title: Equine arteritis virus-infected cells contain six polyadenylated virus-specific RNAs

text: Abstract The kinetics of equine arteritis virus growth and virus-specific RNA synthesis at 40° were determined in BHK-21 cells. Maximum titers of infectious virus (∼107 PFU/ml) were observed at 12 hr p.i., while incorporation of [3H]uridine into virus-specific RNA became detectable at 4 hr p.i. and increased to reach a maximum rate at 8 hr p.i. This RNA was labeled between 2.5 and 7 hr p.i. and isolated from infected cells. About 44% bound to oligo(dT)-cellulose; this material was denatured using glyoxal and dimethyl sulfoxide and analyzed by electrophoresis in a 1% agarose-urea gel. Six virus-specific RNA species were found having the following molecular weights: 4.3 × 106 (RNA1), 1.3 × 106 (RNA2), 0.9 × 106 (RNA3), 0.7 × 106 (RNA4), 0.3 × 106 (RNA5), and 0.2 × 106 (RNA6). RNA1 comigrated with the viral genome. Artifacts caused by defective interfering particles or breakdown of RNA were excluded. Subsequently, the target sizes of the templates for the synthesis of the genome-sized RNA and the five subgenomic RNAs were determined by uv transcription mapping. Infected cells were irradiated at 6.5 hr p.i. The effect o of reasing uv doses on the RNA synthesis was determined by quantitation of the individual RNAs after separation by agarose gel electrophoresis. The uv target sizes calculated for the templates for RNAs 2–5 were very close to the physical size of RNA1. The target size of the template of RNA6 was smaller (2.8 × 106 daltons), although much greater than its physical size. The data are consistent with a model in which the individual RNAs are derived from a larger precursor RNA molecule. The consequences of these findings for the taxonomy of Togaviridae are discussed.


title: Antimicrobial resistance is a global problem – a UK perspective

text: Increasingly we are reaching a situation where current antimicrobial medicines are no longer effective for common infections, and antimicrobial resistance (AMR) is becoming a global public health crisis. The reliance on antimicrobials such as antibiotics has become a major issue for both medicine and agriculture, particularly given the slow development of new medicines and pharmaceutical industry investment. The UK government has been working with other international bodies in the search for solutions to the many challenges AMR poses. Herbal medicines may provide a useful modality in the fight against AMR and can work solely or in tandem with current antimicrobial approaches. Recommendations for herbal medicine use during the COVID-19 outbreak have featured in Chinese national guidelines and policies, but UK strategies have no such guidance. More research is urgently needed to explore the biological plausibility and safety of herbal medicines to manage AMR. AMR is universal, affecting anyone and everyone, at any age and in any country. Investigating how such approaches can be integrated into western medicine will be important to elucidate.


title: Identification of critical active‐site residues in angiotensin‐converting enzyme‐2 (ACE2) by site‐directed mutagenesis

text: Angiotensin‐converting enzyme‐2 (ACE2) may play an important role in cardiorenal disease and it has also been implicated as a cellular receptor for the severe acute respiratory syndrome (SARS) virus. The ACE2 active‐site model and its crystal structure, which was solved recently, highlighted key differences between ACE2 and its counterpart angiotensin‐converting enzyme (ACE), which are responsible for their differing substrate and inhibitor sensitivities. In this study the role of ACE2 active‐site residues was explored by site‐directed mutagenesis. Arg273 was found to be critical for substrate binding such that its replacement causes enzyme activity to be abolished. Although both His505 and His345 are involved in catalysis, it is His345 and not His505 that acts as the hydrogen bond donor/acceptor in the formation of the tetrahedral peptide intermediate. The difference in chloride sensitivity between ACE2 and ACE was investigated, and the absence of a second chloride‐binding site (CL2) in ACE2 confirmed. Thus ACE2 has only one chloride‐binding site (CL1) whereas ACE has two sites. This is the first study to address the differences that exist between ACE2 and ACE at the molecular level. The results can be applied to future studies aimed at unravelling the role of ACE2, relative to ACE, in vivo.


title: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV): Kinetics of Infection in Lymphatic Organs and Lung

text: Pigs were infected by the oronasal route with European isolates of the porcine reproductive and respiratory syndrome virus (PRRSV; I10 and Cobbelsdorf). The kinetics of infection in lymphatic organs and the lung were analysed by immunofluorescence detection of virus antigen, re‐isolation of the virus and reverse transcription‐polymerase chain reaction (RT‐PCR) for PRRSV‐specific RNA. The kinetics of PRRSV infection proceeded in three phases, irrespective of the varying infestation of lymphatic organs within the first days post‐infection (p.i.). First, an early acute infection of lymphatic organs developed within the first week and was characterized by a high number of antigen‐positive macrophages. Second, a delayed acute infection of the lung was observed, which was most pronounced during the second and third week p.i. when a high number of infected alveolar macrophages was observed. The acute infection of lymphatic organs had resolved at this time. Infected cells in the lung were predominantly located in pneumonic lesions. Third, a persistent infection was demonstrated by RT‐PCR and immunohistology when the experiments were terminated at day 49 p.i. The virus persisted in lymphatic organs, especially in the tonsils, and in the lung. At this stage, indications for a re‐occurrence of acute infection were observed in restricted areas of the lung.


title: Study on release suppression of cinnamaldehyde from κ-carrageenan gel by HR-MASNMR and pulsed field gradient NMR (PFG-NMR)

text: Aiming toward the production and characterization of delicious and functional gel foods, this communication studies the flavor release from cinnamon-containing κ-carrageenan gel. Cinnamaldehyde, which provides the flavor of cinnamon, was released in a trace amount from the gel and detected by flame ionization detector gas chromatography. The retention of cinnamaldehyde in κ-carrageenan gel and the interaction between flavor and polysaccharide were investigated by high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) and pulsed-field gradient NMR (PFG NMR). The intact cinnamaldehyde in the gel was also observed by HR-MAS NMR. The relative mobility difference of the flavor and polysaccharide molecules was observed from the diffusion-ordered NMR spectrum of PFG NMR.


title: Immunization of Puppies in the Presence of Maternally Derived Antibodies Against Canine Distemper Virus

text: Summary Vaccination of dams with modified-live canine distemper virus (CDV) vaccines will elicit high concentrations of colostral antibody, that although vital for protection of the pup during the first weeks of life, can interfere with active vaccination against the virus. In the present study, 12 pups, 7–9 weeks of age, with maternally derived immunity to CDV, were vaccinated with a canarypox-vectored CDV vaccine. These pups were protected against intravenous challenge with CDV. Three littermate pups that were unvaccinated all developed clinical signs of infection after challenge, and two of these control pups died.


title: Epitope selection and their placement for increased virus neutralization in a novel vaccination strategy for porcine epidemic diarrhea virus utilizing the Hepatitis B virus core antigen

text: Abstract Porcine epidemic diarrhea virus (PEDV) is a member of the Alphacoronaviridae genus within the Coronaviridae family. It is the causative agent of porcine epidemic diarrhea, a disease that can have mortality rates as high as 100% in suckling piglets. PEDV causes severe economic loss, and has been in existence for decades. A panzootic starting in 2010 renewed interest in the development of a universal vaccine toward PEDV. This report details several design changes made to a Hepatitis B virus core antigen (HBcAg)-based recombinant vaccine strategy, and their effect in vivo. Initially, several multi-antigen vaccine candidates were able to elicit antibodies specific to three out of four B-cell epitopes inserted into the chimeric proteins. However, a lack of virus neutralization led to a redesign of the vaccines. The focus of the newly redesigned vaccines was to elicit a strong immune response to the YSNIGVCK amino acid motif from PEDV. Genetically modified new vaccine candidates were able to elicit a strong antibody (Ab) response to the YSNIGVCK epitope, which correlated with an increased ability to neutralize the CO strain of PEDV. Additionally, the location of the inserted PEDV epitopes within the vector protein was shown to affect the immune recognition toward the native HBcAg during vaccination.


title: Evaluation of the efficacy of a commercial inactivated genogroup 2b-based porcine epidemic diarrhea virus (PEDV) vaccine and experimental live genogroup 1b exposure against 2b challenge

text: Porcine epidemic diarrhea virus strains from the G1b cluster are considered less pathogenic compared to the G2b cluster. The aim of this study was to compare the ability of G1b-based live virus exposure against use of a commercial G2b–based inactivated vaccine to protect growing pigs against G2b challenge. Thirty-nine PEDV naïve pigs were randomly divided into five groups: EXP-IM-1b (intramuscular G1b exposure; G2b challenge), EXP-ORAL-1b (oral G1b exposure; G2b challenge), VAC-IM-2b (intramuscular commercial inactivated G2b vaccination; G2b challenge), POS-CONTROL (sham-vaccination; G2b challenge) and NEG-CONTROL (sham-vaccination; sham-challenge). Pigs were vaccinated/exposed at 3 weeks of age (day post-vaccination 0, dpv 0), VAC-IM-2b pigs were revaccinated at dpv 14, and the pigs were challenged at dpv 28. Among all groups, VAC-IM-2b pigs had significantly higher anti-PEDV IgG levels on dpv 21 and 28 while EXP-ORAL-1b pigs had significantly higher anti-PEDV IgA levels on dpv 14, 21, 28 and 35. EXP-ORAL-1b also had detectable IgA in feces. Intramuscular PEDV exposure did not result in a detectable antibody response in EXP-IM-1b pigs. The fecal PEDV RNA levels in VAC-IM-2b pigs were significantly lower 5–7 days after challenge compared to the POS-CONTROL group. Under the study conditions a commercial inactivated G2b-based vaccine protected pigs against G2b challenge, as evidenced by reduction of PEDV RNA in feces for 3–4 logs during peak shedding and a shorter viral shedding duration. The oral, but not the intramuscular, experimental G1b-based live virus exposure induced a high anti-PEDV IgA response prior to challenge, which apparently did not impact PEDV shedding compared to POS-CONTROL pigs.


title: Coupled disease–behavior dynamics on complex networks: A review

text: Abstract It is increasingly recognized that a key component of successful infection control efforts is understanding the complex, two-way interaction between disease dynamics and human behavioral and social dynamics. Human behavior such as contact precautions and social distancing clearly influence disease prevalence, but disease prevalence can in turn alter human behavior, forming a coupled, nonlinear system. Moreover, in many cases, the spatial structure of the population cannot be ignored, such that social and behavioral processes and/or transmission of infection must be represented with complex networks. Research on studying coupled disease–behavior dynamics in complex networks in particular is growing rapidly, and frequently makes use of analysis methods and concepts from statistical physics. Here, we review some of the growing literature in this area. We contrast network-based approaches to homogeneous-mixing approaches, point out how their predictions differ, and describe the rich and often surprising behavior of disease–behavior dynamics on complex networks, and compare them to processes in statistical physics. We discuss how these models can capture the dynamics that characterize many real-world scenarios, thereby suggesting ways that policy makers can better design effective prevention strategies. We also describe the growing sources of digital data that are facilitating research in this area. Finally, we suggest pitfalls which might be faced by researchers in the field, and we suggest several ways in which the field could move forward in the coming years.


