title: Chapter 39 Microbial Forensics: Educating the Workforce and the Community

text: Publisher Summary Disciplines related to microbial forensics are evolving rapidly. This evolution includes technology, analytical capabilities, and, equally as important, education and training. The scientific bases, applications, interpretations, and lessons learned by those who have been intimately involved in the early years of microbial forensics need to be documented and transferred to the next generation of scientists and decision makers so that we can protect society from potential harm resulting from bioterrorism and biocrime. The burgeoning field of microbial forensics should be accompanied by a parallel development of educational infrastructure and resources targeted at the next generation of practitioners, as well as diverse elements for the policy, research, and law enforcement communities. A microbial forensics education program can be broad, providing information encompassing all aspects of the field from science to policy, or more focused depending on its purpose and target audience. Policy makers must have a general understanding of microbial forensics results and better appreciation of their implications in order to effect sound and defensible policy decisions. Finally, an important group that informs the public and government is the news media. They are frequently the primary interface between the scientist and the public, making their observations, insights, or inaccuracies of great importance and impact. Educational efforts will better prepare such individuals to be informed and responsible and must be varied in depth and scope to match the target audience of various entities involved in microbial forensics.


title: Avian flu (H5N1): its epidemiology, prevention, and implications for anesthesiology

text: Abstract Avian flu, influenza A subtype H5N1, is an emergent and virulent disease that poses a threat to the health and safety of the world community. Avian flu is 1 of more than 25 influenza A viruses that reside primarily in birds but also infect humans and other mammals. Avian flu is responsible for the current outbreak in Asia; H5N1 has now displayed probable human-to-human transmission; it could be a harbinger of a global epidemic. Anesthesiologists are exposed to a risk for infection when they are involved in airway instrumentation of infected patients. Given the evidence of emerging resistance to common antiviral agents used to treat H5N1 influenza virus and limited supply of H5N1 vaccine, prevention is our best protection. The following article will detail the virology and preventive public health practices for H5N1. This knowledge can also be used to define and prevent other yet unidentified infectious threats.


title: Telbivudine preserves T‐helper 1 cytokine production and downregulates programmed death ligand 1 in a mouse model of viral hepatitis

text: Summary. Telbivudine is an orally bioavailable L‐nucleoside with potent and specific anti‐hepatitis B virus activity. The higher rate of hepatitis B e antigen (HBeAg) seroconversion during telbivudine treatment than other potent anti‐HBV agents suggests a potential immunomodulatory effect. We sought to determine the effects of telbivudine on the immune system, particularly on cytokine production and T‐cell response, using an animal model with mouse hepatitis virus strain 3 (MHV‐3)‐induced hepatitis. The effects of telbivudine on virus replication and cytokine production were investigated in vitro using MHV‐3‐infected macrophages, and the effects on T‐cell response were investigated in vivo in an MHV‐3‐induced viral hepatitis model. Telbivudine had no effect on MHV‐3 replication in macrophages. However, the production of tumour necrosis factor‐α and interleukin‐12 was increased significantly in MHV‐3‐induced macrophages treated with telbivudine. In vivo survival was enhanced in telbivudine‐treated mice, with marked normalization in clinical conditions and histological lesions. Serum levels of interferon‐γ were elevated significantly after telbivudine treatment in MHV‐3‐infected C3H mice. In contrast, serum interleukin‐4 levels were decreased significantly. Furthermore, telbivudine treatment enhanced the ability of T cells to undergo proliferation and secrete cytokines but did not affect cytotoxicity of infected hepatocytes. Of note, we found that telbivudine treatment suppressed programmed death ligand 1 expression on T cells. The results demonstrate the immunomodulatory properties of telbivudine, independent of its antiviral activity, in a mouse model of MHV‐3‐induced hepatitis.


