotensin-converting enzyme 2 (ACE2) receptors as suggested by some studies, while the other studies suggest that systemic inflammation causing indirect myocyte injury may also play a role. Combination of proper triage, close monitoring, and avoidance of some drugs that have cardiovascular toxicity are important in the management of cardiovascular system involvement in COVID-19 patients. The involvement of the cardiovascular system in COVID-19 patients is prevalent, variable, and debilitating. Therefore, it requires our attention and comprehensive management.


title: Epidemiological trends and the effect of airport fever screening on prevention of domestic dengue fever outbreaks in Taiwan, 1998–2007

text: Summary Objective This study aimed to examine the epidemiological trends in dengue infection and the impact of imported cases and airport fever screening on community transmission in Taiwan, a dengue non-endemic island. Methods All of the dengue case data were obtained from the surveillance system of the Taiwan Center for Disease Control and were analyzed by Pearson correlations, linear regression, and geographical information system (GIS)-based mapping. The impact of implementing airport fever screening was evaluated using the Student's t-test and two-way analysis of variance. Results A total of 10 351 dengue cases, including 7.1% of imported cases were investigated between 1998 and 2007. The majority of indigenous dengue cases (98.5%) were significantly clustered in southern Taiwan; 62.9% occurred in the metropolitan areas. The seasonality of dengue cases showed a peak from September to November. Airport fever screening was successful in identifying 45% (244/542 ; 95% confidence interval 33.1–57.8%) of imported dengue cases with fever. However, no statistical difference was found regarding the impact on community transmission when comparing the presence and absence of airport fever screening. Conclusions Our results show that airport fever screening had a positive effect on partially blocking the local transmission of imported dengue cases, while those undetected cases due to latent or asymptomatic infection would be the source of new dengue outbreaks each year.


title: Transmission dynamics and evolutionary history of 2019‐nCoV

text: To investigate the time origin, genetic diversity, and transmission dynamics of the recent 2019‐nCoV outbreak in China and beyond, a total of 32 genomes of virus strains sampled from China, Thailand, and the USA with sampling dates between 24 December 2019 and 23 January 2020 were analyzed. Phylogenetic, transmission network, and likelihood‐mapping analyses of the genome sequences were performed. On the basis of the likelihood‐mapping analysis, the increasing tree‐like signals (from 0% to 8.2%, 18.2%, and 25.4%) over time may be indicative of increasing genetic diversity of 2019‐nCoV in human hosts. We identified three phylogenetic clusters using the Bayesian inference framework and three transmission clusters using transmission network analysis, with only one cluster identified by both methods using the above genome sequences of 2019‐nCoV strains. The estimated mean evolutionary rate for 2019‐nCoV ranged from 1.7926 × 10(−3) to 1.8266 × 10(−3) substitutions per site per year. On the basis of our study, undertaking epidemiological investigations and genomic data surveillance could positively impact public health in terms of guiding prevention efforts to reduce 2019‐nCOV transmission in real‐time.


title: Inosine pranobex is safe and effective for the treatment of subjects with confirmed acute respiratory viral infections: analysis and subgroup analysis from a Phase 4, randomised, placebo-controlled, double-blind study

text: BACKGROUND: Inosine pranobex (Isoprinosine®) is an immunomodulatory drug approved in several countries for the treatment of viral infections. This study compared the efficacy and safety of inosine pranobex versus placebo in subjects with clinically diagnosed influenza-like illness, including subjects with laboratory-confirmed acute respiratory viral infections. Subgroup analyses evaluated the efficacy of inosine pranobex compared to placebo in otherwise healthy (without related ongoing disease) subjects that were less than 50 years of age and healthy subjects that were at least 50 years of age. The effect of body mass index (BMI) was evaluated in subjects less than 50 years of age. METHODS: A total of 463 subjects were randomly assigned to receive inosine pranobex (n = 231) or placebo (n = 232) in this Phase 4, randomised, double-blind, multicentre study. The primary efficacy endpoint was time to resolution of all influenza-like symptoms present at baseline to none. Safety was evaluated through analysis of adverse events, vital signs, and physical examinations. RESULTS: The difference in time to resolution of all influenza-like symptoms between treatment groups was not statistically significant but showed a faster improvement in subjects in the inosine pranobex group versus those in the placebo group - Hazard Ratio = 1.175; (95 % CI: 0.806–1.714). P-value = 0.324. In the subgroup analysis for subjects less than 50 years of age, statistically significant differences in time to resolution of influenza-like symptoms that favoured the inosine pranobex group over the placebo group were observed in those without related ongoing disease and those who were non-obese (BMI <30 kg/m(2)). The differences between the inosine pranobex and placebo groups in subjects at least 50 years of age without related ongoing disease and in subjects less than 50 years of age who were obese (BMI ≥30 kg/m(2)) were not statistically significant. Inosine pranobex was generally well tolerated, and no deaths were reported. CONCLUSIONS: The study results indicate the safety of inosine pranobex for the treatment of subjects with confirmed acute respiratory viral infections and confirm the efficacy of inosine pranobex versus placebo in healthy non-obese subjects less than 50 years of age with clinically diagnosed influenza-like illnesses. TRIAL REGISTRATION: EWO-ISO-2014/1, EudraCT 2014-001863-11; Date of registration: 29 APR 2014; Detail information web link: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001863-11/results ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1965-5) contains supplementary material, which is available to authorized users.


title: Chapter 19 The Immunophysiology of Male Reproduction

text: Abstract There is a close functional relationship between the male reproductive and immune systems. Immunological responses against sperm antigens or other elements of the reproductive tract can lead to androgen insufficiency, infertility, or chronic inflammation. Systemic or local immune activation and inflammation directly inhibit the hypothalamic-pituitary-Leydig cell axis, interfere with spermatogenic cell development, and may provoke sperm antibody formation. Traditional explanations for protection of spermatogenic cells, based on physical barriers or immune cell exclusion, are not consistent with either the organization of the reproductive tract or modern concepts of immunoregulation. Regulation of immune responses in the male reproductive tract involves immunoregulatory macrophages and lymphocytes, as well as active somatic cell suppression of antigen-specific immunity by anti-inflammatory and immunosuppressive factors, including cytokines and androgenic steroids. These restraints on antigen-specific immune mechanisms appear to be counterbalanced by enhanced innate immunity. Finally, inflammatory signaling pathways appear to play an important role in normal male reproductive function, and there is evidence that establishment of male reproduction during development is intimately linked to the maturation of the local immune environment.


