title: “Alternative” Endocytic Mechanisms Exploited by Pathogens: New Avenues for Therapeutic Delivery?

text: Some pathogens utilize unique routes to enter cells that may evade the intracellular barriers encountered by the typical clathrin-mediated endocytic pathway. Retrograde transport and caveolar uptake are among the better characterized pathways, as alternatives to clathrin-mediated endocytosis, that are known to facilitate entry of pathogens and potential delivery agents. Recent characterization of the trafficking mechanisms of prion proteins and certain bacteria may present new paradigms for strategizing improvements in therapeutic spread and retention of therapy. This review will provide an overview of such endocytic pathways, and discuss current and future possibilities in using these routes as a means to improve therapeutic delivery.


title: Survivability, Partitioning, and Recovery of Enveloped Viruses in Untreated Municipal Wastewater

text: [Image: see text] Many of the devastating pandemics and outbreaks of the 20th and 21st centuries have involved enveloped viruses, including influenza, HIV, SARS, MERS, and Ebola. However, little is known about the presence and fate of enveloped viruses in municipal wastewater. Here, we compared the survival and partitioning behavior of two model enveloped viruses (MHV and ϕ6) and two nonenveloped bacteriophages (MS2 and T3) in raw wastewater samples. We showed that MHV and ϕ6 remained infective on the time scale of days. Up to 26% of the two enveloped viruses adsorbed to the solid fraction of wastewater compared to 6% of the two nonenveloped viruses. Based on this partitioning behavior, we assessed and optimized methods for recovering enveloped viruses from wastewater. Our optimized ultrafiltration method resulted in mean recoveries (±SD) of 25.1% (±3.6%) and 18.2% (±9.5%) for the enveloped MHV and ϕ6, respectively, and mean recoveries of 55.6% (±16.7%) and 85.5% (±24.5%) for the nonenveloped MS2 and T3, respectively. A maximum of 3.7% of MHV and 2% of MS2 could be recovered from the solids. These results shed light on the environmental fate of an important group of viruses and the presented methods will enable future research on enveloped viruses in water environments.


title: Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX

text: Many viruses express factors that reduce host gene expression through widespread degradation of cellular mRNA. An example of this class of proteins is the mRNA-targeting endoribonuclease SOX from the gamma-herpesvirus Kaposi’s sarcoma-associated herpesvirus (KSHV). Previous studies indicated that cleavage of messenger RNAs (mRNA) by SOX occurs at specific locations defined by the sequence of the target RNA, which is at odds with the down-regulation of a large portion of cellular transcripts. In this study, we address this paradox by using high-throughput sequencing of cleavage intermediates combined with a custom bioinformatics-based analysis pipeline to identify SOX cleavage sites across the mRNA transcriptome. These data, coupled with targeted mutagenesis, reveal that while cleavage sites are specific and reproducible, they are defined by a degenerate sequence motif containing a small number of conserved residues rather than a strong consensus sequence. This degenerate element is well represented in both human and KSHV mRNA, and its presence correlates with RNA destabilization by SOX. This represents a new endonuclease targeting strategy, in which use of a degenerate targeting element enables RNA cleavage at specific locations without restricting the range of targets. Furthermore, it shows that strong target selectivity can be achieved without a high degree of sequence specificity.


title: Unit root properties of crude oil spot and futures prices

text: Abstract In this article, we examine whether WTI and Brent crude oil spot and futures prices (at 1, 3 and 6 months to maturity) contain a unit root with one and two structural breaks, employing weekly data over the period 1991–2004. To realise this objective we employ Lagrange multiplier (LM) unit root tests with one and two endogenous structural breaks proposed by Lee and Strazicich [2003. Minimum Lagrange multiplier unit root test with two structural breaks. Review of Economics and Statistics, 85, 1082–1089; 2004. Minimum LM unit root test with one structural break. Working Paper no. 04–17, Department of Economics, Appalachian State University]. We find that each of the oil price series can be characterised as a random walk process and that the endogenous structural breaks are significant and meaningful in terms of events that have impacted on world oil markets.


title: Neurological manifestations of COVID-19: a review of what we know so far

text: Coronavirus disease 2019 (COVID‐19) has become a pandemic disease globally. While it mostly presents with respiratory symptoms, it has already been found that it could manifest with a series of neurological symptoms as well, either at presentation or during the course of the disease. Symptoms vary from non-specific such as headache or dizziness to more specific such as convulsions and cerebrovascular disease (CVD). This study aims to give an overview of the neurological manifestations of COVID-19 and discuss the potential pathogenetic mechanisms of central nervous system (CNS) involvement. Clinicians and especially internists, neurologists, and infectious disease specialists should be aware of these symptoms and able to recognize them early. Prompt diagnosis and immediate management of the neurological manifestations of the novel coronavirus will not only improve the prognosis of COVID-19 patients but will also prevent the dissemination of the disease due to misdiagnosed cases.


title: Broad and strong memory CD4+ and CD8+ T cells induced by SARS-CoV-2 in UK convalescent COVID-19 patients

text: COVID-19 is an ongoing global crisis in which the development of effective vaccines and therapeutics will depend critically on understanding the natural immunity to the virus, including the role of SARS-CoV-2-specific T cells. We have conducted a study of 42 patients following recovery from COVID-19, including 28 mild and 14 severe cases, comparing their T cell responses to those of 16 control donors. We assessed the immune memory of T cell responses using IFNγ based assays with overlapping peptides spanning SARS-CoV-2 apart from ORF1. We found the breadth, magnitude and frequency of memory T cell responses from COVID-19 were significantly higher in severe compared to mild COVID-19 cases, and this effect was most marked in response to spike, membrane, and ORF3a proteins. Total and spike-specific T cell responses correlated with the anti-Spike, anti-Receptor Binding Domain (RBD) as well as anti-Nucleoprotein (NP) endpoint antibody titre (p<0.001, <0.001 and =0.002). We identified 39 separate peptides containing CD4+ and/or CD8+ epitopes, which strikingly included six immunodominant epitope clusters targeted by T cells in many donors, including 3 clusters in spike (recognised by 29%, 24%, 18% donors), two in the membrane protein (M, 32%, 47%) and one in the nucleoprotein (Np, 35%). CD8+ responses were further defined for their HLA restriction, including B*4001-restricted T cells showing central memory and effector memory phenotype. In mild cases, higher frequencies of multi-cytokine producing M- and NP-specific CD8+ T cells than spike-specific CD8+ T cells were observed. They furthermore showed a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses. Immunodominant epitope clusters and peptides containing T cell epitopes identified in this study will provide critical tools to study the role of virus-specific T cells in control and resolution of SARS-CoV-2 infections. The identification of T cell specificity and functionality associated with milder disease, highlights the potential importance of including non-spike proteins within future COVID-19 vaccine design.


title: Viral pathogens among elderly people with acute respiratory infections in Shanghai, China: Preliminary results from a laboratory‐based surveillance, 2012‐2015

text: Acute respiratory infections (ARIs), with viral pathogens as the major contributors, are the most common illnesses worldwide, and increase the morbidity and mortality among the elderly population. The clinical and pathological features of elderly people with ARIs need to be identified for disease intervention. From January 1, 2012 through December 31, 2015, respiratory specimens from patients above 60 years old with ARIs were collected from the outpatient and inpatient settings of six sentinel hospitals in Pudong New Area. Each specimen was tested via multiplex polymerase chain reaction (PCR) for eight target viral etiologies including influenza, human rhinovirus (HRV), human para‐influenza virus (PIV), adenovirus (ADV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human coronavirus (hCoVs), and human bocavirus (hBoV). A total of 967 elderly patients with ARIs were enrolled, including 589 (60.91%) males, and the median age was 73 years old. 306 (31.64%) patients were tested positive for any one of the eight viruses, including 276 single infections and 30 co‐infections. Influenza was the predominant virus (14.17%, 137/967), detected from 21.35% (76/356) of the outpatients and 9.98% (61/611) of the inpatients. Influenza infections presented two annual seasonal peaks during winter and summer. Compared with non‐influenza patients, those with influenza were more likely to have fever, cough, sore throat, and fatigue. This study identified influenza as the leading viral pathogen among elderly with ARIs, and two seasonal epidemic peaks were observed in Shanghai. An influenza vaccination strategy needs to be advocated for the elderly population.


title: Implementation System of a Biosurveillance System in the Republic of Korea and Its Legal Ramifications

text: Laws are fundamental tools that regulate and manage various issues to protect the rights of the people in a society. Legislation on disease surveillance enables agencies to regulate and manage public health, including preventing the spread of infectious diseases. We assessed the Infectious Disease Prevention and Control Act of Korea (IDPCA) through the lens of biosurveillance to understand its effectiveness in protecting public health. In addition, the relevant legislation and regulations of the United States and the World Health Organization were examined. The evaluation concludes that the current IDPCA is limited in terms of providing guidance for early detection of and response to hazards using integrated data and an information-sharing system. Further revision of the laws is needed to enable early detection and warning of potential threats to public health.