First impressions of performing bedside cognitive assessment of COVID‐19 inpatients.


title: The status of training in new technologies in advanced endoscopy: from defining competence to credentialing and privileging

text: Abstract The landscape of advanced endoscopy continues to evolve as new technologies and techniques become available. Although postgraduate advanced endoscopy fellowships have traditionally centered on ERCP and diagnostic EUS, the breadth of training has increased over the years in response to the ever-growing demand for therapeutic endoscopy. The increasing diversity and complexity of emerging endoscopic techniques accompanied by the shift in focus toward competency-based medical education requires innovative changes to the curriculum that will ensure adequate training yet without compromising best patient practices. The purpose of this review is to highlight the expansive array of advanced endoscopic procedures and the challenges of both defining and measuring competence during training. All authors are interventional endoscopists at their respective institutions performing these complex procedures, as well as training fellows in these techniques. We share our perspectives based on our experience navigating through these issues at our institutions and discuss strategies to standardize training and how to potentially incorporate these measures toward the process of credentialing and privileging in endoscopy.


title: Monoclonal antibody-based therapies for microbial diseases

text: The monoclonal antibody (mAb) revolution that currently provides many new options for the treatment of neoplastic and inflammatory diseases has largely bypassed the field of infectious diseases. Only one mAb is licensed for use against an infectious disease, although there are many in various stages of development. This situation is peculiar given that serum therapy was one of the first effective treatments for microbial diseases and that specific antibodies have numerous antimicrobial properties. The underdevelopment and underutilization of mAb therapies for microbial diseases has various complex explanations that include the current availability of antimicrobial drugs, small markets, high costs and microbial antigenic variation. However, there are signs that the climate for mAb therapeutics in infectious diseases is changing given increasing antibiotic drug resistance, the emergence of new pathogenic microbes for which no therapy is available, and development of mAb cocktail formulations. Currently, the major hurdle for the widespread introduction of mAb therapies for microbial diseases is economic, given the high costs of immunoglobulin preparations and relatively small markets. Despite these obstacles there are numerous opportunities for mAb development against microbial diseases and the development of radioimmunotherapy provides new options for enhancing the magic bullet. Hence, there is cautious optimism that the years ahead will see more mAbs in clinical use against microbial diseases.


title: CEACAM1: Expression and Role in Melanocyte Transformation

text: Metastases represent the main cause of death in melanoma patients. Despite the current optimized targeted therapy or immune checkpoint inhibitors the treatment of metastatic melanoma is unsatisfactory. Because of the poor prognosis of advanced melanoma there is an urgent need to identify new biomarkers to differentiate melanoma cells from normal melanocytes, to stratify patients according to their risk, and to identify subgroups of patients that require close follow-up or more aggressive therapy. Furthermore, melanoma progression has been associated with the dysregulation of cell adhesion molecules. We have reviewed the literature and have discussed the important role of the expression of the carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) in the development of melanoma. Thus, novel insights into CEACAM1 may lead to promising strategies in melanoma treatment, in monitoring melanoma patients, in assessing the response to immunotherapy, and in completing the standard immunohistochemical panel used in melanoma examination.


title: A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L

text: The OAS/RNase L pathway is one of the best-characterized effector pathways of the IFN antiviral response. It inhibits the replication of many viruses and ultimately promotes apoptosis of infected cells, contributing to the control of virus spread. However, viruses have evolved a range of escape strategies that act against different steps in the pathway. Here we unraveled a novel escape strategy involving Theiler’s murine encephalomyelitis virus (TMEV) L* protein. Previously we found that L* was the first viral protein binding directly RNase L. Our current data show that L* binds the ankyrin repeats R1 and R2 of RNase L and inhibits 2’-5’ oligoadenylates (2-5A) binding to RNase L. Thereby, L* prevents dimerization and oligomerization of RNase L in response to 2-5A. Using chimeric mouse hepatitis virus (MHV) expressing TMEV L*, we showed that L* efficiently inhibits RNase L in vivo. Interestingly, those data show that L* can functionally substitute for the MHV-encoded phosphodiesterase ns2, which acts upstream of L* in the OAS/RNase L pathway, by degrading 2-5A.


title: The practice of infection control and applied epidemiology: A historical perspective

text: The United States health care system and patient populations have changed substantially over the past several decades. The practice of infection control also has evolved since the landmark Study on the Efficacy of Nosocomial Infection Control project, and infection control professionals (ICPs) must continue to develop the knowledge and skills necessary to practice infection prevention and control. Practice analyses of infection control conducted between 1982 and 2001 were analyzed to determine changes in practice. These data reflect a 145% increase in infection control activities over a 20-year period. However, resources for infection control and prevention have not kept pace with this increased activity. In addition, the current trend toward mandatory reporting of health care-associated infections (HAIs) among several states will add more tasks for ICPs with limited resources, at the risk of spending less time on prevention and control activities. In keeping with its philosophy of quality health care and responsible public reporting, the Association of Professionals in Infection Control and Epidemiology, Inc, continues to explore the issue of mandatory reporting of HAIs.


title: Differential response of porcine immature monocyte-derived dendritic cells to virulent and inactivated transmissible gastroenteritis virus

text: Abstract Exposure of piglets less than 2 weeks of age to virulent transmissible gastroenteritis virus (TGEV) gives rise to mortality as high as 100%, and adult pigs recovering from its infection often become TGEV carriers. These facts suggest an evasion of the immune system by virulent TGEV. In this study, we showed that a virulent TGEV SHXB strain could infect porcine immature monocyte-derived dendritic cells (Mo-DCs), and down-regulate cell surface markers (SLA-II-DR, CD1a and CD80/86). Moreover, SHXB-infected immature Mo-DCs showed low expression of IL-12 and IFN-γ, and also lost the ability to stimulate T cell proliferation. Finally, SHXB inhibited the activation of nuclear factor kappa B (NF-κB) in these cells. Instead, UV-inactivated SHXB (UV-SHXB) had the opposite effects in immature Mo-DCs. In conclusion, the virulent SHXB could severely impair immature Mo-DCs, which might be involved in the pathogenesis of virulent TGEV in vivo.


title: Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome—Associated Coronavirus and Human Coronaviruses 229E and OC43

text: Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ⩾4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E.


COVID-19 and Racial Disparities


Abstracts der 54. Jahrestagung der Österreichischen Gesellschaft für Kinder- und Jugendheilkunde


title: A Computational Approach for Predicting Role of Human MicroRNAs in MERS-CoV Genome

text: The new epidemic Middle East Respiratory Syndrome (MERS) is caused by a type of human coronavirus called MERS-CoV which has global fatality rate of about 30%. We are investigating potential antiviral therapeutics against MERS-CoV by using host microRNAs (miRNAs) which may downregulate viral gene expression to quell viral replication. We computationally predicted potential 13 cellular miRNAs from 11 potential hairpin sequences of MERS-CoV genome. Our study provided an interesting hypothesis that those miRNAs, that is, hsa-miR-628-5p, hsa-miR-6804-3p, hsa-miR-4289, hsa-miR-208a-3p, hsa-miR-510-3p, hsa-miR-18a-3p, hsa-miR-329-3p, hsa-miR-548ax, hsa-miR-3934-5p, hsa-miR-4474-5p, hsa-miR-7974, hsa-miR-6865-5p, and hsa-miR-342-3p, would be antiviral therapeutics against MERS-CoV infection.


title: Postponed ICOM 2020 is now taking place in December

text: The 12th International Congress on Membranes & Membrane Processes (ICOM 2020) is now scheduled to be held on 6–11 December 2020 instead of 12–17 July 2020. It is still set to be held at the Excel Convention Centre in London, UK.