docid: ikvpkhfp

title: Parallel evolution of influenza across multiple spatiotemporal scales

text: Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales. DOI: http://dx.doi.org/10.7554/eLife.26875.001


Bulges in nucleic acids


docid: quhnesbr

title: Impact of corticosteroid therapy on outcomes of persons with SARS-CoV-2, SARS-CoV, or MERS-CoV infection: a systematic review and meta-analysis

text: We performed a meta-analysis to determine safety and efficacy of corticosteroids in SARS-CoV-2, SARS-CoV, and MERS-CoV infections. We searched PubMed, Web of Science, Medline, WanFang Chinese database, and ZhiWang Chinese database using Boolean operators and search terms covering SARS-CoV-2, SARS-CoV, OR MERS-CoV AND corticosteroids to find appropriate studies. Review Manager 5.3 was used to analyze results of meta-analysis. Observational studies were analyzed for quality using the modified Newcastle–Ottawa scale and randomized clinical trials, using the Jadad scale. Subjects were divided into those with severe-only and other (severe and not severe) cohorts based on published criteria. Efficacy endpoints studied included mortality, hospitalization duration, rates of intensive care unit (ICU) admission, use of mechanical ventilation, and a composite endpoint (death, ICU admission, or mechanical ventilation). We included 11 reports including 10 cohort studies and 1 randomized clinical trial involving 5249 subjects (2003–2020). Two discussed the association of corticosteroids and virus clearing and 10 explored how corticosteroids impacted mortality, hospitalization duration, use of mechanical ventilation, and a composite endpoint. Corticosteroid use was associated with delayed virus clearing with a mean difference (MD) = 3.78 days (95% confidence Interval [CI] = 1.16, 6.41 days; I(2) = 0%). There was no significant reduction in deaths with relative Risk Ratio (RR) = 1.07 (90% CI = 0.81; 1.42; I(2) = 80%). Hospitalization duration was prolonged and use of mechanical ventilation increased. In conclusion, corticosteroid use in subjects with SARS-CoV-2, SARS-CoV, and MERS-CoV infections delayed virus clearing and did not convincingly improve survival, reduce hospitalization duration or ICU admission rate and/or use of mechanical ventilation. There were several adverse effects. Because of a preponderance of observational studies in the dataset and selection and publication biases our conclusions, especially regarding SARS-CoV-2, need confirmation in a randomized clinical trial. In the interim we suggest caution using corticosteroids in persons with COVID-19.


docid: vioqjrko

title: Issues in vaccinology: Present challenges and future directions

text: Vaccination is a principal and highly cost‐effective means of controlling infectious diseases, providing direct protection against pathogens by conferring long‐lasting immunological memory and inducing population‐level herd immunity. Despite rapid ongoing progress in vaccinology, there remain many obstacles to the development and deployment of novel or improved vaccines; these include the underlying science of how to induce and sustain appropriate protective immune responses as well as bureaucratic, logistic and socio‐political hurdles. The failure to distribute and administer existing vaccines to at‐risk communities continues to account for a large proportion of infant mortality worldwide: almost 20 million children do not have access to basic vaccines and several million still die each year as a result. While emerging epidemic or pandemic diseases pose a significant threat to global health and prosperity, there are many infectious diseases which provide a continuous or cyclical burden on healthcare systems which also need to be addressed. Gaps in knowledge of the human immune system stand in the way of developing technologies to overcome individual and pathogenic variation. The challenges in tackling infectious disease and directions that the field of preventive medicine may take to improve the current picture of global health are the focus of this review.


title: Is BCG vaccination causally related to reduced COVID‐19 mortality?

text: The ongoing severe acute respiratory sickness coronavirus 2 (SARS‐CoV‐2) pandemic has resulted in more than 3,600,000 detected cases of COVID‐19 illness and nearly 260,000 deaths worldwide as of May 6, 2020. Recently, BCG vaccination was shown to correlate with reduced COVID‐19 case fatality rates (preprint: Miller et al, 2020; preprint: Sala & Miyakawa, 2020; https://www.jsatonotes.com/2020/03/if-i-were-north-americaneuropeanaustral.html). The most recent data from publicly available resources also indicate that both COVID‐19 incidence and total deaths are strongly associated with the presence or absence of national mandatory BCG vaccination programs. As seen in Table 1, seven of eight countries with very low numbers of total deaths (< 40 per 1 million population) adopted a mandatory BCG vaccination program using one of a set of 6 separate BCG strains (Table 1). In contrast, COVID‐19 mortality was markedly higher in countries where BCG vaccination is not widely administered or is given only to high‐risk groups. COVID‐19 mortality was also higher in countries where widespread BCG vaccination was discontinued more than 20 years ago and in countries that used the BCG Denmark strain regularly or temporarily. This raises the question of whether BCG vaccination and reduced COVID‐19 mortality are causally related. An additional question is why different BCG strains may be variably associated with mortality.


title: Potential Biases in Estimating Absolute and Relative Case-Fatality Risks during Outbreaks

text: Estimating the case-fatality risk (CFR)—the probability that a person dies from an infection given that they are a case—is a high priority in epidemiologic investigation of newly emerging infectious diseases and sometimes in new outbreaks of known infectious diseases. The data available to estimate the overall CFR are often gathered for other purposes (e.g., surveillance) in challenging circumstances. We describe two forms of bias that may affect the estimation of the overall CFR—preferential ascertainment of severe cases and bias from reporting delays—and review solutions that have been proposed and implemented in past epidemics. Also of interest is the estimation of the causal impact of specific interventions (e.g., hospitalization, or hospitalization at a particular hospital) on survival, which can be estimated as a relative CFR for two or more groups. When observational data are used for this purpose, three more sources of bias may arise: confounding, survivorship bias, and selection due to preferential inclusion in surveillance datasets of those who are hospitalized and/or die. We illustrate these biases and caution against causal interpretation of differential CFR among those receiving different interventions in observational datasets. Again, we discuss ways to reduce these biases, particularly by estimating outcomes in smaller but more systematically defined cohorts ascertained before the onset of symptoms, such as those identified by forward contact tracing. Finally, we discuss the circumstances in which these biases may affect non-causal interpretation of risk factors for death among cases.