title: ISG15, a Small Molecule with Huge Implications: Regulation of Mitochondrial Homeostasis

text: Viruses are responsible for the majority of infectious diseases, from the common cold to HIV/AIDS or hemorrhagic fevers, the latter with devastating effects on the human population. Accordingly, the development of efficient antiviral therapies is a major goal and a challenge for the scientific community, as we are still far from understanding the molecular mechanisms that operate after virus infection. Interferon-stimulated gene 15 (ISG15) plays an important antiviral role during viral infection. ISG15 catalyzes a ubiquitin-like post-translational modification termed ISGylation, involving the conjugation of ISG15 molecules to de novo synthesized viral or cellular proteins, which regulates their stability and function. Numerous biomedically relevant viruses are targets of ISG15, as well as proteins involved in antiviral immunity. Beyond their role as cellular powerhouses, mitochondria are multifunctional organelles that act as signaling hubs in antiviral responses. In this review, we give an overview of the biological consequences of ISGylation for virus infection and host defense. We also compare several published proteomic studies to identify and classify potential mitochondrial ISGylation targets. Finally, based on our recent observations, we discuss the essential functions of mitochondria in the antiviral response and examine the role of ISG15 in the regulation of mitochondrial processes, specifically OXPHOS and mitophagy.


title: Differential Inhibitory Activities and Stabilisation of DNA Aptamers against the SARS Coronavirus Helicase

text: The helicase from severe acute respiratory syndrome coronavirus (SARS‐CoV) possesses NTPase, duplex RNA/DNA‐unwinding and RNA‐capping activities that are essential for viral replication and proliferation. Here, we have isolated DNA aptamers against the SARS‐CoV helicase from a combinatorial DNA library. These aptamers show two distinct classes of secondary structure, G‐quadruplex and non‐G‐quadruplex, as shown by circular dichroism and gel electrophoresis. All of the aptamers that were selected stimulated ATPase activity of the SARS‐CoV helicase with low‐nanomolar apparent K (m) values. Intriguingly, only the non‐G‐quadruplex aptamers showed specific inhibition of helicase activities, whereas the G‐quadruplex aptamers did not inhibit helicase activities. The non‐G‐quadruplex aptamer with the strongest inhibitory potency was modified at the 3′‐end with biotin or inverted thymidine, and the modification increased its stability in serum, particularly for the inverted thymidine modification. Structural diversity in selection coupled to post‐selection stabilisation has provided new insights into the aptamers that were selected for a helicase target. These aptamers are being further developed to inhibit SARS‐CoV replication.


title: Fever in travellers returning from the tropics

text: Abstract The increase in international travel, the growing presence of arbovirus vectors in our country, and notifications of haemorrhagic fever such as the current outbreak of Ebola in D.R. Congo and the cases of Crimea-Congo haemorrhagic fever in our country have again cast the spotlight on tropical diseases. Isolating suspected cases of highly contagious and lethal diseases must be a priority (haemorrhagic fever, MERS-CoV). Assessing the patient, taking a careful medical history based on epidemiological aspects of the area of origin, activities they have carried out, their length of stay in the area and the onset of symptoms, will eventually help us, if not to make a definitive diagnosis, at least to exclude diseases that pose a threat to these patients. Malaria should be ruled out because of its frequency, without forgetting other common causes of fever familiar to emergency doctors.


title: The 2b protein as a minor structural component of PRRSV

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) ORF2 contains an internal ORF that codes for a small non-glycosylated protein known as 2b. Previous work had identified the presence of a 10kDa 2b protein in virus-infected cells and the induction of an anti-2b response in PRRSV-infected pigs, as well as a possible association of 2b with the virion (Wu et al., 2001, Virology 287:183–191). In this study, we utilized two experimental approaches, including the use of a 2b peptide-specific monoclonal antibody, to demonstrate that the PRRSV 2b protein is an integral component of the PRRSV virion. This study suggests that 2b in PRRSV is similar to the E protein in EAV and forms a minor structural component of the virion.


title: A key role for the carboxy-terminal tail of the murine coronavirus nucleocapsid protein in coordination of genome packaging

text: Abstract The prototype coronavirus mouse hepatitis virus (MHV) exhibits highly selective packaging of its genomic positive-stranded RNA into assembled virions, despite the presence in infected cells of a large excess of subgenomic viral mRNAs. One component of this selectivity is the MHV packaging signal (PS), an RNA structure found only in genomic RNA and not in subgenomic RNAs. It was previously shown that a major determinant of PS recognition is the second of the two RNA-binding domains of the viral nucleocapsid (N) protein. We have now found that PS recognition additionally depends upon a segment of the carboxy-terminal tail (domain N3) of the N protein. Since domain N3 is also the region of N protein that interacts with the membrane (M) protein, this finding suggests a mechanism by which selective genome packaging is accomplished, through the coupling of genome encapsidation to virion assembly.