COVID-19 is Out of Proportion in African Americans. This Will Come as No Surprise…


title: Hepatocyte growth factor suppresses acute renal inflammation by inhibition of endothelial E-selectin

text: Vascular endothelial activation, marked by de novo expression of E-selectin, is an early and essential event in the process of leukocyte extravasation and inflammation. Evidence suggests that hepatocyte growth factor (HGF) ameliorates inflammation in animal models of renal disease, implying that HGF might inhibit specific components of the inflammatory response. This study examined the effect of HGF on endothelial E-selectin expression in acute inflammation induced by tumor necrosis factor (TNF)-α. In vitro, HGF suppressed TNF-α-induced cell surface expression of E-selectin in human umbilical vein endothelial cells (HUVEC) and inhibited E-selectin mediated monocytic adhesion to endothelial monolayers. HGF activated phosphatidylinositol 3-kinase (PI3K)–Akt that in turn inhibited its downstream transducer glycogen synthase kinase (GSK)3. Blockade of the PI3K–Akt pathway with specific inhibitors abrogated HGF induced inhibitory phosphorylation of GSK3 and suppression of E-selectin. In addition, selective inhibition of GSK3 activity by lithium suppressed TNF-α-induced E-selectin expression and monocytic adhesion, reminiscent of the action of HGF. Moreover, ectopic expression of an uninhibitable mutant GSK3β, in which the regulatory serine-9 is replaced by alanine, abolished HGF's suppressive effect on endothelial E-selectin. In vivo, administration of exogenous HGF reduced endothelial expression of E-selectin induced by bolus injection of TNF-α. This was associated with less sequestration of circulating fluorescence-labeled macrophages in the kidney. These findings suggest that HGF ameliorates acute renal inflammation in part by downregulating E-selectin mediated macrophage adhesion to the inflamed endothelium.


title: SARS-Coronavirus ancestor’s foot-prints in South-East Asian bat colonies and the refuge theory

text: Abstract One of the great challenges in the ecology of infectious diseases is to understand what drives the emergence of new pathogens including the relationship between viruses and their hosts. In the case of the emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), several studies have shown coronavirus diversity in bats as well as the existence of SARS-CoV infection in apparently healthy bats, suggesting that bats may be a crucial host in the genesis of this disease. To elucidate the biogeographic origin of SARS-CoV and investigate the role that bats played in its emergence, we amplified coronavirus sequences from bat species captured throughout Thailand and assessed the phylogenetic relationships to each other and to other published coronavirus sequences. To this end, RdRp sequence of Coronavirinae was targeted by RT-PCR in non-invasive samples from bats collected in Thailand. Two new coronaviruses were detected in two bat species: one Betacoronavirus in Hipposideros larvatus and one Alphacoronavirus in Hipposideros armiger. Interestingly, these viruses from South-East Asia are related to those previously detected in Africa (Betacoronavirus-b) or in Europe (Alphacoronavirus & Betacoronavirus-b). These findings illuminate the origin and the evolutionary history of the SARS-CoV group found in bats by pushing forward the hypothesis of a Betacoronavirus spill-over from Hipposideridae to Rhinolophidae and then from Rhinolophidae to civets and Human. All reported Betacoronaviruses-b (SARS-CoV group) of Hipposideridae and Rhinolophidae respectively cluster in two groups despite their broad geographic distribution and the sympatry of their hosts, which is in favor of an ancient and genetically independent evolution of Betacoronavirus-b clusters in these families. Moreover, despite its probable pathogenicity, we found that a Betacoronavirus-b can persistently infect a medium-sized hipposiderid bat colony. These findings illustrate the importance of the host phylogeny and the host/pathogen ecological interactions in the description and the understanding of pathogen emergence. The host’s phylogeny, biogeography and behaviour, combined with already described roles of pathogen plasticity and anthropic changes are likely to be co-factors of disease emergence. Elucidating the common ancestor of Hipposideridae and Rhinolophidae is key to understanding the evolutionary history of actual betacoronaviruses and therefore to get an insight of the deep origin of SARS-CoV.


title: Climate Change and Health: Transcending Silos to Find Solutions

text: Abstract Background Climate change has myriad implications for the health of humans, our ecosystems, and the ecological processes that sustain them. Projections of rising greenhouse gas emissions suggest increasing direct and indirect burden of infectious and noninfectious disease, effects on food and water security, and other societal disruptions. As the effects of climate change cannot be isolated from social and ecological determinants of disease that will mitigate or exacerbate forecasted health outcomes, multidisciplinary collaboration is critically needed. Objectives The aim of this article was to review the links between climate change and its upstream drivers (ie, processes leading to greenhouse gas emissions) and health outcomes, and identify existing opportunities to leverage more integrated global health and climate actions to prevent, prepare for, and respond to anthropogenic pressures. Methods We conducted a literature review of current and projected health outcomes associated with climate change, drawing on findings and our collective expertise to review opportunities for adaptation and mitigation across disciplines. Findings Health outcomes related to climate change affect a wide range of stakeholders, providing ready collaborative opportunities for interventions, which can be differentiated by addressing the upstream drivers leading to climate change or the downstream effects of climate change itself. Conclusions Although health professionals are challenged with risks from climate change and its drivers, the adverse health outcomes cannot be resolved by the public health community alone. A phase change in global health is needed to move from a passive responder in partnership with other societal sectors to drive innovative alternatives. It is essential for global health to step outside of its traditional boundaries to engage with other stakeholders to develop policy and practical solutions to mitigate disease burden of climate change and its drivers; this will also yield compound benefits that help address other health, environmental, and societal challenges.


title: COVID‐19 in Spain: Transplantation in the midst of the pandemic

text: Spain has been one of the most affected countries by the COVID‐19 outbreak. As of April 28, 2020, the number of confirmed cases is 210 773, including 102 548 patients recovered, more than 10 300 admitted to the ICU, and 23 822 deaths, with a global case fatality rate of 11.3%. From the perspective of donation and transplantation, the Spanish system first focused on safety issues, providing recommendations for donor evaluation and testing, and to rule out SARS‐CoV‐2 infection in potential recipients prior to transplantation. Since the country entered into an epidemiological scenario of sustained community transmission and saturation of intensive care, developing donation and transplantation procedures has become highly complex. Since the national state of alarm was declared in Spain on March 13, 2020, the mean number of donors has declined from 7.2 to 1.2 per day, and the mean number of transplants from 16.1 to 2.1 per day. Increased mortality on the waiting list may become a collateral damage of this terrible pandemic.


title: Evaluation of fast-track diagnostics and TaqMan array card real-time PCR assays for the detection of respiratory pathogens

text: Abstract Several commercial assays are now available to detect the nucleic acid of multiple respiratory pathogens from a single specimen. Head-to-head comparisons of such assays using a single set of standard specimens provide additional information about key assay parameters such as sensitivity, specificity and lower limits of detection, and help to inform the decision regarding which method to use. We evaluated two real-time PCR platforms: the Fast-track Diagnostics® (FTD) multiplex respiratory panel and a TaqMan array card (TAC) for simultaneous uniplex detection of multiple respiratory pathogens. Two sets of samples were used to evaluate the assays. One set was created by spiking pooled nasal wash or phosphate buffered saline with specified volumes of known concentrations of virus and/or bacteria. Clinical nasal wash specimens from children with lower respiratory tract illness comprised the other set. Thirteen pathogen targets were compared between the two platforms. Testing with a validation panel of spiked samples revealed a sensitivity of 96.1% and 92.9% for the FTD and TAC assays, respectively. Specificity could not be reliably calculated due to a suspected contamination of the sample substrate. Inter-assay agreement was high (>95%) for most targets. Previously untested clinical specimens tested by both assays revealed a high percent agreement (>95%) for all except rhinovirus, enterovirus and Streptococcus pneumoniae. Limitations of this evaluation included extraction of the validation samples by two different methods and the evaluation of the assays in different laboratories. However, neither of these factors significantly impacted inter-assay agreement for these sets of samples, and it was demonstrated that both assays could reliably detect clinically relevant concentrations of bacterial and viral pathogens.


title: Community-acquired pneumonia in children: cell-free plasma sequencing for diagnosis and management

text: Abstract Community-acquired pneumonia (CAP) is a common cause of pediatric hospital admission. Empiric antibiotic therapy for hospitalized children with serious CAP now targets the most likely pathogen(s), including those that may demonstrate significant antibiotic resistance. Cell-free plasma next-generation sequencing (CFPNGS) was first made available for Pediatric Infectious Diseases physicians in June 1, 2017, to supplement standard-of-care diagnostic techniques. A retrospective chart review was performed for children hospitalized with CAP between June 1, 2017, and January 22, 2018, to evaluate the impact of CFPNGS. We identified 15 hospitalized children with CAP without other underlying medical conditions for whom CFPNGS was performed. CFPNGS identified a pathogen in 13 of 15 (86%) children compared with 47% for those using standard culture and PCR-based methods alone. Changes in antibiotic management were made in 7 of 15 (47%) of children as a result of CFPNGS.


title: SARS‐CoV‐2: At the Crossroad Between Aging and Neurodegeneration

text: The recent global severe acute respiratory distress syndrome coronavirus 2 pandemic is changing the world we live in. As we learn about the virus and the pandemic, it is becoming evident that it is an age-associated problem that affects the human population. Severe acute respiratory distress syndrome coronavirus 2 is one of seven coronaviruses known to infect humans. These are large enveloped non-segmented positive-sense RNA viruses. Our knowledge of severe acute respiratory distress syndrome coronavirus 2 is extremely recent but is growing daily. There are currently no antiviral treatments against the virus or vaccines for its prevention. The long term consequences of the infection on human health remain uncertain but extrapolations can be made about the potential effects of the virus on cellular lifespan as well as on organismal healthspan. Here, we posit that severe acute respiratory distress syndrome coronavirus 2 infection may, in the long-term, lead to accelerated aging phenotypes in survivors, not only in affected tissues but also in other organs, including the brain. Since some of the effects could manifest months or years after infection, it will be necessary to follow carefully people affected by coronavirus disease 2019. Keeping accurate registries may enable us to, in the future, establish connections with aging-associated disorders, such as Parkinson's disease and other neurodegenerative disorders. This article is protected by copyright. All rights reserved.


title: Addressing the triple burden of malnutrition in the time of COVID-19 and climate change in Small Island Developing States: what role for improved local food production?