title: Effectiveness of zinc supplementation on diarrhea and average daily gain in pre-weaned dairy calves: A double-blind, block-randomized, placebo-controlled clinical trial

text: The objective of this clinical trial was to evaluate the effectiveness of zinc supplementation on diarrhea and average daily weight gain (ADG) in pre-weaned dairy calves. A total of 1,482 healthy Holstein heifer and bull calves from a large California dairy were enrolled at 24 to 48 hours of age until hutch exit at approximately 90 days of age. Calves were block-randomized by time to one of three treatments: 1) placebo, 2) zinc methionine (ZM), or 3) zinc sulfate (ZS) administered in milk once daily for 14 days. Serum total protein at enrollment and body weight at birth, treatment end, and hutch exit were measured. Fecal consistency was assessed daily for 28 days post-enrollment. For a random sample of 127 calves, serum zinc concentrations before and after treatment and a fecal antigen ELISA at diarrhea start and resolution for Escherichia coli K99, rotavirus, coronavirus, and Cryptosporidium parvum were performed. Linear regression showed that ZM-treated bull calves had 22 g increased ADG compared to placebo-treated bulls (P = 0.042). ZM-treated heifers had 9 g decreased ADG compared to placebo-treated heifers (P = 0.037), after adjusting for average birth weight. Sex-stratified models showed that high birth weight heifers treated with ZM gained more than placebo-treated heifers of the same birth weight, which suggests a dose-response effect rather than a true sex-specific effect of ZM on ADG. Cox regression showed that ZM and ZS-treated calves had a 14.7% (P = 0.015) and 13.9% (P = 0.022) reduced hazard of diarrhea, respectively, compared to placebo-treated calves. Calves supplemented for at least the first five days of diarrhea with ZM and ZS had a 21.4% (P = 0.027) and 13.0% (P = 0.040) increased hazard of cure from diarrhea, respectively, compared to placebo-treated calves. Logistic regression showed that the odds of microbiological cure at diarrhea resolution for rotavirus, C. parvum, or any single fecal pathogen was not different between treatment groups. Zinc supplementation delayed diarrhea and expedited diarrhea recovery in pre-weaned calves. Additionally, zinc improved weight gain differentially in bulls compared to heifers, indicating a research need for sex-specific dosing.


title: COVID-19: Recommendations for regional anesthesia

text: • Consider using regional anesthesia during the COVID-19 pandemic whenever possible; • The presence of COVID-19 infection is not a contraindication to performing neuraxial anesthesia. • An experienced provider should perform regional anesthesia procedures. • If possible, patient consent should be obtained verbally or digitally. • Avoiding the aerosolizing nature of general anesthesia can further protect providers and other patients.


The impacts of the novel SARS-CoV-2 outbreak on surgical oncology - A letter to the editor on “The socio-economic implications of the coronavirus and COVID-19 pandemic: A review”


title: Recommendations for local-regional anesthesia during the COVID-19 pandemic

text: Abstract Since the beginning of the COVID-19 pandemic, many questions have come up regarding safe anesthesia management of patients with the disease. Regional anesthesia, whether peripheral nerve or neuraxial, is a safe alternative for managing patients with COVID-19, by choosing modalities that mitigate pulmonary function involvement. Adopting regional anesthesia mitigates adverse effects in the post-operative period and provides safety to patients and teams, as long as there is compliance with individual protection and interpersonal transmission care measures. Respecting contra-indications and judicial use of safety techniques and norms are essential. The present manuscript aims to review the evidence available on regional anesthesia for patients with COVID-19 and offer practical recommendations for safe and efficient performance.


title: The expression and antigenicity of a truncated spike-nucleocapsid fusion protein of severe acute respiratory syndrome-associated coronavirus

text: BACKGROUND: In the absence of effective drugs, controlling SARS relies on the rapid identification of cases and appropriate management of the close contacts, or effective vaccines for SARS. Therefore, developing specific and sensitive laboratory tests for SARS as well as effective vaccines are necessary for national authorities. RESULTS: Genes encoding truncated nucleocapsid (N) and spike (S) proteins of SARSCoV were cloned into the expression vector pQE30 and fusionally expressed in Escherichia coli M15. The fusion protein was analyzed for reactivity with SARS patients' sera and with anti-sera against the two human coronaviruses HCoV 229E and HCoV OC43 by ELISA, IFA and immunoblot assays. Furthermore, to evaluate the antigen-specific humoral antibody and T-cell responses in mice, the fusion protein was injected into 6-week-old BALB/c mice and a neutralization test as well as a T-cell analysis was performed. To evaluate the antiviral efficacy of immunization, BALB/c mice were challenged intranasally with SARSCoV at day 33 post injection and viral loads were determined by fluorescent quantitative RT-PCR. Serological results showed that the diagnostic sensitivity and specificity of the truncated S-N fusion protein derived the SARS virus were > 99% (457/460) and 100.00% (650/650), respectively. Furthermore there was no cross-reactivity with other two human coronaviruses. High titers of antibodies to SRASCoV appeared in the immunized mice and the neutralization test showed that antibodies to the fusion protein could inhibit SARSCoV. The T cell proliferation showed that the fusion protein could induce an antigen-specific T-cell response. Fluorescent quantitative RT-PCR showed that BALB/c mice challenged intranasally with SARSCoV at day 33 post injection were completely protected from virus replication. CONCLUSION: The truncated S-N fusion protein is a suitable immunodiagnostic antigen and vaccine candidate.