Saudi Arabia`s measures to curb the COVID-19 outbreak: temporary suspension of the Umrah pilgrimage


title: Studying Human Pathogens in Animal Models: Fine Tuning the Humanized Mouse

text: Humanized mice are crucial tools for studying human pathogens in systemic situations. An animal model of human coronavirus infectious disease has been generated by gene transfer of the human receptor for virus-cell interaction (aminopeptidase N, APN, CD13) into mice. We showed that in vitro and in vivo infections across the species barrier differ in their requirements. Transgenic cells were susceptible to human coronavirus HCoV-229E infection demonstrating the requirement of hAPN for viral cell entry. Transgenic mice, however, could not be infected suggesting additional requirements for in vivo virus susceptibility. Crossing hAPN transgenic mice with interferon unresponsive Stat1(−/− )mice resulted in markedly enhanced virus replication in vitro but did not result in detectable virus replication in vivo. Adaptation of the human virus to murine cells led to successful infection of the humanized transgenic mice. Future genetic engineering approaches are suggested to provide animal models for the better understanding of human infectious diseases.


title: Guidelines for communicating about bats to prevent persecution in the time of COVID-19

text: While the current COVID-19 pandemic continues to wreak havoc on human health and national economies, conservationists are struggling to prevent misguided persecution of bats, which are misleadingly being blamed for spreading the disease. Although at a global level, such persecution is relatively uncommon, even a few misguided actions have the potential to cause irrevocable damage to already vulnerable species. Here, we draw on the latest findings from psychology, to explain why some conservation messaging may be reinforcing misleading negative associations. We provide guidelines to help ensure that conservation messaging is working to neutralize dangerous and unwarranted negative-associations between bats and disease-risk. We provide recommendations around three key areas of psychological science: (i) debunking misinformation; (ii) counteracting negative associations; and (iii) changing harmful social norms. We argue that only by carefully framing accurate, honest, and duly contextualized information, will we be able to best serve society and present an unbiased perspective of bats. We hope this guidance will help conservation practitioners and researchers to develop effective message framing strategies that minimize zoonotic health risks and support biodiversity and its associated ecosystem services.


title: Early Respiratory Viral Acquisition after Allogeneic Hematopoietic Cell Transplant (HCT)

text: Introduction Respiratory infections after HCT lead to significant morbidity, mortality, and health care costs due to pulmonary complications. In up to a third of patients following allogeneic HCT, infection can progress from an upper to a lower respiratory tract infection. Without vaccines or effective therapeutics for most viruses, very little can be done beyond supportive care. Objectives There is a need to identify risk factors for virus acquisition in HCT recipients in order to develop and implement better preventative interventions. Methods In a prospective study, 471 HCT patients enrolled between 2005 and 2010 underwent weekly PCR-based surveillance for RSV, metapneumovirus, parainfluenza virus 1-4, influenza A and B, rhinovirus, coronavirus, and adenovirus. Detailed weekly surveys were collected from subjects for up to 1 year post-transplant on symptoms and exposures to children under 10 years or sick contacts (within 3 feet for more than 1 hour total in the past week). We performed multivariable Cox regression analysis to identify risk factors associated with the time to first positive respiratory viral detection by PCR (asymptomatic and symptomatic) within the first 100 days HCT. Results In this cohort, 211 patients (45%) acquired a respiratory virus in the first 100 days after transplant. Of those infected, 88 (42%) were symptomatic with at least 2 respiratory symptoms. We found significantly higher risk of acquiring any respiratory viral infection for patients with underlying chronic leukemia compared with other hematologic malignancies [hazard ratio (HR) 1.79 (1.16 – 2.77)], exposure to children under or over 4 years [HR 1.84 (1.36 – 2.48)], exposure to contacts with cold symptoms [HR 1.47 (1.02 – 2.12)], exposure to systemic steroids [HR 1.49 (1.07 – 2.08)], and absolute monocyte counts < 100/µL [HR 1.81 (1.12 – 2.94)]. Age, age of child exposure, gender, smoking history, season, conditioning regimen, donor relationship, cell source, presence of acute GVHD, albumin level, total IgG level, lymphocyte counts, and neutrophil counts were not associated with risk for acquisition. We also analyzed the association of these same variables with the time to first positive respiratory viral detection with symptomatic respiratory disease. We found that exposure to children [HR 1.56 (1.03 – 2.35)] and exposure to steroids [HR 1.59 (1.01 – 2.52)] remained associated with acquisition of symptomatic respiratory viral infection. Conclusions These data support the contribution of both exposure and immunologic determinants to the risk of respiratory viral acquisition with and without development of symptoms. Although many infections were asymptomatic, patients receiving steroids and those in close proximity to children may benefit from closer monitoring and counseling in the early post-transplant period.