title: Development of a nested PCR assay for the detection of canine coronavirus

text: Abstract A diagnostic test for canine coronavirus (CCV) infection based on a nested polymerase chain reaction (n-PCR) assay was developed and tested using the following coronavirus strains: CCV (USDA strain), CCV (45/93, field strain), feline infectious peritonitis virus (FIPV, field strain), trasmissible gastroenteritis virus (TGEV, Purdue strain), bovine coronavirus (BCV, 9WBL-77 strain), infectious bronchitis virus (IBV, M-41 strain) and fecal samples of dogs with CCV enteritis. A 230-bp segment of the gene encoding for transmembrane protein M of CCV is the target sequence of the primer. The test described in the present study was able to amplify both CCV and TGEV strains and also gave positive results on fecal samples from CCV infected dogs. n-PCR has a sensitivity as high as isolation on cell cultures, and can therefore be used for the diagnosis of CCV infection in dogs.


title: Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis.

text: Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.


title: Evolving sequence mutations in the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

text: BACKGROUND: Middle East respiratory syndrome coronavirus (MERS-CoV) has continued to cause sporadic outbreaks of severe respiratory tract infection over the last 8 years. METHODS: Complete genome sequencing using next-generation sequencing was performed for MERS-CoV isolates from cases that occurred in Riyadh between 2015 and 2019. Phylogenetic analysis and molecular mutational analysis were carried out to investigate disease severity. RESULTS: A total of eight MERS-CoV isolates were subjected to complete genome sequencing. Phylogenetic analysis resulted in the assembly of 7/8 sequences within lineage 3 and one sequence within lineage 4 showing complex genomic recombination. The isolates contained a variety of unique amino acid substitutions in ORF1ab (41), the N protein (10), the S protein (9) and ORF4b (5). CONCLUSION: Our study shows that MERS-CoV is evolving. The emergence of new variants carries the potential for increased virulence and could impose a challenge to the global health system. We recommend the sequencing every new MERS-CoV isolate to observe the changes in the virus and relate them to clinical outcomes.


COVID-19 - Comment vivre un confinement pour épidémie?


title: The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis

text: BACKGROUND: The effect of corticosteroids on clinical outcomes in patients with influenza pneumonia remains controversial. We aimed to further evaluate the influence of corticosteroids on mortality in adult patients with influenza pneumonia by comparing corticosteroid-treated and placebo-treated patients. METHODS: The PubMed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL), and Information Sciences Institute (ISI) Web of Science databases were searched for all controlled studies that compared the effects of corticosteroids and placebo in adult patients with influenza pneumonia. The primary outcome was mortality, and the secondary outcomes were mechanical ventilation (MV) days, length of stay in the intensive care unit (ICU LOS), and the rate of secondary infection. RESULTS: Ten trials involving 6548 patients were pooled in our final analysis. Significant heterogeneity was found in all outcome measures except for ICU LOS (I(2) = 38%, P = 0.21). Compared with placebo, corticosteroids were associated with higher mortality (risk ratio [RR] 1.75, 95% confidence interval [CI] 1.30 ~ 2.36, Z = 3.71, P = 0.0002), longer ICU LOS (mean difference [MD] 2.14, 95% CI 1.17 ~ 3.10, Z = 4.35, P < 0.0001), and a higher rate of secondary infection (RR 1.98, 95% CI 1.04 ~ 3.78, Z = 2.08, P = 0.04) but not MV days (MD 0.81, 95% CI − 1.23 ~ 2.84, Z = 0.78, P = 0.44) in patients with influenza pneumonia. CONCLUSIONS: In patients with influenza pneumonia, corticosteroid use is associated with higher mortality. TRIAL REGISTRATION: PROSPERO (ID: CRD42018112384). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13054-019-2395-8) contains supplementary material, which is available to authorized users.


title: Surveillance for Adenoviruses in Bats in Italy

text: Adenoviruses are important pathogens of humans and animals. Bats have been recognized as potential reservoirs of novel viruses, with some viruses being regarded as a possible zoonotic threat to humans. In this study, we report the detection and analysis of adenoviruses from different bat species in northern Italy. Upon sequence and phylogenetic analysis, based on a short diagnostic fragment of the highly-conserved DNA polymerase gene, we identified potential novel candidate adenovirus species, including an avian-like adenovirus strain. An adenovirus isolate was obtained in simian cell lines from the carcass of a Pipistrellus kuhlii, and the complete genome sequence was reconstructed using deep sequencing technologies. The virus displayed high nucleotide identity and virtually the same genome organization as the Pipistrellus pipistrellus strain PPV1, isolated in Germany in 2007. Gathering data on epidemiology and the genetic diversity of bat adenoviruses may be helpful to better understand their evolution in the mammalian and avian hosts.


title: Vaccine for the Economy

text: Given the global pandemic and the imminent economic crisis, it is important to understand what is happening in our economy and what the consequences will be. The world is looking for a vaccine for the pandemic; however COVID‐19 has affected not only the health of people but the health of the economy, and both need to be cured. What will be the vaccine for our economy? The Federal Reserve is introducing what they consider to be stabilizing measures. However, those measures can have negative effects on our economy and the financial system in the future, and it is crucial for us to understand how and why.


title: The relationship between fever rate and telework implementation as a social distancing measure against the COVID-19 pandemic in Japan

text: Abstract Objectives On March 28, the Japanese government decided on the "Basic Policies for Novel Coronavirus Disease (COVID-19) Control", and called on the public to thoroughly implement social distance measures (i.e. behavioral restrictions to limit the frequency and intensity of human contact), especially telework. Methods We used population-level questionnaire data from a social networking service (SNS) with 275,560 respondents from March 5 to April 6 to evaluate the relationship between telework implementation and the presence of a fever (body temperature above 37.5°C) within one month as a surrogate indicator of COVID-19 infection, by occupation type and age group. Results Among company employees, a statistical significance was identified in the 15–29 and 30–59 age groups, showing higher fever rates in the non-teleworker group (for 15–29 age group, non-teleworkers: 7.64%; teleworkers: 6.45%; p=0.02; for 30–59 age group, non-teleworkers: 3.46%; teleworkers: 3.14%; p=0.02). Conclusions Telework remains a controversial topic in Japan as the government called for emergency measures. While caution is warranted in interpreting our findings because our data is limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.


title: Polymeric architectures of bismuth citrate based on dimeric building blocks

text: Four bismuth complexes, (H(2)En)[Bi(2)(cit)(2)(H(2)O)(4/3)]·(H(2)O)(x) (1), (H(2)En)(3)[Bi(2)(cit)(2)Cl(4)]·(H(2)O)(x) (2), (HPy)(2)[Bi(2)(cit)(2)(H(2)O)(8/5)]·(H(2)O)(x) (3) and (H(2)En)[Bi(2)(cit)(2)](H(2)O)(x) (4) [cit = citrate(4−); En = ethylenediamine; Py = pyridine] have been synthesized and crystallized. The crystal structures reveal that the basic building blocks in all of these complexes are bismuth citrate dimeric units which combine to form polymeric architectures. The embedded protonated ethylenediamine and pyridine moieties in the polymeric frameworks have been identified by X-ray crystallography and solid-state cross polarization/magic angle spinning (CP/MAS) (13)C NMR. Based on the framework of complex 1, a structural model of a clinically used antiulcer drug, ranitidine bismuth citrate (RBC) was generated. The behavior of the protonated amine-bismuth citrate complexes in acidic aqueous solution has been studied by electrospray ionization-mass spectrometry (ESI-MS). ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11426-010-4113-x and is accessible for authorized users.


title: An ELISA based on recombinant spike protein S for the detection of antibodies to transmissible gastroenteritis virus of swine-like canine coronaviruses

text: Abstract Recombinant canine coronaviruses, resembling the transmissible gastroenteritis virus of swine (TGEV) in a 5′ fragment of the S glycoprotein, have been detected recently and showed to be present in canine populations. The 5′ fragment of the S protein (S′) of a TGEV-like canine coronavirus (CCoV), strain 174/06, was expressed in an Escherichia coli cell-free system. The purified recombinant polypeptide was employed to develop an ELISA test for the detection of TGEV-like CCoV-specific antibodies in dog sera. Four canine sera positive for TGEV-like CCoV, six sera positive to classical CCoV-II strains and 10 negative control sera were examined. The recombinant S′ was not recognized by antibodies to classical CCoV-II, as only sera from dogs infected experimentally with TGEV-like CCoV reacted strongly with the recombinant S′ polypeptide whereas dog sera with antibodies to classical CCoV-II did not react. As classical CCoV-II and TEGV-like CCoVs are related antigenically, the recombinant S′ ELISA is a useful method to investigate serologically the prevalence of TGEV-like CCoVs in dogs.


title: RNA Interference: From Basic Research to Therapeutic Applications

text: An efficient mechanism for the sequence‐specific inhibition of gene expression is RNA interference. In this process, double‐stranded RNA molecules induce cleavage of a selected target RNA (see picture). This technique has in recent years developed into a standard method of molecular biology. Successful applications in animal models have already led to the initiation of RNAi‐based clinical trials as a new therapeutic option.[Image: see text] Only ten years ago Andrew Fire and Craig Mello were able to show that double‐stranded RNA molecules could inhibit the expression of homologous genes in eukaryotes. This process, termed RNA interference, has developed into a standard method of molecular biology. This Review provides an overview of the molecular processes involved, with a particular focus on the posttranscriptional inhibition of gene expression in mammalian cells, the possible applications in research, and the results of the first clinical studies.