title: A rationale and framework for seeking remote electronic or phone consent approval in endovascular stroke trials – special relevance in the COVID-19 environment and beyond

text: BACKGROUND: Enrollment in time-sensitive endovascular stroke trials can be challenging because of an inability to consent a debilitated patient. Often the legally authorized representative is not on site. Remote consent procedures in the US are inconsistent with the majority of sites shunning these approaches. The current pandemic with visitor restrictions highlights the need for enhancing these options. METHODS: Remote electronic and phone consent procedures specifically for endovascular stroke trials from two comprehensive stroke centers (CSC) are presented. An overview of the genesis of informed consent procedures in the US is also included. RESULTS: The two CSCs identified as Institution-1 and Institution-2 are large tertiary systems. Institution-1 is a non-profit university-affiliated academic medical center in rural geography. Institution-2 is an HCA hospital in an urban environment. Both serve patients through a spoke-and-hub network, have participated in multiple randomized endovascular stroke trials, and have successfully used these remote options for enrollment. A tiered approach is employed at both institutions with an emphasis on obtaining informed consent in person and resorting to alternatives methods when efforts to that are unsuccessful. A rationale for electronic and phone consent is included, followed by step-by-step illustration of the process at each institution. CONCLUSION: Two examples of remote electronic or phone consent procedures from institutions in different geographic environments and organization structures demonstrate that these options can be successfully used for enrollment in stroke trials. The current pandemic highlights the need to enhance these approaches while maintaining appropriate adherence to ethical and legal frameworks.


title: Spatial Statistics and Influencing Factors of the COVID-19 Epidemic at Both Prefecture and County Levels in Hubei Province, China

text: The coronavirus disease 2019 (COVID-19) epidemic has had a crucial influence on people’s lives and socio-economic development. An understanding of the spatiotemporal patterns and influencing factors of the COVID-19 epidemic on multiple scales could benefit the control of the outbreak. Therefore, we used spatial autocorrelation and Spearman’s rank correlation methods to investigate these two topics, respectively. The COVID-19 epidemic data reported publicly and relevant open data in Hubei province were analyzed. The results showed that (1) at both prefecture and county levels, the global spatial autocorrelation was extremely significant for the cumulative confirmed COVID-19 cases (CCC) in Hubei province from 30 January to 18 February 2020. Further, (2) at both levels, the significant hotspots and cluster/outlier areas were observed solely in Wuhan city and most of its districts/sub-cities from 30 January to 18 February 2020. (3) At the prefecture level in Hubei province, the number of CCC had a positive and extremely significant correlation (p < 0.01) with the registered population (RGP), resident population (RSP), Baidu migration index (BMI), regional gross domestic production (GDP), and total retail sales of consumer goods (TRS), respectively, from 29 January to 18 February 2020 and had a negative and significant correlation (p < 0.05) with minimum elevation (MINE) from 2 February to 18 February 2020, but no association with the land area (LA), population density (PD), maximum elevation (MAXE), mean elevation (MNE), and range of elevation (RAE) from 23 January to 18 February 2020. (4) At the county level, the number of CCC in Hubei province had a positive and extremely significant correlation (p < 0.01) with PD, RGP, RSP, GDP, and TRS, respectively, from 27 January to 18 February 2020, and was negatively associated with MINE, MAXE, MNE, and RAE, respectively, from 26 January to 18 February 2020, and negatively associated with LA from 30 January to 18 February 2020. It suggested that (1) the COVID-19 epidemics at both levels in Hubei province had evident characteristics of significant global spatial autocorrelations and significant centralized high-risk outbreaks. (2) The COVID-19 epidemics were significantly associated with the natural factors, such as LA, MAXE, MNE, and RAE, -only at the county level, not at the prefecture level, from 2 February to 18 February 2020. (3) The COVID-19 epidemics were significantly related to the socioeconomic factors, such as RGP, RSP, TRS, and GDP, at both levels from 26 January to 18 February 2020. It is desired that this study enrich our understanding of the spatiotemporal patterns and influencing factors of the COVID-19 epidemic and benefit classified prevention and control of the COVID-19 epidemic for policymakers.


title: Frontline workers sound the alarm: be always sure you’re right, then go ahead

text: Amid personal protective equipment shortage, clinicians, nurses, and other frontline workers across the world have faced threatening and/or firing for self-protection during this coronavirus disease 2019 (COVID-19) pandemic. This perspective describes the different challenges that the stressed and overworked frontline workers encounter when they raise concerns despite being right. It also highlights the importance of communication and appropriate execution upon hearing those concerns.


Patient Care Rounds in the Intensive Care Unit During COVID-19


title: Feline Coronavirus 3c Protein: A Candidate for a Virulence Marker?

text: Feline infectious peritonitis virus (FIPV) is highly virulent and responsible for the highly fatal disease feline infectious peritonitis (FIP), whereas feline enteric coronavirus (FECV) is widespread among the feline population and typically causes asymptomatic infections. Some candidates for genetic markers capable of differentiating these two pathotypes of a unique virus (feline coronavirus) have been proposed by several studies. In the present survey, in order to search for markers that can differentiate FECV and FIPV, several clones of the 3a–c, E, and M genes were sequenced from samples obtained from cats with or without FIP. All genes showed genetic diversity and suggested the presence of FCoV mutant spectrum capable of producing a virulent pathotype in an individual-specific way. In addition, all the feline coronavirus FIPV strains demonstrated a truncated 3c protein, and the 3c gene was the only observed pathotypic marker for FCoVs, showing that 3c gene is a candidate marker for the distinction between the two pathotypes when the mutant spectrum is taken into account.