text: The impacts of the COVID-19 pandemic on food and nutrition insecurity are likely to be significant for Small Island Developing States due to their high dependence on foreign tourism, reliance on imported foods and underdeveloped local food production systems. SIDS are already experiencing high rates of nutrition-related death and disability, including double and triple burdens of malnutrition due to unhealthy diets. We consider the potential role for improved local food production to offset the severity of food system shocks in SIDS and identify the need for localized approaches to embrace systems thinking in order to facilitate communication, coordination and build resilience.


title: Elevations of serum cancer biomarkers correlate with severity of COVID‐19

text: In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID‐19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 versus 46.5 ± 14.7, p<0.001), cytokeratin‐19 fragment (CYFRA21‐1) (2.2 ± 0.9 versus 1.9 ± 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 versus 2.1 ± 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 versus 10.5 ± 4.6, p<0.001) and 153 (14.4 ± 8.9 versus 10.1 ± 4.4, p<0.001) in COVID‐19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21‐1 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID‐19 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C‐reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21‐1(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID‐19, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.


title: COVID-19 pandemic and personal protective equipment shortage: protective efficacy comparing masks and scientific methods for respirator reuse

text: Abstract Background and Aims The abrupt outbreak of COVID-19 and its rapid spread over many health care systems in the world led to personal protective equipment (PPE) shortening, which cannot be faced only by the reduction in their consumption nor by the expensive and time-requiring implementation of their production. It is thus necessary to promote PPE rational use, highlighting possible differences in terms of efficacy among them and promoting an effective technique to reuse them. Methods A literature search was performed on PubMed, Scopus, Cochrane database, and Google Scholar and from 25 top cited papers, 15 were selected for relevance and impact. Results Most studies on prior respiratory virus epidemic to date suggest surgical masks not to be inferior compared with N95 respirators in terms of protective efficacy among health care workers. The use of N95 respirators should be then limited in favor of high-risk situations. Concerning respirators reuse, highly energetic short-wave ultraviolet germicidal irradiation (UVGI) at 254 nm was proficiently applied to determine N95 respirators decontamination from viral respiratory agents, but it requires careful consideration of the type of respirator and of the biological target. Conclusions Rational use and successful reuse of respirators can help facing PPE shortening during a pandemic. Further evidences testing UVGI and other decontamination techniques are an unmet need. The definitive answer to pandemic issues can be found in artificial intelligence and deep learning: these groundbreaking modalities could help in identifying high-risk patients and in suggesting appropriate types and use of PPE.


title: Detection of small amounts of human adenoviruses in stools: comparison of a new immuno real-time PCR assay with classical tools

text: Abstract The detection of low virus concentrations in biological matrices, especially stool samples, is facing significant limitations as far as common diagnostic methods (enzyme-linked-immunosorbent assay (ELISA) or quantitative real-time PCR (qPCR)) are considered. Here the development of a new immuno real-time PCR (iPCR) is described and its performance in the detection of human adenoviruses (HAdVs) in spiked stools is compared with those of ELISA and qPCR assays. For the iPCR, detection of the sandwich formed by the complexation of capture antibody-antigen-detection antibody was performed by qPCR thanks to the substitution of peroxydase by a chimeric DNA. This modification increased the detection sensitivity 200-fold compared to ELISA. The direct qPCR results revealed that only 0.3–9.5% of the spiked HAdV were detectable, resulting from important losses of DNA occurring at the extraction step. This step was not necessary in the iPCR workflow, avoiding this drawback. The losses of viral particles occurred at the elution step from the stool only. The recovery rate of the iPCR was thus better and ranged between 21 and 54%. As a result, iPCR enabled the detection of lower virus concentrations in stool samples compared to those detected by ELISA and qPCR. The iPCR could be considered as a ‘hyper sensitive ELISA’ for early detection of HAdV infections, especially in the case of immunocompromised patients after haematopoietic stem cell transplant.


title: Overwhelming COVID-19 Clinical Trials: Call for Prospective Meta-analysis

text: Abstract In response to the COVID-19 pandemic, an overwhelming number of clinical trials have been registered to test a variety of preventive and therapeutic strategies, as comprehensively summarized by Lythgoe and Middleton [1]. Under such an urgent circumstance, the quality of these clinical studies is inevitably of serious concerns. Here, we propose applying prospective meta-analysis approaches to maximize their values, and to minimize research waste and bias of the ongoing and future COVID-19 trials.


title: Modulation of host metabolism as a target of new antivirals

text: Abstract The therapy for chronic hepatitis C (CH–C) started with interferon (IFN) monotherapy in the early 1990s and this therapy was considered effective in about 10% of cases. The present standard therapy of pegylated IFN with ribavirin achieves a sustained virologic response in about 50% of patients. However, about half of the CH–C patients are still at risk of fatal liver cirrhosis and hepatocellular carcinoma. The other significant event in hepatitis C virus (HCV) research has been the development of a cell culture system. The subgenomic replicon system enables robust HCV RNA replication in hepatoma cells. And recently, the complete life cycle of HCV has been achieved using a genotype 2a strain, JFH1. These hallmarks have provided much information about the mechanisms of HCV replication, including information on the host molecules required for the replication. Anti-HCV reagents targeting HCV proteins have been developed, and some of them are now in clinical trials. However, the RNA-dependent RNA polymerase frequently causes mutations in the HCV genome, which lead to the emergence of drug-resistant HCV mutants. Some of the cellular proteins essential for HCV RNA replication have already been discovered using the HCV cell culture system. These host molecules are also candidate targets for antivirals. Here, we describe the recent progress regarding the anti-HCV reagents targeting host metabolism.


title: Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE): Up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer

text: Abstract We investigated the aberrant expression of plasma proteins in patients with pancreatic cancer. High-abundance plasma proteins (albumin, transferrin, haptoglobin, alpha-1-antitrypsin, IgG and IgA) were depleted by use of an immuno-affinity column, and low-abundance ones were separated into five fractions by anion-exchange chromatography. The fractionated plasma proteins were subjected to 2D-DIGE with highly sensitive fluorescent dyes. The quantitative protein expression profiles obtained by 2D-DIGE were compared between two plasma protein mixtures: one from five non-cancer bearing healthy donors and the other from five patients with pancreatic cancer. Among 1200 protein spots, we found that 33 protein spots were differently expressed between the two mixtures; 27 of these were up-regulated and six were down-regulated in cancer. Mass spectrometry and database searching allowed the identification of the proteins corresponding to the gel spots. Up-regulation of leucine-rich alpha-2-glycoprotein (LRG), which has not previously been implicated in pancreatic cancer, was observed. Western blotting with an anti-LRG antibody validated the up-regulation of LRG in an independent series of plasma samples from healthy controls, patients with chronic pancreatitis, and patients with pancreatic cancer. Our results demonstrate the application of a combination of multi-dimensional liquid chromatography with 2D-DIGE for plasma proteomics and suggest the clinical utility of LRG plasma level measurement.


title: Assessing the Impact of a Rapidly Scaled Virtual Urgent Care in New York City During the COVID19 Pandemic

text: Abstract Background The COVID-19 pandemic quickly challenged New York City healthcare systems. Telemedicine has been suggested to manage acute complaints and divert patients from in-person care. Objectives The objective of this study was to describe and assess the impact of a rapidly scaled virtual urgent care during the COVID-19 pandemic. Methods This was a retrospective cohort study of all patients who presented to a virtual urgent care platform over one month during the COVID-19 pandemic surge. We described scaling our telemedicine urgent care capacity, described patient clinical characteristics, assessed for emergency department (ED) referrals, and analyzed post-visit surveys. Results During the study period, a total of 17,730 patients were seen via virtual urgent care. 454 (2.56%) were referred to an ED. The most frequent diagnoses were COVID-19 related or upper respiratory symptoms. Geospatial analysis indicated a wide catchment area. 251 providers were onboarded to the platform; at peak, 62 providers supplied 364 hours of coverage in one day. The average patient satisfaction score was 4.4/5. 2,668 patients (15.05%) responded to the post-visit survey; 1,236 (49.35%) would have sought care in an ED (11.86%) or in-person urgent care (37.49%). Conclusions A virtual urgent care was scaled to manage a volume of more than 800 patients a day across a large catchment area during the pandemic surge. About half of patients would have otherwise presented to an ED or urgent care in-person. Virtual urgent care is an option for appropriate patients while minimizing in-person visits during the COVID-19 pandemic.


title: Biodiversity, traditional medicine and public health: where do they meet?

text: Given the increased use of traditional medicines, possibilities that would ensure its successful integration into a public health framework should be explored. This paper discusses some of the links between biodiversity and traditional medicine, and addresses their implications to public health. We explore the importance of biodiversity and ecosystem services to global and human health, the risks which human impacts on ecosystems and biodiversity present to human health and welfare.


title: Développement professionnel continu (DPC) et émergence de la recertification en France. Évolution législative et commentaires()

text: Continuing medical education (CME) is an obligation in France. The evaluation of professional practices joined in 2004 the obligation to acquire knowledge, becoming the Continuing professional development (CPD) in 2009. Currently, the system is complete: definition, organization and validation. However, the individual obligation to validate the CPD has never been applied. The recertification process provided for by the 2019 law will not be operational until 2021, at the earliest. Its essential pillar is CPD. The recertification mission who prepared the law excludes all knowledge verification tests. Recertification is done by promoting the professional career path including, in addition to CPD, a maintained and regular activity, an improvement in the relationship with the patient, taking into account the doctor's health and the absence of undesirable events. Seeing that the French Medical Council oversees the professional skills of physicians, it is the Council that receives the validation of the CPD and will receive that of recertification.


title: Etiology of fever in Ugandan children: identification of microbial pathogens using metagenomic next-generation sequencing and IDseq, a platform for unbiased metagenomic analysis

text: Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. We built and employed IDseq, a cloud-based, open access, bioinformatics platform and service to identify microbes from metagenomic next-generation sequencing of tissue samples. In this pilot study, we evaluated blood, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common pathogens identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from blood; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. Among other potential pathogens, we identified one novel orthobunyavirus, tentatively named Nyangole virus, from the blood of a child diagnosed with malaria and pneumonia, and Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis. We also identified two novel human rhinovirus C species. This exploratory pilot study demonstrates the utility of mNGS and the IDseq platform for defining the molecular landscape of febrile infectious diseases in resource limited areas. These methods, supported by a robust data analysis and sharing platform, offer a new tool for the surveillance, diagnosis, and ultimately treatment and prevention of infectious diseases.