title: Care of patients with liver disease during the COVID-19 pandemic: EASL-ESCMID position paper

text: The coronavirus disease 2019 (COVID-19) pandemic poses an enormous challenge to healthcare systems in affected communities. Older patients and those with pre-existing medical conditions have been identified as populations at risk of a severe disease course. It remains unclear at this point to what extent chronic liver diseases should be considered as risk factors, due to a shortage of appropriate studies. However, patients with advanced liver disease and those after liver transplantation represent vulnerable patient cohorts with an increased risk of infection and/or a severe course of COVID-19. In addition, the current pandemic requires unusual allocation of healthcare resources which may negatively impact the care of patients with chronic liver disease that continue to require medical attention. Thus, the challenge hepatologists are facing is to promote telemedicine in the outpatient setting, prioritise outpatient contacts, avoid nosocomial dissemination of the virus to patients and healthcare providers, and at the same time maintain standard care for patients who require immediate medical attention.


title: Outbreak of Human Metapneumovirus in a Nursing Home: A Clinical Perspective

text: Abstract Objectives To describe a human metapneumovirus (hMPV) outbreak occurring in a nursing home for older adults and to identify the risk factors associated with the clinical infection. Design A retrospective, case-controlled study. Setting and participants A French nursing home for older adults between December 27, 2014 and January 20, 2015. Probable cases were residents presenting at least 1 respiratory symptom or 1 constitutional symptom. Confirmed cases identified in the same way as probable cases but with a positive RT-PCR test for hMPV. Controls were residents with no symptoms of respiratory infection. Measures Identification of hMPV was realized on nasal swab samples by RT-PCR. Results Seventy-eight older people were resident at the time of the outbreak. Three of the 4 tested were positive for hMPV by RT-PCR and negative for 13 other viruses or bacteria. All probable infected residents presented cough; other symptoms were scarcer. An inflammatory response was present, with median C-reactive protein at 50 mg/L. The median duration of the illness was 7 days. The rate of infection among residents was high (51%), with 5 hospitalizations (12.5%) and 1 death (2.5%). In multivariate analysis, vaccination against influenza virus appeared to emerge as associated with a probable hMPV infection, but this might be an artifact, as the proportion of unvaccinated residents was low (15%). A clear infected population profile was hard to define, although limited autonomy and low ADL score may play a role. Basic hygiene precautions were reinforced, but droplet precautions seemed difficult to apply rigorously to this population. Conclusions/Implications Clinical and biological presentations were nonspecific. The rate of infection was high, highlighting the need for the rapid introduction of strict precautions to contain the infection.


title: A self-assembled fusion protein-based surface plasmon resonance biosensor for rapid diagnosis of severe acute respiratory syndrome

text: Abstract A surface plasmon resonance (SPR)-based biosensor was developed for simple diagnosis of severe acute respiratory syndrome (SARS) using a protein created by genetically fusing gold binding polypeptides (GBPs) to a SARS coronaviral surface antigen (SCVme). The GBP domain of the fusion protein serves as an anchoring component onto the gold surface, exploiting the gold binding affinity of the domain, whereas the SCVme domain is a recognition element for anti-SCVme antibody, the target analyte in this study. SPR analysis indicated the fusion protein simply and strongly self-immobilized onto the gold surface, through GBP, without surface chemical modification, offering a stable and specific sensing platform for anti-SCVme detection. AFM and SPR imaging analyses demonstrated that anti-SCVme specifically bound to the fusion protein immobilized onto the gold-micropatterned chip, implying that appropriate orientation of bound fusion protein by GBP resulted in optimal exposure of the SCVme domain to the assay solution, resulting in efficient capture of anti-SCVme antibody. The best packing density of the fusion protein onto the SPR chip was achieved at the concentration of 10μgmL−1; this density showed the highest detection response (906RU) for anti-SCVme. The fusion protein-coated SPR chip at the best packing density had a lower limit of detection of 200ngmL−1 anti-SCVme within 10min and also allowed selective detection of anti-SCVme with significantly low responses for non-specific mouse IgG at all tested concentrations. The fusion protein provides a simple and effective method for construction of SPR sensing platforms permitting sensitive and selective detection of anti-SCVme antibody.


title: Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

text: Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here, we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB-dependent pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are not only linked to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history – in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.


title: Ultraviolet irradiation doses for coronavirus inactivation – review and analysis of coronavirus photoinactivation studies

text: Background: To slow the increasing global spread of the SARS-CoV-2 virus, appropriate disinfection techniques are required. Ultraviolet radiation (UV) has a well-known antiviral effect, but measurements on the radiation dose necessary to inactivate SARS-CoV-2 have not been published so far. Methods: Coronavirus inactivation experiments with ultraviolet light performed in the past were evaluated to determine the UV radiation dose required for a 90% virus reduction. This analysis is based on the fact that all coronaviruses have a similar structure and similar RNA strand length. Results: The available data reveals large variations, which are apparently not caused by the coronaviruses but by the experimental conditions selected. If these are excluded as far as possible, it appears that coronaviruses are very UV sensitive. The upper limit determined for the log-reduction dose (90% reduction) is approximately 10.6 mJ/cm(2) (median), while the true value is probably only 3.7 mJ/cm(2) (median). Conclusion: Since coronaviruses do not differ structurally to any great exent, the SARS-CoV-2 virus – as well as possible future mutations – will very likely be highly UV sensitive, so that common UV disinfection procedures will inactivate the new SARS-CoV-2 virus without any further modification.


title: Corticosteroid therapy in ENT in the context of the COVID-19 pandemic

text: ABSTRACT This consensus statement about the indications and modalities of corticosteroid treatment in the context of the COVID-19 pandemic was jointly written by experts from the French Association of Otology and Oto-Neurology (AFON) and from the French Society of Otorhinolaryngology, Head and Neck Surgery (SFORL). There is currently not enough data in favour of danger or benefit from corticosteroids in COVID-19, so until this matter is resolved it is advisable to limit their indications to the most serious clinical pictures for which it is well established that this type of treatment has a positive impact on the progression of symptoms. In Grade V and VI Bell's palsy according to the House-Brackmann grading system, a week’s course of oral corticosteroids is recommended. Corticosteroid therapy is also recommended in cases of sudden hearing loss of more than 60 dB, either in the form of intratympanic injections or a week’s course of oral medication. In rhinology, there is no indication for systemic corticosteroid therapy in the current situation. However, patients are advised to continue with their local corticosteroid therapy in the form of a nasal spray or by inhalation. Treatments with corticosteroid nasal sprays can still be prescribed if there is no alternative.


Genomics and computational science for virus research


title: Production of IFN-γ in feline whole blood after incubation with potential T-cell epitopes of the nucleocapsid protein of feline coronavirus

text: Abstract Interferon gamma (IFN-γ) plays an important role in cell mediated responses against mutated feline coronavirus strains (FCoV) involved in the pathogenesis of feline infectious peritonitis (FIP). The aim of this study was to establish a combined in silico and in vitro approach to assess feline leukocyte production of IFN-γ in response to selected peptides of the nucleocapside protein (N) of FCoVs. To this aim, we designed, through a bioinformatic approach, 8 potentially immunogenic peptides from the protein N corresponding to sequences of residues 14, 182, 198 detected only in FCoVs from FIP cats (virulent strains), only in FCoVs from healthy cats (avirulent strains) and both in FIP and in healthy cats (mixed strains). The peptides or a sham solution were incubated with whole blood from 16 cats (7 healthy and 9 with chronic diseases other than FIP) and IFN-γ concentration was measured on plasma using an ELISA system. RT-PCR expression of IFN-γ mRNA was also evaluated after incubation of the peptides or a sham solution with whole blood from 4 clinically healthy cats. The mean plasma concentration of IFN-γ in samples incubated with peptides decreased and the expression of IFN-γmRNA did not change compared with the sham solution, except for some cats with chronic diseases (which probably have a “pre-activated” immune response). These cats responded to “avirulent” or “mixed” peptides by increasing the concentration of IFN-γ and the expression of IFN-γ mRNA. The combined approach employed in this study allowed us to identify potentially immunogenic peptides of FCoV N protein that can modulate the production of IFN-γ especially in cats with a “pre-activated” cell mediated response.


title: Investigation of C-terminal domain of SARS nucleocapsid protein–Duplex DNA interaction using transistors and binding-site models

text: Abstract AlGaN/GaN high electron mobility transistors (HEMTs) were used to sense the binding between double stranded DNA (dsDNA) and the severe acute respiratory syndrome coronavirus (SARS-CoV) nucleocapsid protein (N protein). The sensing signals were the drain current change of the HEMTs induced by the protein–dsDNA binding. Binding-site models using surface coverage ratios were utilized to analyze the signals from the HEMT-based sensors to extract the dissociation constants and predict the number of binding sites. Two dissociation constants, K D1 =0.0955nM, K D2 =51.23nM, were obtained by fitting the experimental results into the two-binding-site model. The result shows that this technique is more competitive than isotope-labeling electrophoretic mobility shift assay (EMSA). We demonstrated that AlGaN/GaN HEMTs were highly potential in constructing a semiconductor-based-sensor binding assay to extract the dissociation constants of nucleotide–protein interaction.


title: The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report

text: Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5 days after initiation of remdesivir, was transitioned to room air 24 h later, and discharged at the completion of remdesivir therapy.