title: Unraveling the Molecular Mechanism of Traditional Chinese Medicine: Formulas Against Acute Airway Viral Infections as Examples

text: Herbal medicine, including traditional Chinese medicine (TCM), is widely used worldwide. Herbs and TCM formulas contain numerous active molecules. Basically, they are a kind of cocktail therapy. Herb-drug, herb-food, herb-herb, herb-microbiome, and herb-disease interactions are complex. There is potential for both benefit and harm, so only after understanding more of their mechanisms and clinical effects can herbal medicine and TCM be helpful to users. Many pharmacologic studies have been performed to unravel the molecular mechanisms; however, basic and clinical studies of good validity are still not enough to translate experimental results into clinical understanding and to provide tough evidence for better use of herbal medicines. There are still issues regarding the conflicting pharmacologic effects, pharmacokinetics, drug interactions, adverse and clinical effects of herbal medicine and TCM. Understanding study validation, pharmacologic effects, drug interactions, indications and clinical effects, adverse effects and limitations, can all help clinicians in providing adequate suggestions to patients. At present, it would be better to use herbs and TCM formulas according to their traditional indications matching the disease pathophysiology and their molecular mechanisms. To unravel the molecular mechanisms and understand the benefits and harms of herbal medicine and TCM, there is still much work to be done.


title: Human coronavirus ocurrence in different populations of Sao Paulo: A comprehensive nine-year study using a pancoronavirus RT-PCR assay

text: Human coronaviruses (HCoVs) are considered one of the most common respiratory viruses associated with respiratory tract illnesses. An emergent human coronavirus was identified as the causal agent of an epidemic of severe acute respiratory syndrome (SARS) during 2002–2003. The severity of the disease combined with its rapid spread requires the continuous surveillance of coronaviruses in worldwide populations. Epidemiological and clinical data of HCoVs infectious in the Brazilian population are scarce and restricted to one or two groups of patients. Our study aimed to investigate retrospectively the presence of HCoVs in different populations of São Paulo presenting acute respiratory tract infections (ARIs) during the years of 2001–2010. A pancoronavirus RT-PCR was performed in this study. Coronaviruses were detected in 126 (11.5%) of 1,087 specimens. Peaks detection frequency was observed during 2002–2004 and 2008–2009, with the highest detection in 2008. The prevalence of HCoVs was higher among children with heart diseases (24.6%), patients under stem cell transplantation program (24.3%) and renal transplanted patients (20.2%). Coryza, cough and fever were the most common symptoms at presentation of positive cases and wheezing, a lower respiratory tract infection symptom was reported by 12% of the total, and 27% of high at-risk patients. HCoVs may have an important role among patients with underlying conditions and transplanted ones.


Hydrogen peroxide mouthwash


title: Prevalence and Molecular Characterization of Human Metapneumovirus in Influenza A Negative Sample in Thailand

text: BACKGROUND: Human metapneumovirus (hMPV) causes respiratory tract infection in influenza‐like illness. The role of hMPV infections in all age groups in Thailand has not yet been investigated. Thus, the objective of this study was to determine prevalence of hMPV infection in all age groups in Thailand during 2011. METHODS: A total of 1,184 nasopharyngeal washes were collected from hospitalized patients and sent to the Department of Microbiology, Siriraj Hospital, for influenza A virus detection. Real‐time polymerase chain reaction (PCR) was used to detect hMPV infection. Partially, F gene from hMPV positive samples were sequenced and used for genotyping by phylogenetic tree analysis. RESULTS: The prevalence of hMPV for all age groups was 6.3%. The highest prevalence of hMPV infection was in children aged <2 years. Of 71 hMPV‐positive patients, three (4.2%) were coinfected with respiratory syncytial virus (RSV), two with rhinovirus (2.8%), one with coronavirus (1.4%), and one with RSV and adenovirus (1.4%). Phylogenetic analysis of F gene revealed that 96.8% of hMPV detected was subgenotype B1, 1.6% was sublineage A2a, and 1.6% was A2b. Genetic variation of F gene was much conserved. CONCLUSION: We demonstrated the prevalence of hMPV subgenotype B1 circulating in Thailand during 2011.


title: Lessons for COVID-19 immunity from other coronavirus infections

text: Abstract A key goal to controlling COVID-19 is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to SARS-CoV-2 are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronaviruses, and to SARS-CoV and MERS-CoV. Here we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.


title: Influence of interferon-based drugs on immunological indices in specific prevention

text: AIM: The research aimed to study the effect of interferon (IFN)-based drugs on the behavior of immunological parameters in calves during the specific prevention of associative infections. MATERIALS AND METHODS: The object of research was 45 black motley cows and their calves from birth to 2 months of life. Serum and colostrum samples were screened for antibodies against Rotavirus, diarrhea, and coronavirus using serological methods. The testing was performed before vaccination, 40 days before calving, 20 days before calving, and before calving. Colostrum samples were taken during the first milk yield. Serum samples from calves were drawn before colostrum feeding as well as at 7, 14, and 21 days, and 1 and 2 months of age. To measure the level of immunoglobulins A, M, and G, additional serum samples were collected from calves at 25, 35, 65, and 75 days after birth. RESULTS: Giving pregnant cows, an IFN-based drug at a dose of 1 ml/kg 48 h before vaccination results in the development and accumulation of antibodies to Rotavirus, coronavirus, and viral diarrhea (VD) in the colostrum, with a titer of 7.6±0.3 log(2), 5.8±0.34 log(2), and 4.4±0.18 log(2), respectively. It indicates an increase in the antigenic activity of the multivalent vaccine. CONCLUSION: IFN-based drugs enhance the protective effect of vaccination against associative infections in the newborn calves. They stimulate a rise in the titer of antibodies to Rotavirus, coronavirus, VD, and mucosal disease complex as well as an increase in immunoglobulins A, M, and G.