44 Impact of Respiratory Virus Infection before Hematopoietic Cell Transplantation (HCT) on Post-Transplant Outcomes in Adults in the PCR Era: Do Rhinovirus and Coronavirus Infections Matter?


title: Rapid outbreak response requires trust

text: As the international community responds to an outbreak of coronavirus-induced pneumonia in Wuhan, China, early and open data sharing — which are vital for its control — depend on the trust that the data will not be used without proper attribution to those who generated it.


title: Cell Entry of C3 Exoenzyme from Clostridium botulinum

text: Clostridium botulinum C3 is the prototype of C3-like ADP-ribosyltransferases that selectively ADP-ribosylate the small GTP-binding proteins RhoA/B/C and inhibit their downstream signaling pathways. It is used as pharmacological tool to study cellular Rho functions. In addition, C3bot harbors a transferase-independent activity on neurons to promote axonal and dendritic growth and branching. Many bacterial protein toxins interact specifically with proteins and/or other membrane components at the surface of target cells. Binding enables access to the appropriate cellular compartment so that the knowledge of the receptor allows essential insight into the mechanism of these toxins. Unlike other bacterial protein toxins (such as the clostridial C1 and C2 toxins from C. botulinum), C3 exoenzyme is devoid of a binding and translocation domain, with which toxins usually initiate receptor-mediated endocytosis followed by access to the intact cell. To date, no specific mechanism for internalization of C3 exoenzyme has been identified. Recently, vimentin was identified as membranous C3-binding partner involved in binding and uptake of C3. Although vimentin is not detected in neurons, vimentin is re-expressed after damage in regenerating neurons. Reappearance of vimentin allows C3 to get access to lesioned neurons/axons to exhibit axonotrophic and dentritotrophic effects.


title: Synthesis and subcellular localization of the murine coronavirus nucleocapsid protein

text: Abstract The synthesis and processing of the nucleocapsid protein (pp60) of the JHM strain of murine coronaviruses were examined. Pulse-chase experiments showed that pp60 was synthesized initially as a protein of approximately 57,000 in molecular weight (p57). Immunoprecipitation using mouse anti-JHMV antiserum indicated that p57 was virus specific. Immunoprecipitation with monoclonal antibodies specific for pp60 showed that p57 was antigenically related to pp60 and was not phosphorylated, while the intracellular protein that comigrated with the virion nucleocapsid protein, pp60, was phosphorylated. The p57 was found exclusively in the cytosol while the majority of pp60 was associated with the membrane fraction but pp60 was not an integral membrane protein.


title: Understanding the neurotropic characteristics of SARS-CoV-2: from neurological manifestations of COVID-19 to potential neurotropic mechanisms

text: Coronavirus disease 2019 (COVID-19), a disease caused by the novel betacoronavirus (SARS-CoV-2), has become a global pandemic threat. The potential involvement of COVID-19 in central nervous system (CNS) has attracted considerable attention due to neurological manifestations presented throughout the disease process. In addition, SARS-CoV-2 is structurally similar to SARS-CoV, and both bind to the angiotensin-converting enzyme 2 (ACE2) receptor to enter human cells. Thus, cells expressing ACE2, such as neurons and glial cells may act as targets and are thus vulnerable to SARS-CoV-2 infection. Here, we have reviewed the neurological characteristics of COVID-19 and summarized possible mechanisms of SARS-CoV-2 invasion of the CNS. COVID-19 patients have presented with a number of different neurological symptoms such as headache, dizziness, hyposmia, and hypogeusia during the course of illness. It has also been reported recently that some cases of COVID-19 have presented with concurrent acute cerebrovascular disease (acute ischemic stroke, cerebral venous sinus thrombosis, cerebral hemorrhage, subarachnoid hemorrhage), meningitis/encephalitis, acute necrotizing hemorrhagic encephalopathy, and acute Guillain–Barré syndrome. Furthermore, SARS-CoV-2 RNA detected in a cerebrospinal fluid specimen of a patient with COVID-19 have provided direct evidence to support the theory of neurotropic involvement of SARS-CoV-2. However, the underlying neurotropic mechanisms of SARS-CoV-2 are yet to be established. SARS-CoV-2 may affect CNS through two direct mechanisms (hematogenous dissemination or neuronal retrograde dissemination) or via indirect routes. The underlying mechanisms require further elucidation in the future.


title: RNA Virus Reverse Genetics and Vaccine Design

text: RNA viruses are capable of rapid spread and severe or potentially lethal disease in both animals and humans. The development of reverse genetics systems for manipulation and study of RNA virus genomes has provided platforms for designing and optimizing viral mutants for vaccine development. Here, we review the impact of RNA virus reverse genetics systems on past and current efforts to design effective and safe viral therapeutics and vaccines.


title: Sharing experiences from a reference laboratory in the public health response for Ebola viral disease, MERS-CoV and H7N9 influenza virus investigations

text: Abstract An efficient public health preparedness and response plan for infectious disease management is important in recent times when emerging and exotic diseases that hitherto were not common have surfaced in countries with potential to spread outside borders. Stewardship from a reference laboratory is important to take the lead for the laboratory network, to proactively set up disease surveillance, provide referral diagnostic services, on-going training and mentorship and to ensure coordination of an effective laboratory response. In Malaysia, the Institute for Medical Research has provided the stewardship for the Ministry of Health's laboratory network that comprises of hospital pathology, public health and university laboratories. In this paper we share our experiences in recent infectious disease outbreak investigations as a reference laboratory within the Ministry of Health infectious disease surveillance network.


title: A cross-classified and multiple membership Cox model applied to calf mortality data

text: Abstract A cross-classified and multiple membership Cox model was applied to calf mortality data from Western Canada, where 23,409 calves from 174 herds were followed for up to 180 days after calving. The herds were cross-classified by 49 veterinary clinics and 9 ecological regions and in a multiple membership relation to the veterinary clinics, resulting in a 3-level cross-classified and multiple membership data structure. The model was formulated in a mixed-effects Poisson model framework with normally distributed random effects, and was fitted to the data by Bayesian Markov Chain Monte Carlo (MCMC) estimation. Important fixed effects included whether the calf was a twin, calf gender, assistance at calving, cow age, average temperature the first week after calving, the percentage of the herd that had already calved, whether calf shelters were provided, whether cow-calf pairs were moved to a nursery area, and whether any animals were purchased into the herd at or near the time of calving. The analysis demonstrated a greater variation among herds than among both ecological regions and veterinary clinics. Further, a simulation study for a setting similar to the real data gave evidence that the used approach provides valid estimates.


title: Arterial Thromboembolism Associated with COVID-19 and elevated D-Dimer levels

text: The novel coronavirus 2019 (SARS-CoV-2) was first identified in January 2020 and has since evolved into a pandemic affecting over 200 countries. The severity of presentation is variable and carries a mortality between 1% and 3%. We continue to learn about the virus and the resulting acute respiratory illness, and hypercoagulability; however, much remains unknown. In our early experience in a high-volume center, we report a series of four cases of acute peripheral arterial ischemia in patients with COVID-19, in the setting of elevated D-dimer levels.


title: Central nervous system manifestations of COVID-19: A systematic review

text: Abstract Objective In this systematic review, we will discuss the evidence on the occurrence of central nervous system (CNS) involvement and neurological manifestations in patients with COVID-19. Methods MEDLINE (accessed from PubMed) and Scopus from December 01, 2019 to March 26, 2020 were systematically searched for related published articles. In both electronic databases, the following search strategy was implemented and these key words (in the title/abstract) were used: “COVID 19” OR “coronavirus” AND “brain” OR “CNS” OR “neurologic”. Results Through the search strategy, we could identify two articles about neurological involvement by COVID-19. One of these publications was a narrative review and the other one was a viewpoint. However, the authors scanned the reference lists of the included studies and could identify multiple references. One study, specifically investigated the neurological manifestations of COVID-19 and could document CNS manifestations in 25% of the patients. Most of the studies investigated the manifestations of COVID-19 in general. Conclusion While neurological manifestations of COVID-19 have not been studied appropriately, it is highly likely that some of these patients, particularly those who suffer from a severe illness, have CNS involvement and neurological manifestations. Precise and targeted documentation of neurological symptoms, detailed clinical, neurological, and electrophysiological investigations of the patients, attempts to isolate SARS-CoV-2 from cerebrospinal fluid, and autopsies of the COVID-19 victims may clarify the role played by this virus in causing neurological manifestations.


title: Proteomic analysis of the response of porcine adrenal gland to heat stress

text: Abstract Heat stress (HS) and its associated pathologies are major challenges facing the pig industry in southern China, and are responsible for large economic losses. However, the molecular mechanisms governing the abnormal secretion of HS-responsive hormones, such as glucocorticoids, are not fully understood. The goal of this study was to investigate differentially expressed proteins (DEPs) in the adrenal glands of pigs, and to elucidate changes in the immune neuroendocrine system in pigs following HS. Through a functional proteomics approach, we identified 1202 peptides, corresponding to 415 proteins. Of these, we found 226 DEPs between heat-stressed and control porcine adrenal gland tissue; 99 of these were up-regulated and 127 were down-regulated in response to HS. These DEPs included proteins involved in substrate transport, cytoskeletal changes, and stress responses. Ingenuity Pathway Analysis was used to identify the subcellular characterization, functional pathway involvement, regulatory networks, and upstream regulators of the identified proteins. Functional network and pathway analyses may provide insights into the complexity and dynamics of HS-host interactions, and may accelerate our understanding of the mechanisms of HS.