A pandemic is not a war: COVID‐19 urgent anthropological reflections


title: Targeted Delivery of siRNA

text: Therapeutic application of siRNA requires delivery to the correct intracellular location, to interact with the RNAi machinery within the target cell, within the target tissue responsible for the pathology. Each of these levels of targeting poses a significant barrier. To overcome these barriers several strategies have been developed, such as chemical modifications of siRNA, viral nucleic acid delivery systems, and nonviral nucleic acid delivery systems. Here, we discuss progress that has been made to improve targeted delivery of siRNA in vivo for each of these strategies.


title: Risk factors for contracting watery diarrhoea in Kadoma City, Zimbabwe, 2011: a case control study

text: BACKGROUND: Kadoma City experienced an increase in watery diarrhoea from 27 cases during week beginning 5(th) September, to 107 cases during week beginning 26(th) September 2011. The weekly diarrhoea cases crossed the threshold action line during week beginning 5(th) September at the children’s clinic in Rimuka Township, and the remaining four clinics reported cases crossing threshold action lines between week beginning 12(th) September and week beginning 26(th) September. Eighty-two percent of the cases were children less than 5 years old. We conducted a case controlstudy to determine risk factorsfor contracting watery diarrhoea in children less than 5 years in Kadoma City. METHODS: An unmatched 1:1 case control study was conducted in Ngezi and Rimuka townships in Kadoma City, Zimbabwe. A case was a child less than 5 years old, who developed acute watery diarrhoea between 5(th) September and 1(st) October 2011. A control was a child less than 5 years old who stayed in the same township and did not suffer from diarrhoea. A structured questionnaire was administered to caregivers of cases and controls.Laboratory water quality tests and stool test results were reviewed.Epi Info™ statistical software was used to analyse data. RESULTS: A total of 109 cases and 109 controls were enrolled. Independent protective factors were: having been exclusively breastfed for six months [AOR = 0.44; 95% CI (0.24-0.82)]; using municipal water [AOR = 0.38; 95% CI (0.18-0.80)]; using aqua tablets, [AOR = 0.49; 95% CI (0.26–0.94)] and; storing water in closed containers, [AOR = 0.24; 95% CI (0.07–0.0.83). The only independent risk factor for contracting watery diarrhoea was hand washing in a single bowl, [AOR = 2.89; 95% CI (1.33–6.28)]. Salmonella, Shigella, Rotavirus, and Enteropathogenic Escherichia coli were isolated in the stool specimens. None of the 33 municipal water samples tested showed contamination with Escherichia coli, whilst 23 of 44 (52%) shallow well water samples and 3 of 15(20%) borehole water samples tested were positive for Escherichia coli. CONCLUSIONS: The outbreak resulted from inadequate clean water and use of contaminated water. Evidence from this study was used to guide public health response to the outbreak.


title: Predicting Promiscuous T Cell Epitopes for Designing a Vaccine Against Streptococcus pyogenes

text: One of the most dangerous human pathogens with high prevalence worldwide is Streptococcus pyogenes, which has major impacts on global morbidity and mortality. A major challenge for S. pyogenes vaccine development is the detection of epitopes that confer protection from infection by multiple S. pyogenes types. Our aim was to identify the most conserved and immunogenic antigens of S. pyogenes, which can be a potential candidate for vaccine design in the future. Eight important surface proteins were analyzed. Using different prediction servers, strongest epitopes were selected. They had the ability to stimulate the humoral and cell-mediated immune system. Molecular docking was performed for measuring free-binding energy of selected epitopes. Seven epitopes from three surface proteins were selected as potential candidates for vaccine development. Conservation of selected epitopes among different Streptococcus types was checked. Further in vitro and in vivo tests are required to validate the suitability of the epitopes for vaccine design.


title: Innate Immune Signaling and Proteolytic Pathways in the Resolution or Exacerbation of SARS-CoV-2 in Covid-19: Key Therapeutic Targets?

text: COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive-polarity, single-stranded RNA genome. The initial outbreak of the pandemic began in December 2019, and it is affecting the human health of the global community. In common with previous pandemics (Influenza H1N1 and SARS-CoV) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus protein ligands (e.g., haemagglutinin or trimeric spike glycoprotein for Influenza and CoV, respectively) interact with cellular receptors, such as (depending on the virus) either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, e.g., cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family, such as Transmembrane protease serine 2 (TMPRSS2), are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) family members, which upregulate anti-viral and pro-inflammatory mediators [interleukin (IL)-6 and IL-8 and type I and type III Interferons among others], through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well-described “cytokine storm” and an ensuing multiple organ failure promoted by a downregulation of dendritic cell, macrophage, and T-cell function. We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through downregulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved with a view on tackling these therapeutically.


Implicación en Cataluña de los Servicios de Anestesiología y Reanimación en la pandemia por SARS-CoV2. Una solución real coste-efectiva para una crisis sanitaria sin precedentes


title: Synthesis and antiviral activities of hexadecyloxypropyl prodrugs of acyclic nucleoside phosphonates containing guanine or hypoxanthine and a (S)-HPMP or PEE acyclic moiety

text: Hexadecyloxypropyl esters of acyclic nucleoside phosphonates containing guanine (G) or hypoxanthine (Hx) and a (S)-[3-hydroxy-2-(phosphonomethoxy)propyl] [(S)-HPMP] or 2-(2-phosphonoethoxy)ethyl (PEE) acyclic moiety have been prepared. The activity of the prodrugs was evaluated in vitro against different virus families. Whereas ester derivatives of PEEHx and (S)-HPMPHx were antivirally inactive, monoesters of PEEG, and mono- and diesters of (S)-HPMPG showed pronounced antiviral activity against vaccinia virus and/or herpesviruses. Monoesters of (S)-HPMPG emerged as the most potent and selective derivatives against these DNA viruses. None of the compounds were inhibitory against RNA viruses and retroviruses.


title: Probabilistic risk assessment of the energy saving shortfall in energy performance contracting projects–A case study

text: Abstract Lack of a proper assessment method on performance risks in Energy Performance Contracting (EPC) projects is one of the reasons hindering the further development of energy service companies (ESCOs) market. This paper proposes a simulation-based method to evaluate the probability of energy saving shortfall taking into account the variations in the influential parameters, including weather conditions, occupancy, operating hours, thermostat set-point, etc., during the contract period. The proposed method involves the use of a detailed building energy simulation programme, sensitivity analysis and Monte Carlo simulation techniques. Empirical data is also used to develop the probability distribution functions for the identified parameters to simulate the actual yearly variations in the post-retrofit conditions. A real case study of replacement of heat rejection system for a central chiller plant in Hong Kong is used to demonstrate the application of this probabilistic method. The result shows that the possible energy savings after a 1-year retrofit period ranges from 393,000kWh (2.86%) to 1098,000kWh (10.8%) with 90% statistical significance.


title: Asymptomatic Middle East Respiratory Syndrome coronavirus infection using a serologic survey in Korea

text: OBJECTIVES: The rates of asymptomatic infection with Middle East Respiratory Syndrome (MERS) coronavirus vary. A serologic study was conducted to determine the asymptomatic MERS infection rate in healthcare workers and non-healthcare workers by exposure status. METHODS: Study participants were selected from contacts of MERS patients based on a priority system in 4 regions strongly affected by the 2015 MERS outbreak. A sero-epidemiological survey was performed in 1,610 contacts (average duration from exposure to test, 4.8 months), and the collected sera were tested using an enzyme-linked immunespecific assay (ELISA), immunofluorescence assay (IFA), and plaque reduction neutralization antibody test (PRNT). Among the 1,610 contacts, there were 7 ELISA-positive cases, of which 1 exhibited positive IFA and PRNT results. RESULTS: The asymptomatic infection rate was 0.060% (95% confidence interval, 0.002 to 0.346). The asymptomatic MERS case was a patient who had been hospitalized with patient zero on the same floor of the hospital at the same time. The case was quarantined at home for 2 weeks after discharge, and had underlying diseases, including hypertension, angina, and degenerative arthritis. CONCLUSIONS: The asymptomatic infection was acquired via healthcare-associated transmission. Thus, it is necessary to extend serologic studies to include inpatient contacts who have no symptoms.