title: Ascertaining the impact of public rapid transit system on spread of dengue in urban settings

text: Abstract Urbanization is an important factor contributing to the global spread of dengue in recent decades, especially in tropical regions. However, the impact of public transportation system on local spread of dengue in urban settings remains poorly understood, due to the difficulty in collecting relevant locality, transportation and disease incidence data with sufficient detail, and in suitably quantifying the combined effect of proximity and passenger flow. We quantify proximity and passenger traffic data relating to 2014–2015 dengue outbreaks in Kaohsiung, Taiwan by introducing a “Risk Associated with Metro Passengers Presence” (RAMPP), which considers the passenger traffic of stations located within a fixed radius, giving more weight to the busier and/or closer stations. In order to analyze the contagion risk associated with nearby presence of one or more Kaohsiung Rapid Transit (KRT) stations, we cluster the Li's (the fourth level administrative subdivision in Taiwan) of Kaohsiung based on their RAMPP value using the K-means algorithm. We then perform analysis of variance on distinct clusterings and detect significant differences for both years. The subsequent post hoc tests (Dunn) show that yearly incidence rate observed in the areas with highest RAMPP values is always significantly greater than that recorded with smaller RAMPP values. RAMPP takes into account of population mobility in urban settings via the use of passenger traffic information of urban transportation system, that captures the simple but important idea that large amount of passenger flow in and out of a station can dramatically increase the contagion risk of dengue in the neighborhood. Our study provides a new perspective in identifying high-risk areas for transmissions and thus enhances our understanding of how public rapid transit system contributes to disease spread in densely populated urban areas, which could be useful in the design of more effective and timely intervention and control measures for future outbreaks.


title: Malaria vaccines: high-throughput tools for antigens discovery with potential for their development

text: Malaria is a disease induced by parasites of the Plasmodium genus, which are transmitted by Anopheles mosquitoes and represents a great socio-economic burden Worldwide. Plasmodium vivax is the second species of malaria Worldwide, but it is the most prevalent in Latin America and other regions of the planet. It is currently considered that vaccines represent a cost-effective strategy for controlling transmissible diseases and could complement other malaria control measures; however, the chemical and immunological complexity of the parasite has hindered development of effective vaccines. Recent availability of several genomes of Plasmodium species, as well as bioinformatic tools are allowing the selection of large numbers of proteins and analysis of their immune potential. Herein, we review recently developed strategies for discovery of novel antigens with potential for malaria vaccine development.


title: Identifying outbreaks of Porcine Epidemic Diarrhea virus through animal movements and spatial neighborhoods

text: The spread of pathogens in swine populations is in part determined by movements of animals between farms. However, understanding additional characteristics that predict disease outbreaks and uncovering landscape factors related to between-farm spread are crucial steps toward risk mitigation. This study integrates animal movements with environmental risk factors to identify the occurrence of porcine epidemic diarrhea virus (PEDV) outbreaks. Using weekly farm-level incidence data from 332 sow farms, we applied machine-learning algorithms to quantify associations between risk factors and PEDV outbreaks with the ultimate goal of training predictive models and to identify the most important factors associated with PEDV occurrence. Our best algorithm was able to correctly predict whether an outbreak occurred during one-week periods with >80% accuracy. The most important predictors included pig movements into neighboring farms. Other important neighborhood attributes included hog density, environmental and weather factors such as vegetation, wind speed, temperature, and precipitation, and topographical features such as slope. Our neighborhood-based approach allowed us to simultaneously capture disease risks associated with long-distance animal movement as well as local spatial dynamics. The model presented here forms the foundation for near real-time disease mapping and will advance disease surveillance and control for endemic swine pathogens in the United States.


title: Challenge models to assess new therapies in chronic obstructive pulmonary disease

text: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.


title: Respiratory viruses involved in influenza‐like illness in a Greek pediatric population during the winter period of the years 2005–2008,

text: Viruses are the major cause of pediatric respiratory tract infection and yet many suspected cases of illness remain uncharacterized. This study aimed to determine the distribution of several respiratory viruses in children diagnosed as having influenza‐like illness, over the winter period of 2005–2008. Molecular assays including conventional and real time PCR protocols, were employed to screen respiratory specimens, collected by clinicians of the Influenza sentinel system and of outpatient pediatric clinics, for identification of several respiratory viruses. Of 1,272 specimens tested, 814 (64%) were positive for at least one virus and included 387 influenza viruses, 160 rhinoviruses, 155 respiratory syncytial viruses, 95 adenoviruses, 81 bocaviruses, 47 parainfluenza viruses, 44 metapneumoviruses, and 30 coronaviruses. Simultaneous presence of two or three viruses was observed in 173 of the above positive cases, 21% of which included influenza virus and rhinovirus. The majority of positive cases occurred during January and February. Influenza virus predominated in children older than 1 year old, with type B being the dominant type for the first season and subtypes A/H3N2 and A/H1N1 the following two winter seasons, respectively. Respiratory syncytial virus prevailed in children younger than 2 years old, with subtypes A and B alternating from year to year. This is the most comprehensive study of the epidemiology of respiratory viruses in Greece, indicating influenza, rhinovirus and respiratory syncytial virus as major contributors to influenza‐like illness in children. J. Med. Virol. 83:1841–1848, 2011. © 2011 Wiley‐Liss, Inc.


title: Chapter 3 Wastewater remediation via combo-technology

text: Abstract The availability of safe water has been an ongoing problem and is becoming worse with increasing urbanization and population density. Only about 30% of the fresh water total is available on earth, in groundwater and surface water, for drinking and other daily human activities as well as industrial and agricultural activities. Further, 20% of the available fresh water is not available to humans living in remote areas, 60% of fresh water cannot be captured, as it comes at inconvenient times and places (e.g., monsoons and floods), and 18% of fresh water is contaminated by human activities. Only about 2% of fresh water is available for usage. Developed countries have advanced technology for water treatment and are thus able to manage the problem of water scarcity to a large extent, but advanced technology is largely unprocurable in developing and undeveloped countries due to cost. Based on the current population growth rate, it has been estimated that over 3.5 billion people will be in a water scarcity condition by 2025. The problem has become exacerbated due to the introduction of various recalcitrant, nondegradable compounds by agricultural and industrial activities. These compounds cannot be removed completely by any current available technologies. Thus, there is an urgent need of easily procurable technology with excellent efficacy in wastewater treatment.