title: Perovskite-Silicon Tandems Edge Forward

text: Crystalline silicon (c-Si) photovoltaics dominate the global solar cell market and will continue to do so in the absence of a major, commercially ready technological breakthrough. Emerging photovoltaic materials have the opportunity to augment silicon in a tandem configuration, where two or more solar cells are connected to more efficiently harvest sunlight. Recently in Science, Xu et al. and Hou et al. reported parallel processes to realize high-efficiency monolithic perovskite/c-Si tandems.


title: The complete sequence of the bovine torovirus genome

text: Abstract Viruses in the family Coronaviridae have elicited new interest, with the outbreaks caused by SARS-HCoV in 2003 and the recent discovery of a new human coronavirus, HCoV-NL63. The genus Torovirus, within the family Coronaviridae, is less well characterized, in part because toroviruses cannot yet be grown in cell culture (except for the Berne virus). In this study, we determined the sequence of the complete genome of Breda-1 (BoTV-1), a bovine torovirus. This is the first complete torovirus genome sequence to be reported. BoTV-1 RNA was amplified using long RT-PCR and the amplicons sequenced. The genome has a length of 28.475kb and consisted mainly of the replicase gene (∼20.2kb) which contains two large overlapping ORFs, ORF1a and ORF1b, encoding polyproteins pp1a and pp1b, respectively. Sequence analysis identified conserved domains within the predicted sequences of pp1a and pp1b. Sequence alignments and protein secondary structure prediction data suggest the presence of a 3C-like serine protease domain with similarity to the arterivirus 3C-like serine protease and a single papain-like cysteine protease domain with similarity to the picornavirus leader protease. The ADRP (APPR-1″) domain – unique to the Coronaviridae – was also located in BoTV pp1a. In addition, several hydrophobic domains were identified that are typical of a nidovirus replicase. Within the pp1b sequence the polymerase and helicase domains were identified, as well as sequences predicted to be involved in ribosomal frameshifting, including the conserved slippery sequence UUUAAAC and two potential pseudoknot structures.


title: Metal–Peptide Complexes as Promising Antibiotics to Fight Emerging Drug Resistance: New Perspectives in Tuberculosis

text: In metal-peptide interactions, cations form stable complexes through bonds with coordinating groups as side chains of amino acids. These compounds, among other things, exert a wide variety of antimicrobial activities through structural changes of peptides upon metal binding and redox chemistry. They exhibit different mechanisms of action (MOA), including the modification of DNA/RNA, protein and cell wall synthesis, permeabilization and modulation of gradients of cellular membranes. Nowadays, the large increase in antibiotic resistance represents a crucial problem to limit progression at the pandemic level of the diseases that seemed nearly eradicated, such as tuberculosis (Tb). Mycobacterium tuberculosis (Mtb) is intrinsically resistant to many antibiotics due to chromosomal mutations which can lead to the onset of novel strains. Consequently, the maximum pharmaceutical effort should be focused on the development of new therapeutic agents and antimicrobial peptides can represent a valuable option as a copious source of potential bioactive compounds. The introduction of a metal center can improve chemical diversity and hence specificity and bioavailability while, in turn, the coordination to peptides of metal complexes can protect them and enhance their poor water solubility and air stability: the optimization of these parameters is strictly required for drug prioritization and to obtain potent inhibitors of Mtb infections with novel MOAs. Here, we present a panoramic review of the most recent findings in the field of metal complex-peptide conjugates and their delivery systems with the potential pharmaceutical application as novel antibiotics in Mtb infections.


title: Extreme temperature event and mass mortality of insectivorous bats

text: A mass mortality event involving Chaerephon plicatus and Taphozous theobaldi bats occurred during a heat wave in April 2016 in Cambodia. This was investigated to clarify the causes of the die-off and assess the risk to public health. Field evidences, clinical signs, and gross pathology findings were consistent with a heat stress hypothesis. However, the detection of a novel bat paramyxovirus raises questions about its role as a contributing factor or a coincidental finding. Systematic documentation of bat die-offs related to extreme weather events is necessary to improve understanding of the effect of changing weather patterns on bat populations and the ecosystem services they provide.


title: Clinical Course of COVID‐19 in a Liver Transplant Recipient on Hemodialysis and Response to Tocilizumab Therapy: A Case Report

text: The novel coronavirus disease 2019 (COVID‐19) is a highly infectious and rapidly spreading disease. There are limited published data on the epidemiology and outcomes of COVID‐19 infection among organ transplant recipients. After initial flulike symptoms, progression to an inflammatory phase may occur, characterized by cytokine release rapidly leading to respiratory and multiorgan failure. We report the clinical course and management of a liver transplant recipient on hemodialysis, who presented with COVID‐19 pneumonia, and despite completing a 5‐day course of hydroxychloroquine, later developed marked inflammatory manifestations with rapid improvement after administration of off‐label, single‐dose tocilizumab. We also highlight the role of lung ultrasonography in early diagnosis of the inflammatory phase of COVID‐19. Future investigation of the effects of immunomodulators among transplant recipients with COVID‐19 infection will be important.


title: Mixed infections with Chlamydia and porcine epidemic diarrhea virus - a new in vitro model of chlamydial persistence

text: BACKGROUND: Chlamydiae induce persistent infections, which have been associated with a wide range of chronic diseases in humans and animals. Mixed infections with Chlamydia and porcine epidemic diarrhea virus (PEDV) may result in generation of persistent chlamydial infections. To test this hypothesis, an in vitro model of dual infection with cell culture-adapted PEDV and Chlamydia abortus or Chlamydia pecorum in Vero cells was established. RESULTS: Infected cultures were investigated by immunofluorescence (IF), transmission electron microscopy (TEM) and re-infection experiments. By IF, Chlamydia-infected cells showed normal inclusions after 39 hpi. Dual infections with Chlamydia abortus revealed a heterogenous mix of inclusion types including small inclusions consisting of aberrant bodies (ABs), medium-sized inclusions consisting of ABs and reticulate bodies and normal inclusions. Only aberrant inclusions were observable in dual infection experiments with Chlamydia pecorum and PEDV. TEM examinations of mixed infections with Chlamydia abortus and Chlamydia pecorum revealed aberrant chlamydial inclusions containing reticulate-like, pleomorphic ABs, which were up to 2 μm in diameter. No re-differentiation into elementary bodies (EBs) was detected. In re-infection experiments, co-infected cells produced fewer EBs than monoinfected cells. CONCLUSIONS: In the present study we confirm that PEDV co-infection alters the developmental cycle of member species of the family Chlamydiaceae, in a similar manner to other well-described persistence induction methods. Interestingly, this effect appears to be partially species-specific as Chlamydia pecorum appears more sensitive to PEDV co-infection than Chlamydia abortus, as evidenced by TEM and IF observations of a homogenous population of aberrant inclusions in PEDV - Chlamydia pecorum co-infections.


title: The Importance of Advancing SARS-CoV-2 Vaccines in Children

text: While the role of children in the chain of transmission of SARS-CoV-2 remains to be fully defined, they likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2; thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection or ‘herd immunity’, we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.


title: Identification of a pH sensor in Influenza hemagglutinin using X-ray crystallography

text: Abstract Hemagglutnin (HA) mediates entry of influenza virus through a series of conformational changes triggered by the low pH of the endosome. The residue or combination of residues acting as pH sensors has not yet been fully elucidated. In this work, we assay pH effects on the structure of H5 HA by soaking HA crystallized at pH 6.5 in a series of buffers with lower pH, mimicking the conditions of the endosome. We find that HA1-H38, which is conserved in Group 1 HA, undergoes a striking change in side chain conformation, which we attribute to its protonation and cation-cation repulsion with conserved HA1-H18. This work suggests that x-ray crystallography can be applied for studying small-scale pH-induced conformational changes providing valuable information on the location of pH sensors in HA. Importantly, the observed change in HA1-H38 conformation is further evidence that the pH-induced conformational changes of HA are the result of a series of protonation events to conserved and non-conserved pH sensors.