Pets in Voluntary Household Quarantine


title: SICE: an improved missing data imputation technique

text: In data analytics, missing data is a factor that degrades performance. Incorrect imputation of missing values could lead to a wrong prediction. In this era of big data, when a massive volume of data is generated in every second, and utilization of these data is a major concern to the stakeholders, efficiently handling missing values becomes more important. In this paper, we have proposed a new technique for missing data imputation, which is a hybrid approach of single and multiple imputation techniques. We have proposed an extension of popular Multivariate Imputation by Chained Equation (MICE) algorithm in two variations to impute categorical and numeric data. We have also implemented twelve existing algorithms to impute binary, ordinal, and numeric missing values. We have collected sixty-five thousand real health records from different hospitals and diagnostic centers of Bangladesh, maintaining the privacy of data. We have also collected three public datasets from the UCI Machine Learning Repository, ETH Zurich, and Kaggle. We have compared the performance of our proposed algorithms with existing algorithms using these datasets. Experimental results show that our proposed algorithm achieves 20% higher F-measure for binary data imputation and 11% less error for numeric data imputations than its competitors with similar execution time.


title: Responses of Chinese Elderly to the Threat of Severe Acute Respiratory Syndrome (SARS) in a Canadian Community

text: ABSTRACT Objective: To describe responses of Chinese elderly living in Edmonton, Canada, during the severe acute respiratory syndrome (SARS) pandemic, and their use of Western and/or traditional Chinese medicine. Design: A QUAL‐qual mixed method design, using grounded theory as the core method and ethnographic strategies are used to inform the cultural aspects of the study. Sample: A purposeful sample of 19 Chinese elderly was interviewed and tape recorded. Four traditional Chinese Practitioners were also interviewed. Methods: The interviews were transcribed and analyzed in Chinese and later translated into English. Data analysis utilized the constant comparison method. Results: Participants experienced a 5‐stage process of protecting self, family, and others, responding according to the perceived threat of SARS. Participants used both Western and traditional Chinese strategies to combat SARS. Their desire to protect others took precedence under the moral code of filial piety. Once SARS was under control, the community remained vigilant and continued to monitor for its possible reoccurrence. Conclusions: Cultural beliefs and practices within the Chinese population support the recommendations set by the health department for the protection of individuals and the community during the SARS pandemic. Therefore, the public health sector should become familiar with and support these Chinese cultural networks during pandemics.


title: Impact of Respiratory Virus Infections in Exacerbation of Acute and Chronic Rhinosinusitis

text: Rhinosinusitis (RS) is a symptomatic disease classification of many causes and is a major economic burden worldwide. It is widely accepted that RS is further classified into acute (ARS) and chronic (CRS) rhinosinusitis based on the duration of the symptoms, and that viral infection plays a large role in initiating or potentiating the disease. In this review, we examine the role of respiratory virus infection in the exacerbation of ARS and CRS. We explore the epidemiology of viral exacerbation of ARS and CRS and highlight key viruses that may cause exacerbation. We also review the current understanding of viral infections in the upper airway to further explain the putative underlying mechanisms of inflammatory events in ARS and CRS exacerbation. Advances in accurate diagnosis of the etiologic respiratory viruses of ARS and CRS symptoms which can lead to better disease management are also surveyed. In addition to the current treatments which provide symptomatic relief, we also explore the potential of harnessing existing antiviral strategies to prevent ARS and CRS exacerbation, especially with improved viral diagnostic tools to guide accurate prescription of antivirals against causative respiratory viruses.


title: Covid-19, Adverse Scrutiny and The Journey to Code: where next for biometric tech?

text: Between leaving a Big Four accountancy firm on New Year's Eve and joining DWF Law as head of data protection and cyber-security, I spent a month developing a new business plan – fine-tuning a number of ideas I'd been working on concerning the future of data protection and privacy. This time allowed me to confirm the business plan should focus on two core ideas: namely ‘Adverse Scrutiny’ and ‘The Journey to Code'.