Does the Coronavirus (COVID-19) Pandemic Call for a New Model of Older People Care?


title: FastViromeExplorer: a pipeline for virus and phage identification and abundance profiling in metagenomics data

text: With the increase in the availability of metagenomic data generated by next generation sequencing, there is an urgent need for fast and accurate tools for identifying viruses in host-associated and environmental samples. In this paper, we developed a stand-alone pipeline called FastViromeExplorer for the detection and abundance quantification of viruses and phages in large metagenomic datasets by performing rapid searches of virus and phage sequence databases. Both simulated and real data from human microbiome and ocean environmental samples are used to validate FastViromeExplorer as a reliable tool to quickly and accurately identify viruses and their abundances in large datasets.


title: Plausible role of combination of Chlorpromazine hydrochloride and Teicoplanin against COVID-19

text: [Figure: see text] Structure of COVID-19 Virus; Plausible role of combination of Chlorpromazine hydrochloride and Teicoplanin in controlling COVID-19 replication, where Chlorpromazine hydrochloride inhibiting binding of virus to Clathrin pits and Teicoplanin inhibiting inhibiting low pH cleavage of viral spike protein


title: The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans

text: Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease.


docid: rddznfax

title: Fatal Eosinophilic Myocarditis in a Healthy 17-Year-Old Male with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2c)

text: Background: Cardiac damage is frequently referred to in patients with SARS-CoV-2, is usually diagnosed by enzyme elevations, and is generally thought to be due to underlying coronary artery disease. There are references to cardiomyopathies accompanying coronavirus, but there has been no histologic confirmation. Case report: A previously healthy 17 year male old presented in full cardiac arrest to the emergency department after a 2 day history of headache, dizziness, nausea and vomiting. Autopsy demonstrated an enlarged flabby heart with eosinophilic myocarditis. There was no interstitial pneumonia or diffuse alveolar damage. Postmortem nasopharyngeal swabs detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known to cause coronavirus disease 2019 (COVID-19). No other cause for the eosinophilic myocarditis was elucidated. Conclusion: Like other viruses, SARS-CoV-2 may be associated with fulminant myocarditis.


title: A TaqMan-probe-based multiplex real-time RT-qPCR for simultaneous detection of porcine enteric coronaviruses

text: Swine enteric coronaviruses are a group of most significant pathogens causing diarrhea in piglets with similar clinical symptoms and pathological changes. To develop a simple, rapid, accurate, and high-throughput detection method for diagnosis and differential diagnosis on swine enteric coronaviruses, specific primers and probes were designed based on the highly conserved regions of transmissible gastroenteritis virus (TGEV) N, porcine epidemic diarrhea virus (PEDV) M, porcine deltacoronavirus (PDCoV) M, and porcine enteric alphacoronavirus (PEAV) N genes respectively. A TaqMan-probe-based multiplex real-time RT-qPCR assay was developed and optimized to simultaneously detect these swine enteric coronaviruses. The results showed that the limit of detection can reach as low as 10 copies in singular real-time RT-qPCR assays and 100 copies in multiplex real-time RT-qPCR assay, with all correlation coefficients (R(2)) at above 0.99, and the amplification efficiency at between 90 and 120%. This multiplex real-time RT-qPCR assay demonstrated high sensitivity, extreme specificity, and excellent repeatability. The multiplex real-time RT-qPCR assay was then employed to detect the swine enteric coronavirus from 354 field diarrheal samples. The results manifested that TGEV and PDCoV were the main pathogens in these samples, accompanied by co-infections. This well-established multiplex real-time RT-qPCR assay provided a rapid, efficient, specific, and sensitive tool for detection of swine enteric coronaviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-019-09835-7) contains supplementary material, which is available to authorized users.


title: miRNA-36 inhibits KSHV, EBV, HSV-2 infection of cells via stifling expression of interferon induced transmembrane protein 1 (IFITM1)

text: Kaposi’s sarcoma-associated herpesvirus (KSHV) is etiologically associated with all forms of Kaposi’s sarcoma worldwide. Little is currently known about the role of microRNAs (miRNAs) in KSHV entry. We recently demonstrated that KSHV induces a plethora of host cell miRNAs during the early stages of infection. In this study, we show the ability of host cell novel miR-36 to specifically inhibit KSHV-induced expression of interferon induced transmembrane protein 1 (IFITM1) to limit virus infection of cells. Transfecting cells with miR-36 mimic specifically lowered IFITM1 expression and thereby significantly dampening KSHV infection. In contrast, inhibition of miR-36 using miR-36 inhibitor had the direct opposite effect on KSHV infection of cells, allowing enhanced viral infection of cells. The effect of miR-36 on KSHV infection of cells was at a post-binding stage of virus entry. The highlight of this work was in deciphering a common theme in the ability of miR-36 to regulate infection of closely related DNA viruses: KSHV, Epstein-Barr virus (EBV), and herpes simplexvirus-2 (HSV-2). Taken together, we report for the first time the ability of host cell miRNA to regulate internalization of KSHV, EBV, and HSV-2 in hematopoietic and endothelial cells.


title: Announcing Swine Flu and the Interpretation of Pandemic Anxiety

text: This paper discusses the ways in which 2009 novel swine‐origin influenza A (H1N1) was announced and resonated with current pandemic anxieties. In particular, the US Centers for Disease Control and Prevention (CDC) are used as a lens through which recent pandemic anxieties can be analysed and understood. This entails a closer look at the securitisation of public health and the challenges and struggles this may have caused within public health agencies. In that light, CDC' formal entanglement with global health security and its announcement of the H1N1 pandemic are interpreted, followed by an ethnographically informed focus on various people who were engaged in the H1N1 emergency response and their practices and practical struggles in the face of pandemic anxiety.