Awaiting the “catharsis”


title: Simultaneous detection of respiratory viruses in children with acute respiratory infection using two different multiplex reverse transcription-PCR assays

text: Abstract A 4-tube multiplex RT-PCR (mRT-PCR), which showed higher sensitivity over conventional methods, was previously developed for the diagnosis of 14 viral pathogens of the respiratory tract. Herein the mRT-PCR was compared to the commercial Luminex mPCR-microsphere flow cytometry assay (Resplex II) which allows the detection of 12 different viruses. Eleven different viruses were identified in 91 nasopharyngeal swabs of children with acute respiratory infection, influenza A (IAV) and B, respiratory syncytial virus (RSV), human rhinovirus (hRhV), human echovirus, parainfluenza viruses (PIV) 1, 2, 3 and 4, human metapneumovirus (hMPV), and human coronavirus NL63. The results of the two techniques showed 53 and 40 positive patients by the Resplex II assay and mRT-PCR, respectively, with a concordance in 35 positive and 33 negative patients (74.7%). Individual RT-PCR tests were performed to control viruses not simultaneously detected by the two multiplex assays. The major virus misdiagnosed by mRT-PCR was IAV whereas the major viruses misdiagnosed by Resplex II were PIV1, 3 and 4. The mRT-PCR remains a simple, rapid, and specific assay for the specific detection of respiratory viruses, and can be easily implemented with standards in clinical laboratories at a low cost.


title: Database resources of the National Center for Biotechnology Information

text: The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank(®) nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 39 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Data Management, RefSeq Functional Elements, genome data download, variation services API, Magic-BLAST, QuickBLASTp, and Identical Protein Groups. Resources that were updated in the past year include the genome data viewer, a human genome resources page, Gene, virus variation, OSIRIS, and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.


title: Human Coronavirus in Hospitalized Children With Respiratory Tract Infections: A 9-Year Population-Based Study From Norway

text: BACKGROUND: The burden of human coronavirus (HCoV)-associated respiratory tract infections (RTIs) in hospitalized children is poorly defined. We studied the occurrence and hospitalization rates of HCoV over 9 years. METHODS: Children from Sør-Trøndelag County, Norway, hospitalized with RTIs and asymptomatic controls, were prospectively enrolled from 2006 to 2015. Nasopharyngeal aspirates were analyzed with semiquantitative polymerase chain reaction (PCR) tests for HCoV subtypes OC43, 229E, NL63, and HKU1, and 13 other respiratory pathogens. RESULTS: HCoV was present in 9.1% (313/3458) of all RTI episodes: 46.6% OC43, 32.3% NL63, 16.0% HKU1, and 5.8% 229E. Hospitalization rates for HCoV-positive children with lower RTIs were 1.5 and 2.8 per 1000 <5 and <1 years of age, respectively. The detection rate among controls was 10.2% (38/373). Codetections occurred in 68.1% of the patients and 68.4% of the controls. In a logistic regression analysis, high HCoV genomic loads (cycle threshold <28 in PCR analysis) were associated with RTIs (odds ratio = 3.12, P = .016) adjusted for relevant factors. CONCLUSIONS: HCoVs occurred in 1 of 10 hospitalized children with RTIs and asymptomatic controls. A high HCoV genomic load was associated with RTI. HCoVs are associated with a substantial burden of RTIs in need of hospitalization.


title: Cordyceps – A traditional Chinese medicine and another fungal therapeutic biofactory?

text: Abstract Traditional Chinese medicines (TCM) are growing in popularity. However, are they effective? Cordyceps is not studied as systematically for bioactivity as another TCM, Ganoderma. Cordyceps is fascinating per se, especially because of the pathogenic lifestyle on Lepidopteron insects. The combination of the fungus and dead insect has been used as a TCM for centuries. However, the natural fungus has been harvested to the extent that it is an endangered species. The effectiveness has been attributed to the Chinese philosophical concept of Yin and Yang and can this be compatible with scientific philosophy? A vast literature exists, some of which is scientific, although others are popular myth, and even hype. Cordyceps sinensis is the most explored species followed by Cordyceps militaris. However, taxonomic concepts were confused until a recent revision, with undefined material being used that cannot be verified. Holomorphism is relevant and contamination might account for some of the activity. The role of the insect has been ignored. Some of the analytical methodologies are poor. Data on the “old” compound cordycepin are still being published: ergosterol and related compounds are reported despite being universal to fungi. There is too much work on crude extracts rather than pure compounds with water and methanol solvents being over-represented in this respect (although methanol is an effective solvent). Excessive speculation exists as to the curative properties. However, there are some excellent pharmacological data and relating to apoptosis. For example, some preparations are active against cancers or diabetes which should be fully investigated. Polysaccharides and secondary metabolites are of particular interest. The use of genuine anamorphic forms in bioreactors is encouraged.


title: COVID‐19 and outbreak of chilblains: are they related?

text: SARS‐CoV‐2 is a new coronavirus that causes COVID‐19, a disease associated with severe pneumonia.1 Many other clinical manifestations have been associated with the disease (diarrhoea, anosmia, dysgeusia, etc.) and patients can be healthy carriers of the virus.2 Several dermatologic manifestations associated with COVID‐19 have been reported.3 Among them are numerous cases of chilblain‐like lesions (CBLL) in young patients in good general condition, often not tested, or tested negative, for the SARS‐CoV‐2.4,5 In a recent study on 375 Spanish patients with suspected or confirmed COVID‐19, these CBLL accounted for 19% of all cutaneous lesions;3 they were observed in young patients with mild systemic symptoms and seemed to appear late in the course of the disease.


title: Virus entry: molecular mechanisms and biomedical applications

text: Viruses have evolved to enter cells from all three domains of life — Bacteria, Archaea and Eukaryotes. Of more than 3,600 known viruses, hundreds can infect human cells and most of those are associated with disease. To gain access to the cell interior, animal viruses attach to host-cell receptors. Advances in our understanding of how viral entry proteins interact with their host-cell receptors and undergo conformational changes that lead to entry offer unprecedented opportunities for the development of novel therapeutics and vaccines.


title: Optimization of in vitro growth conditions for enterotropic murine coronavirus strains

text: Abstract Enterotropic mouse hepatitis virus (MHV) strains have been difficult to grow in cell culture. In an attempt to develop an efficient in vitro cultivation system for enterotropic MHV strains (MHV-RI and MHV-Y), 8 murine cell lines were inoculated with MHV-RI- or MHV-Y-infected infant mouse intestinal homogenates and screened for the production of cytopathic effects. MHV-RI and MHV-Y consistently produced cytopathic effects only in J774A.1 cells. Both strains produced titers of 106 TCID50/ml in subsequent passages in J774.1 cells. MHV strains -1, -3, -A59, -JHM, -S and -DVIM also produced high-titer viral stocks in J774A.1 cells. Therefore J774A.1 cells are the first cells found that support the replication of these 8 enterotropic and respiratory MHV strains. After passage in J774A.1 cells, MHV-RI and MHV-Y could infect previously non-susceptible cell lines (17C1-1, CMT-93, N18 and NCTC 1469), though cytopathic effects were often negligible with MHV-RI. MHV-Y, but not MHV-RI, grew in L2(Percy) cells. Using L2(Percy) cells, an agarose overlay and Giemsa staining, MHV-Y could be quantified by plaque assay. Infant mouse bioassays, plaque assays and cell culture infections were compared for their sensitivity in detecting MHV-Y in infected intestinal homogenates and cell supernatants.


title: Host adaptive immunity deficiency in severe pandemic influenza

text: INTRODUCTION: Pandemic A/H1N1/2009 influenza causes severe lower respiratory complications in rare cases. The association between host immune responses and clinical outcome in severe cases is unknown. METHODS: We utilized gene expression, cytokine profiles and generation of antibody responses following hospitalization in 19 critically ill patients with primary pandemic A/H1N1/2009 influenza pneumonia for identifying host immune responses associated with clinical outcome. Ingenuity pathway analysis 8.5 (IPA) (Ingenuity Systems, Redwood City, CA) was used to select, annotate and visualize genes by function and pathway (gene ontology). IPA analysis identified those canonical pathways differentially expressed (P < 0.05) between comparison groups. Hierarchical clustering of those genes differentially expressed between groups by IPA analysis was performed using BRB-Array Tools v.3.8.1. RESULTS: The majority of patients were characterized by the presence of comorbidities and the absence of immunosuppressive conditions. pH1N1 specific antibody production was observed around day 9 from disease onset and defined an early period of innate immune response and a late period of adaptive immune response to the virus. The most severe patients (n = 12) showed persistence of viral secretion. Seven of the most severe patients died. During the late phase, the most severe patient group had impaired expression of a number of genes participating in adaptive immune responses when compared to less severe patients. These genes were involved in antigen presentation, B-cell development, T-helper cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination. Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia, along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and IL-1ra) in serum. CONCLUSIONS: Our findings suggest an impaired development of adaptive immunity in the most severe cases of pandemic influenza, leading to an unremitting cycle of viral replication and innate cytokine-chemokine release. Interruption of this deleterious cycle may improve disease outcome.


Symposia and Oral Presentations


Smoking Habit and Hospitalization for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Related Pneumonia: the unsolved paradox behind the evidence.


title: Polycystic kidney disease in a Chartreux cat

text: Polycystic kidney disease (PKD) is one of the most common genetic diseases in cats. It has been widely described in Persians and Persian-related cats and sporadically in other breeds. The purpose of the present paper is to describe the first reported case of PKD in a 12-year-old female Chartreux cat. The cat was referred with polyuria and polydipsia and enlarged and irregular kidneys at palpation. Multiple renal cysts and a single liver cyst were identified by ultrasound and the inherited pattern was confirmed by genetic test (polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assay). Chartreux cats should be included in the screening programme of PKD, and PKD should be always considered as a possible cause of chronic renal failure in this breed.


title: Decoupling for ecological sustainability: A categorisation and review of research literature

text: The idea of decoupling “environmental bads” from “economic goods” has been proposed as a path towards sustainability by organizations such as the OECD and UN. Scientific consensus reports on environmental impacts (e.g., greenhouse gas emissions) and resource use give an indication of the kind of decoupling needed for ecological sustainability: global, absolute, fast-enough and long-enough. This goal gives grounds for a categorisation of the different kinds of decoupling, with regard to their relevance. We conducted a survey of recent (1990–2019) research on decoupling on Web of Science and reviewed the results in the research according to the categorisation. The reviewed 179 articles contain evidence of absolute impact decoupling, especially between CO2 (and SOX) emissions and evidence on geographically limited (national level) cases of absolute decoupling of land and blue water use from GDP, but not of economy-wide resource decoupling, neither on national nor international scales. Evidence of the needed absolute global fast-enough decoupling is missing.