title: CD209 (DC-SIGN) −336A>G promoter polymorphism and severe acute respiratory syndrome in Hong Kong Chinese

text: CD209 (DC-SIGN) is an important C-type lectin which acts a receptor of many pathogens. The single nucleotide polymorphism (SNP) −336A>G in the CD209 promoter has been demonstrated to regulate promoter activity and to be associated with several important infectious diseases, such as human immunodeficiency virus–1 (HIV-1), Mycobacterium tuberculosis, and Dengue fever. CD209 facilitates severe acute respiratory syndrome (SARS)–coronavirus spike protein-bearing pseudotype driven infection of permissive cells in vitro. In keeping with previously published findings, our in vitro studies confirmed that this SNP modulates gene promoter activity. Genetic association analysis of this SNP with clinico-pathologic outcomes in 824 serologic confirmed SARS patients showed that the −336AG/GG genotype SARS patients was associated with lower standardized lactate-dehydrogenase (LDH) levels compared with the −336AA patients (p = 0.014, odds ratio = 0.40). High LDH levels are known to be an independent predictor for poor clinical outcome, probably related to tissue destruction from immune hyperactivity. Hence, SARS patients with the CD209 −336 AA genotype carry a 60% chance of having a poorer prognosis. This association is in keeping with the role of CD209 in modulating immune response to viral infection. The relevance of these findings for other infectious diseases and inflammatory conditions would be worth investigating.


title: COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals

text: We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London’s regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.


title: Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine

text: A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.


title: Cryo-EM analysis of a feline coronavirus spike protein reveals a unique structure and camouflaging glycans

text: Feline infectious peritonitis virus (FIPV) is an alphacoronavirus that causes a nearly 100% mortality rate without effective treatment. Here we report a 3.3-Å cryoelectron microscopy (cryo-EM) structure of the serotype I FIPV spike (S) protein, which is responsible for host recognition and viral entry. Mass spectrometry provided site-specific compositions of densely distributed high-mannose and complex-type N-glycans that account for 1/4 of the total molecular mass; most of the N-glycans could be visualized by cryo-EM. Specifically, the N-glycans that wedge between 2 galectin-like domains within the S1 subunit of FIPV S protein result in a unique propeller-like conformation, underscoring the importance of glycosylation in maintaining protein structures. The cleavage site within the S2 subunit responsible for activation also showed distinct structural features and glycosylation. These structural insights provide a blueprint for a better molecular understanding of the pathogenesis of FIP.


title: Could India be the origin of next COVID-19 like epidemic?

text: Abstract The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.


title: In Vivo Antiviral Effects of U18666A Against Type I Feline Infectious Peritonitis Virus

text: Background: The cationic amphiphilic drug U18666A inhibits the proliferation of type I FIPV in vitro. In this study, we evaluated the in vivo antiviral effects of U18666A by administering it to SPF cats challenged with type I FIPV. Methods: Ten SPF cats were randomly assigned to two experimental groups. FIPV KU-2 were inoculated intraperitoneally to cats. The control group was administered PBS, and the U18666A-treated group was administered U18666A subcutaneously at 2.5 mg/kg on day 0, and 1.25 mg/kg on days 2 and 4 after viral inoculation. Results: Two of the five control cats administered PBS alone developed FIP. Four of the five cats administered U18666A developed no signs of FIP. One cat that temporarily developed fever, had no other clinical symptoms, and no gross lesion was noted on an autopsy after the end of the experiment. The FIPV gene was detected intermittently in feces and saliva regardless of the development of FIP or administration of U18666A. Conclusions: When U18666A was administered to cats experimentally infected with type I FIPV, the development of FIP might be suppressed compared with the control group. However, the number of animals with FIP is too low to establish anti-viral effect of U18666A in cats.


title: COVID-19: A promising cure for the global panic

text: Abstract The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.


title: Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function

text: Infections induce complex host responses linked to antiviral defense, inflammation, and tissue damage and repair. We hypothesized that the liver, as a central metabolic hub, may orchestrate systemic metabolic changes during infection. We infected mice with chronic lymphocytic choriomeningitis virus (LCMV), performed RNA sequencing and proteomics of liver tissue, and integrated these data with serum metabolomics at different infection phases. Widespread reprogramming of liver metabolism occurred early after infection, correlating with type I interferon (IFN-I) responses. Viral infection induced metabolic alterations of the liver that depended on the interferon alpha/beta receptor (IFNAR1). Hepatocyte-intrinsic IFNAR1 repressed the transcription of metabolic genes, including Otc and Ass1, which encode urea cycle enzymes. This led to decreased arginine and increased ornithine concentrations in the circulation, resulting in suppressed virus-specific CD8(+) T cell responses and ameliorated liver pathology. These findings establish IFN-I-induced modulation of hepatic metabolism and the urea cycle as an endogenous mechanism of immunoregulation. VIDEO ABSTRACT:


title: Reasoning of spike glycoproteins being more vulnerable to mutations among 158 coronavirus proteins from different species

text: In this study, we used the probabilistic models developed by us over the last several years to analyze 158 proteins from coronaviruses in order to determine which protein is more vulnerable to mutations. The results provide three lines of evidence suggesting that the spike glycoprotein is different from the other coronavirus proteins: (1) the spike glycoprotein is more sensitive to mutations, this is the current state of the spike glycoprotein, (2) the spike glycoprotein has undergone more mutations in the past, this is the history of spike glycoprotein, and (3) the spike glycoprotein has a bigger potential towards future mutations, this is the future of spike glycoprotein. Furthermore, this study gives a clue on the species susceptibility regarding different proteins. Figure Predictable and unpredictable portions in coronavirus proteins. The data are presented as median with interquartile range. * the predictable and unpredictable portions in spike glycoprotein group are statistically different from any other protein groups at p<0.05 level, except for hemagglutinin-esterase precursor group. # the predictable and unpredictable portions in spike glycoprotein group are statistically different from hemagglutinin-esterase precursor, membrane protein and nucleocapsid protein groups at p<0.05 level. † the predictable and unpredictable portions in spike glycoprotein group are statistically different from hemagglutinin-esterase precursor, and membrane protein groups at p<0.05 level. Electronic Supplementary Material is available for this article if you access the article at http://dx.doi.org/10.1007/s00894-004-0210-0.


title: Update on neurological manifestations of COVID-19

text: Novel coronavirus (severe acute respiratory syndrome coronavirus-2: SARS-CoV-2) has a high homology with other cousin of coronaviruses such as SARS and Middle East respiratory syndrome-related coronavirus (MERS). After outbreak of the SARS-CoV-2 in China, it has spread so fast around the world. The main complication of coronavirus disease 2019 (COVID-19) is respiratory failure, but several patients have also been admitted to the hospital with neurological symptoms. Direct invasion, hematogenic rout, retrograde and anterograde transport along peripheral nerves are considered as main neuroinvasion mechanisms of SARS-CoV-2. In the present study, we describe the possible routes for entering of SARS-CoV-2 into the nervous system. Then, the neurological manifestations of the SARS-CoV-2 infection in the central nervous system (CNS) and peripheral nervous system (PNS) are reviewed. Furthermore, the neuropathology of the virus and its impacts on other neurological disorders are discussed.


title: Rhinovirus 39 infection in allergic and nonallergic subjects

text: Abstract To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.


title: Evaluation of depression and anxiety levels and related factors among operating theatre workers during the novel Coronavirus (COVID-19) pandemic

text: Abstract Purpose Tremendous physical and psychological pressure has been placed on healthcare workers due to the outbreak of novel coronavirus disease 2019 (COVID-19). This study aimed to examine the anxiety and depression levels and related factors among healthcare professionals working in operating theatres (anesthetic technicians and nurses) during the COVID-19 pandemic. Design The universe of this descriptive study consisted of healthcare professionals working in operating theatres in various healthcare institutions in Turkey. Methods The data were collected online between 9 April 2020 and 12 April 2020 using a SurveyMonkey questionnaire (SurveyMonkey, San Mateo, California, United States) and healthcare workers who volunteered to participate in the study were contacted via the social media platforms Twitter, LinkedIn and WhatsApp and asked to answer the questionnaire. Statistical analysis was performed using the SPSS version 22.0 software. Findings In total, 702 healthcare professionals working in operating theatres participated in the study. The mean depression and anxiety scores of the participants were found to be 9.4±4.6 (min: 0–max: 21) and 10.0±4.5 (min: 0–max: 21), respectively. Depression scores were statistically significantly higher among females, single individuals, those who had children, those living with a person aged 60 years or older (p<0.05). Meanwhile, anxiety scores were statistically significantly higher among females, single individuals (including widowed and divorced), university graduates, those with at least one chronic disease and those whose workload increased (p<0.05). Conclusions The present study showed that anxiety and depression symptoms were high among healthcare professionals working in operating theatres. In order to reduce these symptoms, psychological conditions of healthcare professionals can be followed continuously and regularly via standard procedures, and necessary interventions can be provided in the early period.