title: Adaptations to the British Society of Gastroenterology guidelines on the management of acute severe UC in the context of the COVID-19 pandemic: a RAND appropriateness panel

text: OBJECTIVE: Management of acute severe UC (ASUC) during the novel COVID-19 pandemic presents significant dilemmas. We aimed to provide COVID-19-specific guidance using current British Society of Gastroenterology (BSG) guidelines as a reference point. DESIGN: We convened a RAND appropriateness panel comprising 14 gastroenterologists and an IBD nurse consultant supplemented by surgical and COVID-19 experts. Panellists rated the appropriateness of interventions for ASUC in the context of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Median scores and disagreement index (DI) were calculated. Results were discussed at a moderated meeting prior to a second survey. RESULTS: Panellists recommended that patients with ASUC should be isolated throughout their hospital stay and should have a SARS-CoV-2 swab performed on admission. Patients with a positive swab should be discussed with COVID-19 specialists. As per BSG guidance, intravenous hydrocortisone was considered appropriate as initial management; only in patients with COVID-19 pneumonia was its use deemed uncertain. In patients requiring rescue therapy, infliximab with continuing steroids was recommended. Delaying colectomy because of COVID-19 was deemed inappropriate. Steroid tapering as per BSG guidance was deemed appropriate for all patients apart from those with COVID-19 pneumonia in whom a 4–6 week taper was preferred. Post-ASUC maintenance therapy was dependent on SARS-CoV-2 status but, in general, biologics were more likely to be deemed appropriate than azathioprine or tofacitinib. Panellists deemed prophylactic anticoagulation postdischarge to be appropriate in patients with a positive SARS-CoV-2 swab. CONCLUSION: We have suggested COVID-19-specific adaptations to the BSG ASUC guideline using a RAND panel.


title: Optimal control application to an Ebola model

text: Abstract Ebola virus is a severe, frequently fatal illness, with a case fatality rate up to 90%. The outbreak of the disease has been acknowledged by World Health Organization as Public Health Emergency of International Concern. The threat of Ebola in West Africa is still a major setback to the socioeconomic development. Optimal control theory is applied to a system of ordinary differential equations which is modeling Ebola infection through three different routes including contact between humans and a dead body. In an attempt to reduce infection in susceptible population, a preventive control is put in the form of education and campaign and two treatment controls are applied to infected and late-stage infected (super) human population. The Pontryagins maximum principle is employed to characterize optimality control, which is then solved numerically. It is observed that time optimal control is existed in the model. The activation of each control showed a positive reduction of infection. The overall effect of activation of all the controls simultaneously reduced the effort required for the reduction of the infection quickly. The obtained results present a good framework for planning and designing cost-effective strategies for good interventions in dealing with Ebola disease. It is established that in order to reduce Ebola threat all the three controls must be taken into consideration concurrently.


title: A20 (Tnfaip3) Deficiency in Myeloid Cells Protects against Influenza A Virus Infection

text: The innate immune response provides the first line of defense against viruses and other pathogens by responding to specific microbial molecules. Influenza A virus (IAV) produces double-stranded RNA as an intermediate during the replication life cycle, which activates the intracellular pathogen recognition receptor RIG-I and induces the production of proinflammatory cytokines and antiviral interferon. Understanding the mechanisms that regulate innate immune responses to IAV and other viruses is of key importance to develop novel therapeutic strategies. Here we used myeloid cell specific A20 knockout mice to examine the role of the ubiquitin-editing protein A20 in the response of myeloid cells to IAV infection. A20 deficient macrophages were hyperresponsive to double stranded RNA and IAV infection, as illustrated by enhanced NF-κB and IRF3 activation, concomitant with increased production of proinflammatory cytokines, chemokines and type I interferon. In vivo this was associated with an increased number of alveolar macrophages and neutrophils in the lungs of IAV infected mice. Surprisingly, myeloid cell specific A20 knockout mice are protected against lethal IAV infection. These results challenge the general belief that an excessive host proinflammatory response is associated with IAV-induced lethality, and suggest that under certain conditions inhibition of A20 might be of interest in the management of IAV infections.