Deep Impact of COVID-19 in the HealthCare of Latin America: the case of Brazil


title: Activation of Interleukin-32 Pro-Inflammatory Pathway in Response to Influenza A Virus Infection

text: BACKGROUND: Interleukin (IL)-32 is a recently described pro-inflammatory cytokine that has been reported to be induced by bacteria treatment in culture cells. Little is known about IL-32 production by exogenous pathogens infection in human individuals. METHODS AND FINDINGS: In this study, we found that IL-32 level was increased by 58.2% in the serum samples from a cohort of 108 patients infected by influenza A virus comparing to that of 115 healthy individuals. Another pro-inflammatory factor cyclooxygenase (COX)-2-associated prostaglandin E2 was also upregulated by 2.7-fold. Expression of IL-32 in influenza A virus infected A549 human lung epithelial cells was blocked by either selective COX-2 inhibitor NS398 or Aspirin, a known anti-inflammatory drug, indicating IL-32 was induced through COX-2 in the inflammatory cascade. Interestingly, we found that COX-2-associate PGE(2) production activated by influenza virus infection was significantly suppressed by over-expression of IL-32 but increased by IL-32-specific siRNA, suggesting there was a feedback mechanism between IL-32 and COX-2. CONCLUSIONS: IL-32 is induced by influenza A virus infection via COX-2 in the inflammatory cascade. Our results provide that IL-32 is a potential target for anti-inflammatory medicine screening.


title: Biowarfare, Bioterrorism and Biocrime: a historical overview on microbial harmful applications

text: Microbial Forensics is a field that continues to grow in interest and application among the forensic community. This review, divided into two sections, covers several topics associated with this new field. The first section presents a historic overview concerning the use of microorganisms (or its product, i.e. toxins) as harmful biological agents in the context of biological warfare (biowarfare), bioterrorism, and biocrime. Each case is illustrated with the examination of case reports that span from prehistory to the present day. The second part of the manuscript is devoted to the role of MF and highlights the necessity to prepare for the pressing threat of the harmful use of biological agents as weapons. Preventative actions, developments within the field to ensure a timely and effective response and are discussed herein.


title: Oral Delivery of Probiotics Expressing Dendritic Cell-Targeting Peptide Fused with Porcine Epidemic Diarrhea Virus COE Antigen: A Promising Vaccine Strategy against PEDV

text: Porcine epidemic diarrhea virus (PEDV), an enteric coronavirus, is the causative agent of porcine epidemic diarrhea (PED) that damages intestinal epithelial cells and results in severe diarrhea and dehydration in neonatal suckling pigs with up to 100% mortality. The oral vaccine route is reported as a promising approach for inducing protective immunity against PEDV invasion. Furthermore, dendritic cells (DCs), professional antigen-presenting cells, link humoral and cellular immune responses for homeostasis of the intestinal immune environment. In this study, in order to explore an efficient oral vaccine against PEDV infection, a mucosal DC-targeting oral vaccine was developed using Lactobacillus casei to deliver the DC-targeting peptide (DCpep) fused with the PEDV core neutralizing epitope (COE) antigen. This probiotic vaccine could efficiently elicit secretory immunoglobulin A (SIgA)-based mucosal and immunoglobulin G (IgG)-based humoral immune responses via oral vaccination in vivo. Significant differences (p < 0.05) in the immune response levels were observed between probiotics expressing the COE-DCpep fusion protein and COE antigen alone, suggesting better immune efficiency of the probiotics vaccine expressing the DC-targeting peptide fused with PEDV COE antigen. This mucosal DC-targeting oral vaccine delivery effectively enhances vaccine antigen delivery efficiency, providing a useful strategy to induce efficient immune responses against PEDV infection.


title: Ultrastructural Characterization of Zika Virus Replication Factories

text: A global concern has emerged with the pandemic spread of Zika virus (ZIKV) infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs). Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER) membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton.


title: Modeling epidemic spread with awareness and heterogeneous transmission rates in networks

text: During an epidemic outbreak in a human population, susceptibility to infection can be reduced by raising awareness of the disease. In this paper, we investigate the effects of three forms of awareness (i.e., contact, local, and global) on the spread of a disease in a random network. Connectivity-correlated transmission rates are assumed. By using the mean-field theory and numerical simulation, we show that both local and contact awareness can raise the epidemic thresholds while the global awareness cannot, which mirrors the recent results of Wu et al. The obtained results point out that individual behaviors in the presence of an infectious disease has a great influence on the epidemic dynamics. Our method enriches mean-field analysis in epidemic models.


title: Talaromyces marneffei laboratory cross reactivity with Histoplasma and Blastomyces urinary antigen

text: Abstract Talaromyces marneffei is a fungal opportunistic infection usually seen in immunocompromised patients from eastern countries. In the US when examining HIV-patients for suspected fungal infections, laboratory serological tests guide therapy until cultures are available. We present the case of a 35-year-old HIV patient originally from Thailand in which urine lab results were positive for Blastomyces and Histoplasma antigen, but biopsy showed T. marneffei. Concomitantly the patient presented with hyponatremia which was deemed to be from SIADH. We present the first case of a patient with T. marneffei cross reactivity with Blastomyces, Histoplasma and SIADH due to pulmonary disease.


title: Chapter 9 Safety of Water Used in Food Production

text: Abstract Water has a major and fundamental role in safety of food production. It is a critical resource for the food industry with wide uses. In most of the food preparation and processing operations, water is often taken for granted. Water is very commonly used in food production at various levels, apart from being used as an ingredient. Water quality and its impact on food products and various operations in food industries are often underestimated. Such underestimation often leads to mismanagement of water, equipment operation and maintenance issues, loss of revenue, food safety, and product quality. This chapter deals with several aspects of water as applicable to the food production. Agriculture is the largest consumer of water, requiring over 100 times more than that used for personal needs. The concept of water footprint is used to discern the importance of relative value in terms of water. The water footprint of any animal product is larger than the water footprint of a wisely chosen crop product with equivalent nutritional value. The production of meat requires between 6 and 20 times more water than for cereals and vegetables or fruits. Water is indispensible in cleaning and sanitization in food production, which is an integral part in processing operations in food production. In food storage and preservation, water plays a key role. The water activity of food helps a great deal in deciding shelf-life and food safety. The quality of water is the fundamental consideration in any food production process. The quality depends on the source of water and the actual application in food production. The pollution of water occurs at any stage in various ways. Physical, chemical, or biological agents cause significant health hazards in safe production of food. Contamination of water by several pathological microorganisms creates major challenges in food safety and threats to human and animal health. The majority of diseases which are transmitted through contaminated fresh water, are caused by pathogenic microorganisms. Whenever water is used as an ingredient in food product, it must be free from undesirable taste, odor, color, and impurities, including pathogenic organisms that could jeopardize consumers’ health and gravely affect product quality. The quality of water must adhere to the safe drinking water standard. Various techniques and methods of water treatments should be used to purify water as per the guidelines of government authorities to improve food safety. Soil has multiple roles in deciding water quality. Good quality soil has better ability to remove all types of contaminants of water, whereas deteriorated soil becomes a source of heavy metals, organic chemicals, and soil pathogens in water contamination. Use of genetically modified food is gaining much publicity recently. Even though a controversial topic, great care must be taken when genetically modified food is used. It is mandatory that one should review the basic principles of food safety before consuming any food.


title: From fighting COVID-19 pandemic to tackling sustainable development goals: An opportunity for responsible information systems research

text: The recent outbreak of the COVID-19 pandemic has posed a significant threat to the healthy lives and well-being of billions of people worldwide. As the world begins to open up from lockdowns and enters an unprecedented state of vulnerability, or what many have called “the new normal”, it makes sense to reflect on what we have learned, revisit our fundamental assumptions, and start charting the way forward to contribute to building a sustainable world. In this essay, we argue that despite its significant damage to human lives and livelihoods, the coronavirus pandemic presents an excellent opportunity for the human family to act in solidarity and turn this crisis into an impetus to achieve the United Nation’s (UN) Sustainable Development Goals (SDG). In this article, we will highlight the six relevant themes that have evolved during the pandemic and the corresponding topics that future researchers could focus on. We conclude by issuing a call for more research attention on tackling SDG through developing the concept and practice of digital sustainability.


title: Detection of transmissible gastroenteritis virus by RT-PCR and differentiation from porcine respiratory coronavirus

text: Abstract An RT-PCR method was developed that amplified genetic material from the 5′ end of the S protein gene of both transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV), but discriminated between the two by the size of the product generated. A number of restriction endonuclease enzymes were assessed for recognition of the amplicons so produced. The assay was shown to detect viral RNA from all of the 26 different TGEV and PRCV isolates examined, covering a period from 1946 to 1996. Detection of TGEV in clinical specimens was possible using a spin column method to extract RNA and sensitivity was compared to virus isolation and antigen detection ELISA. The method could provide a means of confirming positive results from immunological screening tests such as FAT and ELISA, reducing the need for virus isolation and convalescent serology.


title: Pathogenesis of flavivirus encephalitis

text: Publisher Summary Within the flavivirus family, viruses that cause natural infections of the central nervous system (CNS) principally include members of the Japanese encephalitis virus (JEV) serogroup and the tick-borne encephalitis virus (TBEV) serocomplex. The pathogenesis of diseases involves complex interactions of viruses, which differ in neurovirulence potential, and a number of host factors, which govern susceptibility to infection and the capacity to mount effective antiviral immune responses both in the periphery and within the CNS. This chapter summarizes progress in the field of flavivirus neuropathogenesis. Mosquito-borne and tickborne viruses are considered together. Flavivirus neuropathogenesis involves both neuroinvasiveness (capacity to enter the CNS) and neurovirulence (replication within the CNS), both of which can be manipulated experimentally. Neuronal injury as a result of bystander effects may be a factor during flavivirus neuropathogenesis given that microglial activation and elaboration of inflammatory mediators, including IL-1β and TNF-α, occur in the CNS during these infections and may accompany the production of nitric oxide and peroxynitrite, which can cause neurotoxicity.