title: Inhibition of the PI3K/AKT Signaling Pathway or Overexpression of Beclin1 Blocks Reinfection of Streptococcus pneumoniae After Infection of Influenza A Virus in Severe Community-Acquired Pneumonia

text: Streptococcus pneumoniae (S. pneumoniae) and viruses are considered as primary risks of community-acquired pneumonia (CAP), and the effects of co-infection bacterial and virus in the prognosis of patients with severe CAP (SCAP) are poorly described. Therefore, this study is conducted to investigate the regulation of Beclin1-PI3K/AKT axis in reinfection of S. pneumoniae after influenza A virus in mice model of bronchoalveolar lavage fluid (BALF). Samples of sputum and BALF were collected from patients with SCAP for etiological detection. The expression of each gene was determined by RT-qPCR and western blot analysis. Influenza A/PR/8/34 and S. pneumoniae were used to establish the mice model of reinfection pneumonia. The virus quantity, expression levels of inflammatory factors, bacterial load, and myeloperoxidase (MPO) activity were tested. HE staining was applied to observe histopathology of lung tissue. The expression of Beclin1 was downregulated and the PI3K/AKT pathway was activated in viral pneumonia. In vivo experiment, the reinfection of S. pneumoniae following influenza A virus infection increased the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice. In contrast, inhibition of the PI3K/AKT pathway or overexpression of Beclin1 reduced the number of S. pneumoniae population, the activity of MPO, and the expression of TNF-α, IL-6, and IFN-γ in BALF of mice reinfected with S. pneumoniae after influenza A virus infection. Collectively, our study demonstrates that inhibition of the PI3K/AKT signaling pathway or overexpressed Beclin1 alleviates reinfection of S. pneumoniae after influenza A virus infection in SCAP.


title: Covid‐19 pandemic: Infection control in dental health care of infected patients‐a state concept

text: In December 2019 an outbreak of a new corona virus was reported in the city Wuhan, China. End of January, the WHO declared this development as a public health emergency of international concern (WHO, 2020). Germany reported a rapidly increasing number of 186,461 infected persons in the period from February to June (Robert-Koch-Institut, 2020). This pandemic, caused by a respiratory disease, presents the dental profession with an unprecedented challenge in terms of dental care for the population.


title: Importance of coronavirus negative-strand genomic RNA synthesis prior to subgenomic RNA transcription

text: Abstract The (−)-strand viral RNAs that result from after infection of cells with coronaviruses, which possess RNA genomes of message polarity, are genomic-sized and subgenomic-sized. Each of the (−)-strand subgenomic RNAs corresponds in size to each of the subgenomic mRNA species that are made in infected cells. We tested whether (−)-strand subgenomic RNAs might initially be synthesized from the input single-stranded (+)-strand genomic RNA prior to the production of subgenomic mRNAs. We used a mouse hepatitis virus (MHV) defective interfering (DI) RNA, from which subgenomic RNA was produced in DI RNA-replicating cells, because this DI RNA had a functional MHV intergenic region inserted in its interior. MHV samples containing the DI particles were irradiated with UV-light and then superinfected into cells that had been infected with MHV 4 h prior to superinfection. Northern blot analysis of intracellular RNAs that were extracted 3 h after superinfection showed that genomic DI RNA and subgenomic DI RNA had similar UV-target sizes, indicating that (−)-strand genomic DI RNA synthesis from input genomic DI RNA probably occurred prior to the subgenomic-size DI RNA synthesis. We discuss why, in the course of coronavirus transcription, (−)-strand genomic-length coronavirus RNA synthesis might occur before subgenomic-sized RNAs of either polarity are made.


title: Bats and Academics: How Do Scientists Perceive Their Object of Study?

text: Bats are associated with conflicting perceptions among humans, ranging from affection to disgust. If these attitudes can be associated with various factors among the general public (e.g. social norms, lack of knowledge), it is also important to understand the attitude of scientists who study bats. Such reflexive information on the researchers community itself could indeed help designing adequate mixed communication tools aimed at protecting bats and their ecosystems, as well as humans living in their vicinity that could be exposed to their pathogens. Thus, we conducted an online survey targeting researchers who spend a part of their research activity studying bats. Our aim was to determine (1) how they perceive their object of study, (2) how they perceive the representation of bats in the media and by the general population, (3) how they protect themselves against pathogen infections during their research practices, and (4) their perceptions of the causes underlying the decline in bat populations worldwide. From the 587 completed responses (response rate of 28%) having a worldwide distribution, the heterogeneity of the scientists’ perception of their own object of study was highlighted. In the majority of cases, this depended on the type of research they conducted (i.e. laboratory versus field studies) as well as their research speciality. Our study revealed a high level of personal protection equipment being utilised against pathogens during scientific practices, although the role bats play as reservoirs for a number of emerging pathogens remains poorly known. Our results also disclosed the unanimity among specialists in attributing a direct role for humans in the global decline of bat populations, mainly via environmental change, deforestation, and agriculture intensification. Overall, the present study suggests the need for better communication regarding bats and their biology, their role within the scientific community, as well as in the general public population. As a consequence, increased knowledge regarding scientists’ perceptions of bats should improve the role scientists play in influencing the perception of bats by the general public.


title: Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis

text: Abstract Interferon inducible transmembrane protein (IFITM) family genes have been implicated in several cellular processes such as the homotypic cell adhesion functions of IFNs and cellular anti-proliferative activities. We previously showed that the IFITM3 single nucleotide polymorphisms (SNPs) associated with susceptibility to ulcerative colitis (UC). The present study aimed to investigate whether the polymorphisms in the IFITM1 gene are associated with susceptibility to UC. We also evaluated the expression levels in the putative functional promoter polymorphisms to determine the change of their activity. Gene expression profiles in the tissues obtained from human digestive tracts by RT-PCR, and the possible variation sites and SNPs of IFITM1 were identified by direct sequencing method. Genotype analysis in the IFITM1 SNPs was performed by high resolution melting and TaqMan probe analysis, and the haplotype frequencies of IFITM1 SNPs for multiple loci were estimated using the expectation maximization (EM) algorithm. The expression levels in the putative functional promoter polymorphisms were evaluated by performing a luciferase reporter assay. We identified two SNPs and two variation sites, g.-1920G>A (rs77537847), g.-1547delA (novel) and g.-416C>G (rs11246062) in the promoter region, and g.364delA (rs200576757) in intron 1. The genotype and allele frequencies of the g.-1920G>A polymorphism of IFITM1 gene in the UC patients were significantly different from those of the healthy controls (P =0.002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC.


title: Lopinavir/ritonavir did not shorten the duration of SARS CoV-2 shedding in patients with mild pneumonia in Taiwan

text: Abstract An increase of Ct values was 0.9 per day in 2 cases of COVID-19 treated with lopinavir/ritonavir (LPV/r), an increase was 1.0 per day in 3 cases without LPV/r through illness day 1–10, indicating that LPV/r did not shorten the duration of SARS CoV-2 shedding.


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title: Designed protein mimics of the Ebola virus glycoprotein GP2 α-helical bundle: Stability and pH effects

text: Ebola virus (EboV) belongs to the Filoviridae family of viruses that causes severe and fatal hemhorragic fever. Infection by EboV involves fusion between the virus and host cell membranes mediated by the envelope glycoprotein GP2 of the virus. Similar to the envelope glycoproteins of other viruses, the central feature of the GP2 ectodomain postfusion structure is a six-helix bundle formed by the protein's N- and C-heptad repeat regions (NHR and CHR, respectively). Folding of this six-helix bundle provides the energetic driving force for membrane fusion; in other viruses, designed agents that disrupt formation of the six-helix bundle act as potent fusion inhibitors. To interrogate determinants of EboV GP2-mediated membrane fusion, we designed model proteins that consist of the NHR and CHR segments linked by short protein linkers. Circular dichroism and gel filtration studies indicate that these proteins adopt stable α-helical folds consistent with design. Thermal denaturation indicated that the GP2 six-helix bundle is highly stable at pH 5.3 (melting temperature, T(m), of 86.8 ± 2.0°C and van't Hoff enthalpy, ΔH(vH), of −28.2 ± 1.0 kcal/mol) and comparable in stability to other viral membrane fusion six-helix bundles. We found that the stability of our designed α-helical bundle proteins was dependent on buffering conditions with increasing stability at lower pH. Small pH differences (5.3–6.1) had dramatic effects (ΔT(m) = 37°C) suggesting a mechanism for conformational control that is dependent on environmental pH. These results suggest a role for low pH in stabilizing six-helix bundle formation during the process of GP2-mediated viral membrane fusion.


title: COVID‐19 and hypertension—evidence and practical management: Guidance from the HOPE Asia Network

text: There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being. For the ongoing management of patients with hypertension, telemedicine‐based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID‐19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.


title: The determinants and consequences of adult nursing staff turnover: a systematic review of systematic reviews

text: BACKGROUND: Nurses leaving their jobs and the profession are an issue of international concern, with supply-demand gaps for nurses reported to be widening. There is a large body of existing literature, much of which is already in review form. In order to advance the usefulness of the literature for nurse and human resource managers, we undertook an overview (review of systematic reviews). The aim of the overview was to identify high quality evidence of the determinants and consequences of turnover in adult nursing. METHODS: Reviews were identified which were published between 1990 and January 2015 in English using electronic databases (the Cochrane Database of Systematic Reviews, MEDLINE, EMBASE, Applied Social Sciences Index and Abstracts, CINAHL plus and SCOPUS) and forward searching. All stages of the review were conducted in parallel by two reviewers. Reviews were quality appraised using the Assessment of Multiple Systematic Reviews and their findings narratively synthesised. RESULTS: Nine reviews were included. We found that the current evidence is incomplete and has a number of important limitations. However, a body of moderate quality review evidence does exist giving a picture of multiple determinants of turnover in adult nursing, with - at the individual level - nurse stress and dissatisfaction being important factors and -at the organisational level - managerial style and supervisory support factors holding most weight. The consequences of turnover are only described in economic terms, but are considered significant. CONCLUSIONS: In making a quality assessment of the review as well as considering the quality of the included primary studies and specificity in the outcomes they measure, the overview found that the evidence is not as definitive as previously presented from individual reviews. Further research is required, of rigorous research design, whether quantitative or qualitative, particularly against the outcome of actual turnover as opposed to intention to leave. TRIAL REGISTRATION: PROSPERO Registration 17 March 2015: CRD42015017613. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12913-017-2707-0) contains supplementary material, which is available to authorized users.