title: Helicobacter pylori VacA Suppresses Lactobacillus acidophilus-Induced Interferon Beta Signaling in Macrophages via Alterations in the Endocytic Pathway

text: Helicobacter pylori causes chronic gastritis and avoids elimination by the immune system of the infected host. The commensal bacterium Lactobacillus acidophilus has been suggested to exert beneficial effects as a supplement during H. pylori eradication therapy. In the present study, we applied whole-genome microarray analysis to compare the immune responses induced in murine bone marrow-derived macrophages (BMDMs) stimulated with L. acidophilus, H. pylori, or both bacteria in combination. While L. acidophilus induced a Th1-polarizing response characterized by high expression of interferon beta (IFN-β) and interleukin 12 (IL-12), H. pylori strongly induced the innate cytokines IL-1β and IL-1α. In BMDMs prestimulated with L. acidophilus, H. pylori blocked the expression of L. acidophilus-induced IFN-β and IL-12 and suppressed the expression of key regulators of the Rho, Rac, and Cdc42 GTPases. The inhibition of L. acidophilus-induced IFN-β was independent of H. pylori viability and the virulence factor CagPAI; however, a vacuolating cytotoxin (vacA) mutant was unable to block IFN-β. Confocal microscopy demonstrated that the addition of H. pylori to L. acidophilus-stimulated BMDMs redirects intracellular processing, leading to an accumulation of L. acidophilus in the endosomal and lysosomal compartments. Thus, our findings indicate that H. pylori inhibits the development of a strong Th1-polarizing response in BMDMs stimulated with L. acidophilus by blocking the production of IFN-β in a VacA-dependent manner. We suggest that this abrogation is caused by a redirection of the endocytotic pathway in the processing of L. acidophilus.


title: Management of uncertainty orderings through ASP

text: Abstract Traditionally, most of the proposed probabilistic models of decision under uncertainty rely on numerical measures and representations. Alternative proposals call for qualitative (non-numerical) treatment of uncertainty, based on preference relations and belief orders. The automation of both numerical and non-numerical frameworks surely represents a preliminary step in the development of inference engines of intelligent agents, expert systems, and decision-support tools. In this paper we exploit Answer Set Programming to formalize and reason about uncertainty expressed as belief orders. The availability of ASP-solvers supports the design of automated tools to handle such formalizations. Our proposal reveals particularly suitable whenever the domain of discernment is partial. We first illustrate how to automatically “classify”, according to the most well-known uncertainty frameworks, any given qualitative uncertainty assessment. Then, we show how to compute an enlargement of the assessment, to any other new inference target.


title: Optimizing Access to Heart Failure Care in Canada during the COVID-19 Pandemic

text: The traditional model of heart failure (HF) care in Canada, which relies upon a multi-disciplinary team and clinic based care processes, has been undermined as a result of the COVID-19 pandemic. As the pandemic continues, we will be challenged to improve or maintain the health status of those with HF by optimizing guideline-directed care despite physical distancing constraints and a reduction in the healthcare workforce. This will require development of new strategies specifically targeted at decreasing the risk of decompensation and resultant HF hospitalization. As such, we must quickly pivot to the adoption and application of novel technologies and revise usual care models, processes, and workflow. The unprecedented COVID-19 crisis has delivered the Canadian HF community a burning platform for the design and implementation of innovative approaches to support the vulnerable population we serve; born out of necessity, we now have the opportunity to explore innovative approaches that may inform the future of HF care delivery in Canada. Herein, we provide perspectives from leadership within the Canadian Heart Failure Society (CHFS) on how to optimize HF care during the COVID-19 pandemic.


Angiotensin receptor blockers for the treatment of covid-19 and its comorbidities


title: Correspondence: Importance of the validated serum biochemistry and hemogram parameters for rapid diagnosis and to prevent false negative results during COVID‐19 pandemic

text: COVID‐19 threatens millions of lives, especially elderly population and people with chronic diseases including diabetes, hypertension, cancer, and cardiovascular diseases. Rapid and effective diagnoses are vital for the isolation of infected people and starting treatment immediately to stop the spread of COVID‐19 virus. Bioinformatics techniques such as artificial intelligence should be used for collecting the hemogram and serum biochemistry data of all COVID‐19‐ infected people worldwide, even they do not show severe symptoms. These data may help find a biomarker that can be used in combination with the CT results for rapid and accurate diagnosis of COVID‐19.


title: Reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of viral hemorrhagic septicaemia virus (VHS)

text: Abstract A one step reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detection of viral hemorrhagic septicaemia virus (VHS). A set of six primers were designed, based on the G-protein sequence of the VHS virus serotypes (He, F1, 23.75, Klapmolle and Rindsholm). The assay was optimised to amplify VHS RNA by incubation at 63°C for only 1h, and required only a simple water bath or heating block to provide a constant temperature of 63°C. RT-LAMP amplification products were detected by visual inspection using SYBR Green I stain and had a ladder-like appearance when electrophoresed on an agarose gel. The detection limit of the RT-LAMP assay was found to be similar to the commonly used RT-PCR method: both methods detected VHS RNA at a dilution of 106. The assay was evaluated using clinical samples and the results indicated the suitability and simplicity of the test as a rapid, field diagnostic tool for VHS virus.


docid: qytruuif

title: The Dilemma of Renin Angiotensin System Blockers in Coronavirus Disease (Covid‐19): Insights on the Lung Fluid Handling and Gas Exchange in Heart Failure Patients


docid: tmykgbyo

title: Outcome of COVID‐19 in liver transplant recipients: A preliminary report from Northwestern Italy

text: Covid‐19 pandemic is deeply affecting transplant activity worldwide. It is unclear whether solid organ transplant recipients are at increased risk of developing severe complications and how they should be managed, also concerning immunosuppression. This is a report about the course and management of SARS‐CoV‐2 infection in liver transplant recipients from a single center in Northwestern Italy in the period March‐April 2020. Three patients who were treated at our institution are reported in detail, whereas summary data are provided for those managed at peripheral Hospitals. Presentation varied from asymptomatic to rapidly progressive respiratory failure due to bilateral interstitial pneumonia. Accordingly, treatment and changes to immunosuppression were adapted to the severity of the disease. Overall mortality was 20%, whereas Covid‐related mortality was 10%. Two cases of prolonged (>2 months) viral carriage were observed in two asymptomatic patients who contracted the infection in the early course after transplant. Besides depicting Covid‐19 course and possible treatment scenarios in liver transplant patients, these cases are discussed in relation to the changes in our practice prompted by Covid‐19 epidemic, with potential implications for other transplant programs.


title: Metagenomic sequencing with spiked primer enrichment for viral diagnostics and genomic surveillance

text: Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use.