title: Diagnóstico de las faringitis estreptocócicas

text: La faringoamigdalitis es una infección muy frecuente en nuestro medio. Su etiología es múltiple, especialmente viral. El diagnóstico etiológico únicamente tiene interés en las faringoamigadalitis causadas por Streptococcus pyogenes o estreptococo betahemolítico del grupo A, puesto que se deben tratar con antibióticos para evitar las complicaciones, especialmente la fiebre reumática. El diagnóstico se ha basado clásicamente en el aislamiento de la bacteria a partir del exudado faríngeo. No hay un método estandarizado para la realización de estos cultivos en cuanto al medio de aislamiento, la atmósfera de incubación o las pruebas mínimas de identificación que se deben realizar. Actualmente, en el mercado se dispone de múltiples reactivos que, por diferentes técnicas inmunológicas, permiten la detección del antígeno directamente en la muestra clínica. La mayoría de éstas presenta buenos valores de sensibilidad y de especificidad, aportando la ventaja de un resultado rápido, especialmente si se realiza en la misma consulta médica. Hay diferentes protocolos o estrategias para la atención de los pacientes con faringoamigadalitis. En cualquier caso, cada centro debe valorar el rendimiento de la técnica de detección de antígeno que se decida implementar, puesto que los resultados varían en función de las indicaciones y el cuidado en la obtención de la muestra. Tonsillitis and pharyngitis are highly frequent infections in Spain with multiple causes, especially viruses. Etiologic diagnosis of pharyngitis is only important in Streptococcus pyogenes or group A β-hemolytic streptococcal infections because antibiotic therapy is mandatory to prevent further complications, especially acute rheumatic fever. Diagnosis has classically been based on bacterial isolation from throat swabs. There are no standardized methods for this culture in terms of culture medium, incubation atmosphere or the identification tests to be performed. Currently, a large number of commercial reagents are available, which, through different immunological techniques, allow direct antigen detection in the clinical sample. Most of these products show good sensitivity and specificity values, with the added advantage of providing a rapid result, especially if they are performed at points of care. Many guidelines for the management of patients with pharyngitis and tonsillitis are available. Nevertheless, as antigen detection results can vary in each center according to the indications and the care taken in sample extraction, the method chosen should be evaluated before implementation.


title: Practical application of CFD on environmentally sensitive architectural design at high density cities: A case study in Hong Kong

text: Abstract Concerns on negative effects of urbanization on the environment make the aerodynamic properties of urban areas increasingly important in architectural design, particularly at high density cities. Over the past few decades, a rapid development in Computational Fluid Dynamics (CFD) has resulted in the widespread use of this technique not only as an environmental research tool but also as an architectural design tool. However, given real building morphologies and particular architectural requirements for the modeling and data analysis, the frequently used methods in research work are unsuitable for practical application. Therefore, this study focuses on the practical application of CFD to bridge the gap between wind engineering and architectural design. This study aims to provide a framework to accurately predict the pedestrian level wind environment, and identify the wind-related design issues. The methods are provided to answer the questions encountered by wind consultants and architects, particularly those on the input boundary condition, simulation modeling, modeling verification, data collection and analysis. The hypothesis testing method is introduced in the framework to verify and evaluate the simulation results. A Hong Kong case study is presented to illustrate that the framework and methods can work well.


docid: wjdkrufo

title: Coinfección por SARS-CoV-2 y virus Epstein Barr


title: Biotic concerns in generating molecular diagnosis matrixes for 4 avian viruses with emphasis on Marek’s disease virus

text: Abstract The great advance in the field of diagnosis of avian viruses is reflecting the highly sophisticated molecular assays of the human and general virology in providing highly sensitive and fast methods of diagnosis. The present review will discuss the biotic factors and the complexities that became evident with the evolution of the novel molecular diagnostic assays with emphasis on 4 avian viruses, chicken anemia, infectious laryngotracheitis, turkey meningoencephalitis, but mainly on Marek’s disease virus. To create a biologically meaningful diagnosis, attention should be dedicated to various biotic factors and not only of the diagnostic assay. Included among the important factors are, (a) the sample examined and the sampling strategy, (b) the outcomes of the pathogen amplification ex vivo, (c) the sampling time and its reflection on the disease diagnosis, (d) the impact of simultaneous multiple virus-infections regarding the ability to demonstrate all pathogens and inter- and intra-interactions between the pathogens. A concerted consideration of the relevant factors and the use of advanced molecular diagnostic assay would yield biologically significant diagnosis in real-time that would beneficiate the poultry industry.


title: Acute lower respiratory infections on lung sequelae in Cambodia, a neglected disease in highly tuberculosis-endemic country

text: Summary Background Little is known about post-infectious pulmonary sequelae in countries like Cambodia where tuberculosis is hyper-endemic and childhood pulmonary infections are highly frequent. We describe the characteristics of hospitalized Cambodian patients presenting with community-acquired acute lower respiratory infections (ALRI) on post-infectious pulmonary sequelae (ALRIPS). Methods Between 2007 and 2010, inpatients ≥15 years with ALRI were prospectively recruited. Clinical, biological, radiological and microbiological data were collected. Chest radiographs were re-interpreted by experts to compare patients with ALRIPS, on previously healthy lungs (ALRIHL) and active pulmonary tuberculosis (TB). Patients without chest radiograph abnormality or with abnormality suggestive as other chronic respiratory diseases were excluded from this analysis. Results Among the 2351 inpatients with community-acquired ALRI, 1800 were eligible: 426 (18%) ALRIPS, 878 (37%) ALRIHL and 496 (21%) TB. ALRIPS patients had less frequent fever than other ALRI (p < 0.001) and more productive cough than ALRIHL (p < 0.001). Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas aeruginosa accounted for 83% of ALRIPS group positive cultures. H. influenzae and P. aeruginosa were significantly associated with ALRIPS compared with ALRIHL. Treatment was appropriate in 58% of ALRIPS patients. Finally, 79% of ALRIPS were not recognized by local clinicians. In-hospital mortality was low (1%) but probably underestimated in the ALRIPS group. Conclusion ALRIPS remains often misdiagnosed as TB with inappropriate treatment in low-income countries. Better-targeted training programs would help reduce the morbidity burden and financial costs.


title: The impact of imposed delay in elective pediatric neurosurgery: an informed hierarchy of need in the time of mass casualty crisis

text: SARS-CoV-2 COVID-19, coronavirus, has created unique challenges for the medical community after national guidelines called for the cancellation of all elective surgery. While there are clear cases of elective surgery (benign cranial cosmetic defect) and emergency surgery (hemorrhage, fracture, trauma, etc.), there is an unchartered middle ground in pediatric neurosurgery. Children, unlike adults, have dynamic anatomy and are still developing neural networks. Delaying seemingly elective surgery can affect a child’s already vulnerable health state by further impacting their neurocognitive development, neurologic functioning, and potential long-term health states. The purpose of this paper is to demonstrate that “elective” pediatric neurosurgery should be risk-stratified, and multi-institutional informed guidelines established.


Letter to the Editor regarding “COVID-19 and Neurosurgical Education in Africa”; How the pandemic is changing neurosurgical education in Morocco.


COVID-19 crisis exit phases


title: Guidance for the Procurement of COVID‐19 Convalescent Plasma: Differences between High and Low‐Middle Income Countries

text: BACKGROUND AND OBJECTIVES: COVID‐19 convalescent plasma (CCP) has been used, predominantly in high‐income countries (HICs) to treat COVID‐19; available data suggest the safety and efficacy of use. We sought to develop guidance for procurement and use of CCP, particularly in low and middle‐income countries (LMICs) for which data are lacking. MATERIALS AND METHODS: A multidisciplinary, geographically representative group of individuals with expertise spanning transfusion medicine, infectious diseases and hematology was tasked with the development of a guidance document for CCP, drawing on expert opinion, survey of group members and review of available evidence. Three subgroups (i.e. donor, product and patient) were established based on self‐identified expertise and interest. Here, the donor and product‐related challenges are summarized and contrasted between HICs and LMICs with a view to guide related practices. RESULTS: The challenges to advance CCP therapy are different between HICs and LMICs. Early challenges in HICs related to recruitment and qualification of sufficient donors to meet the growing demand. Antibody testing also posed a specific obstacle given lack of standardization, variable performance of the assays in use and uncertain interpretation of results. In LMICs, an extant transfusion deficit, suboptimal models of donor recruitment (e.g. reliance on replacement and paid donors), limited laboratory capacity for pre‐donation qualification and operational considerations could impede wide adoption. CONCLUSION: There has been wide scale adoption of CCP in many HICs, which could increase if clinical trials show efficacy of use. By contrast, LMICs, having received little attention, require locally applicable strategies for adoption of CCP.


title: Impact of global change on transmission of human infectious diseases

text: Global change, which refers to large-scale changes in the earth system and human society, has been changing the outbreak and transmission mode of many infectious diseases. Climate change affects infectious diseases directly and indirectly. Meteorological factors including temperature, precipitation, humidity and radiation influence infectious disease by modulating pathogen, host and transmission pathways. Meteorological disasters such as droughts and floods directly impact the outbreak and transmission of infectious diseases. Climate change indirectly impacts infectious diseases by altering the ecological system, including its underlying surface and vegetation distribution. In addition, anthropogenic activities are a driving force for climate change and an indirect forcing of infectious disease transmission. International travel and rural-urban migration are a root cause of infectious disease transmission. Rapid urbanization along with poor infrastructure and high disease risk in the rural-urban fringe has been changing the pattern of disease outbreaks and mortality. Land use changes, such as agricultural expansion and deforestation, have already changed the transmission of infectious disease. Accelerated air, road and rail transportation development may not only increase the transmission speed of outbreaks, but also enlarge the scope of transmission area. In addition, more frequent trade and other economic activities will also increase the potential risks of disease outbreaks and facilitate the spread of infectious diseases.


title: Protein glycosylation in infectious disease pathobiology and treatment

text: A host of bacteria and viruses are dependent on O-linked and N-linked glycosylation to perform vital biological functions. Pathogens often have integral proteins that participate in host-cell interactions such as receptor binding and fusion with host membrane. Fusion proteins from a broad range of disparate viruses, such as paramyxovirus, HIV, ebola, and the influenza viruses share a variety of common features that are augmented by glycosylation. Each of these viruses contain multiple glycosylation sites that must be processed and modified by the host post-translational machinery to be fusogenically active. In most viruses, glycosylation plays a role in biogenesis, stability, antigenicity and infectivity. In bacteria, glycosylation events play an important role in the formation of flagellin and pili and are vitally important to adherence, attachment, infectivity and immune evasion. With the importance of glycosylation to pathogen survival, it is clear that a better understanding of the processes is needed to understand the pathogen requirement for glycosylation and to capitalize on this requirement for the development of novel therapeutics.


title: Virome genomics: a tool for defining the human virome

text: High throughput, deep sequencing assays are powerful tools for gaining insights into virus–host interactions. Sequencing assays can discover novel viruses and describe the genomes of novel and known viruses. Genomic information can predict viral proteins that can be characterized, describe important genes in the host that control infections, and evaluate gene expression of viruses and hosts during infection. Sequencing can also describe variation and evolution of viruses during replication and transmission. This review recounts some of the major advances in the studies of virus–host interactions from the last two years, and discusses the uses of sequencing technologies relating to these studies.


Etiology of acute respiratory infections in infants: A prospective birth cohort study


title: Bactericidal assessment of nano-silver on emerging and re-emerging human pathogens

text: Abstract With the threat of the growing number of bacteria resistant to antibiotics, the re-emergence of previously deadly infections and the emergence of new infections, there is an urgent need for novel therapeutic agent. Silver in the nano form, which is being used increasingly as antibacterial agents, may extend its antibacterial application to emerging and re-emerging multidrug-resistant pathogens, the main cause of nosocomial diseases worldwide. In the present study, a completely bottom up method to prepare green nano-silver was used. To explore the action of nano-silver on emerging Bacillus megaterium MTCC 7192 and re-emerging Pseudomonas aeruginosa MTCC 741 pathogenic bacteria, the study includes an analysis of the bacterial membrane damage through Scanning Electron Microscope (SEM) as well as alternation of zeta potential and intracellular leakages. In this work, we observed genuine bactericidal property of nano-silver as compare to broad spectrum antibiotics against emerging and re-emerging mode. After being exposed to nano-silver, the membrane becomes scattered from their original ordered arrangement based on SEM observation. Moreover, our results also suggested that alternation of zeta potential enhanced membrane permeability, and beyond a critical point, it leads to cell death. The leakages of intracellular constituents were confirmed by Gas Chromatography-Mass Spectrometry (GC–MS). In conclusion, the combine results suggested that at a specific dose, nano-silver may destroy the structure of bacterial membrane and depress its activity, which causes bacteria to die eventually.


title: Inhibition of multiple strains of Venezuelan equine encephalitis virus by a pool of four short interfering RNAs

text: Abstract RNA interference, mediated by short interfering RNAs (siRNAs), has been shown to have activity against a wide range of viruses and is a promising new antiviral therapy. Using multiple siRNAs that target conserved areas of the genome allows for increased chances of antiviral activity against different viral strains and also helps to prevent the emergence of escape mutants. In this study, four siRNAs were designed to target areas of conserved sequence between divergent strains of Venezuelan equine encephalitis virus (VEEV). A pool of these siRNAs inhibited the replication of all six strains of VEEV tested. A single nucleotide mismatch at the extreme 3′ end of one of the siRNA sense strands did not affect antiviral activity but other mutations were not tolerated. Two strains of VEEV were tested for their abilities to overcome the inhibitory effects of RNA interference following 10 consecutive incubations in the presence of siRNAs. One strain remained susceptible throughout the course of the experiment but the other strain became resistant to the activity of siRNAs. Sequence analysis of the siRNA target sites in this strain showed that no mutations had been generated, indicating that the virus may had become resistant in some other manner. In the absence of effective antiviral drugs and vaccines to combat VEEV infection, these siRNAs offer a potential new therapeutic approach but, as with all antimicrobial agents, caution needs to be exercised with respect to the generation of resistance.


title: Application of Geospatial Technologies in the COVID-19 Fight of Ghana

text: The SARS-CoV-2 infections continue unabated in Ghana and globally. The identification of country dynamics of the virus, its spread, and country-specific interventions in tackling the menace including the application of geospatial technologies. This research sought to highlight the use of geospatial technologies in the fight against COVID-19 in Ghana with best practices from China where the infections originated from; present the trends in Ghana and model near future trends of the virus. It was evident that just as other places, Ghana has employed geospatial technologies and continues to ply unchartered paths in solutions. The trend in Ghana is in line with a population concentration and tends to record higher figures in the southern parts. It is modeled that through incessant mobility patterns, infections will spread through to the middle parts and then the northern parts. The research, therefore, recommends the use of infrared scanners to augment testing practices and enhanced tracing of infected persons as well as the use of drones for the distribution of essential services.


title: A replication-competent vesicular stomatitis virus for studies of SARS-CoV-2 spike-mediated cell entry and its inhibition

text: There is an urgent need for vaccines and therapeutics to prevent and treat COVID-19. Rapid SARS-CoV-2 countermeasure development is contingent on the availability of robust, scalable, and readily deployable surrogate viral assays to screen antiviral humoral responses, and define correlates of immune protection, and to down-select candidate antivirals. Here, we describe a highly infectious recombinant vesicular stomatitis virus bearing the SARS-CoV-2 spike glycoprotein S as its sole entry glycoprotein that closely resembles the authentic agent in its entry-related properties. We show that the neutralizing activities of a large panel of COVID-19 convalescent sera can be assessed in high-throughput fluorescent reporter assay with rVSV-SARS-CoV-2 S and that neutralization of the rVSV and authentic SARS-CoV-2 by spike-specific antibodies in these antisera is highly correlated. Our findings underscore the utility of rVSV-SARS-CoV-2 S for the development of spike-specific vaccines and therapeutics and for mechanistic studies of viral entry and its inhibition.


title: Follow-up and Management of Kidney Transplant Recipients During the COVID-19 Lockdown: the experience of an Italian Transplant Center, Including Two Cases of COVID-19 Pneumonia

text: Abstract Background COVID-19 is a new infectious disease which emerged in China in late 2019 and is now spreading around the world. Social distancing measures were needed to reduce transmission, and lockdown included restricted access to healthcare facilities. The impact of COVID-19 on transplant recipients is unknown but, considering their immunosuppression status and associated comorbidities, they should be considered a high risk population. Methods A kidney transplant center in Central Italy implemented a strategy to maintain follow-up of kidney transplant recipients by phone and e-mail during lockdown. Telephone interviews were used administer a clinical questionnaire to patients, and e-mail was used to receive the results of diagnostic tests conducted in outpatient settings. Results From March 17 to April 23, 2020, a total of 143 kidney transplant recipients were contacted. Twenty-eight patients needed in-hospital consultation for problems unrelated to COVID-19, 3 of whom needed hospitalization. Eleven patients were managed at home for mild urinary or respiratory diseases, and one was referred to the hematologist. We identified 2 suspected cases of COVID-19 infection, and referred them to hospital care. Immunosuppressive therapy was modulated, and intravenous corticosteroids and potentially effective antiviral therapy were administered, with a favorable outcome. Conclusion In the context of a lockdown, such as that occurring in response to COVID-19, we suggest implementing remote surveillance programs in kidney transplant recipients, with the help of any available technology, and offering medical consulting and logistic support as needed.