title: Estimates of the initial impact of the COVID-19 epidemic on overall mortality: evidence from Italy

text: This study provides evidence of the enormous death toll attributable to COVID-19 https://bit.ly/2X4C6a8


title: Codon adaptation biases among sylvatic and urban genotypes of Dengue virus type 2

text: Abstract Dengue virus (DENV) emerged from the sylvatic environment and colonized urban settings, being sustained in a human-Aedes-human transmission chain, mainly by the bites of females of the anthropophilic species Aedes aegypti. Herein, we sought evidence for fine-tuning in viral codon usage, possibly due to viral adaptation to human transmission. We compared the codon adaptation of DENV serotype 2 (DENV-2) genotypes from urban and sylvatic habitats and tried to correlate the findings with key evolutionary determinants. We found that DENV-2 codons of urban and sylvatic genotypes had a higher CAI to humans than to Ae. aegypti. Remarkably, we found no significant differences in codon adaptation to human between urban American/Asian and sylvatic DENV-2 genotypes. Moreover, CAI values were significantly different, when comparing all genotypes to Ae. aegypti codon preferences, with lower values for sylvatic than urban genotypes. In summary, our findings suggest the presence of a molecular signature among the genotypes that circulate in sylvatic and urban environments, and may help explain the trafficking of DENV-2 strains to an urban cycle.


title: Harnessing in vivo siRNA delivery for drug discovery and therapeutic development

text: The use of RNA interference (RNAi) is spreading rapidly to nearly every aspect of biomedical research. The gene silencing capability of RNAi is being used to study individual gene's biological function and role in biochemical pathways. However, the efficacy of RNAi depends upon efficient delivery of the intermediates of RNAi, short interfering RNA (siRNA) and short hairpin RNA (shRNA) oligonucleotides. The delivery challenge is even greater when the aim is to inhibit the expression of target genes in animal models. Although i n vivo delivery of siRNA is complicated and challenging, recent results are encouraging. In this review, the latest developments of in vivo delivery of siRNA and the crucial issues related to this effort are addressed.


Acute respiratory tract infection leads to procoagulant changes in human subjects


title: Swabbing for respiratory viral infections in older patients: a comparison of rayon and nylon flocked swabs

text: The purpose of this study was to compare the sampling efficacy of rayon swabs and nylon flocked swabs, and of oropharyngeal and nasopharyngeal specimens for the detection of respiratory viruses in elderly patients. Samples were obtained from patients 60 years of age or above who were newly admitted to Sorlandet Hospital Arendal, Norway. The patients were interviewed for current symptoms of a respiratory tract infection. Using rayon swabs and nylon flocked swabs, comparable sets of mucosal samples were harvested from the nasopharynx and the oropharynx. The samples were analysed using real-time polymerase chain reaction (PCR) methods. A total of 223 patients (mean age 74.9 years, standard deviation [SD] 9.0 years) were swabbed and a virus was recovered from 11% of the symptomatic patients. Regardless of the sampling site, a calculated 4.8 times higher viral load (95% confidence interval [CI] 1.3–17, p = 0.017) was obtained using the nylon flocked swabs as compared to the rayon swabs. Also, regardless of the type of swab, a calculated 19 times higher viral load was found in the samples from the nasopharynx as compared to the oropharynx (95% CI 5.4–67.4, p < 0.001). When swabbing for respiratory viruses in elderly patients, nasopharyngeal rather than oropharyngeal samples should be obtained. Nylon flocked swabs appear to be more efficient than rayon swabs.


title: Exploitation of glycosylation in enveloped virus pathobiology

text: Glycosylation is a ubiquitous post-translational modification responsible for a multitude of crucial biological roles. As obligate parasites, viruses exploit host-cell machinery to glycosylate their own proteins during replication. Viral envelope proteins from a variety of human pathogens including HIV-1, influenza virus, Lassa virus, SARS, Zika virus, dengue virus, and Ebola virus have evolved to be extensively glycosylated. These host-cell derived glycans facilitate diverse structural and functional roles during the viral life-cycle, ranging from immune evasion by glycan shielding to enhancement of immune cell infection. In this review, we highlight the imperative and auxiliary roles glycans play, and how specific oligosaccharide structures facilitate these functions during viral pathogenesis. We discuss the growing efforts to exploit viral glycobiology in the development of anti-viral vaccines and therapies.


title: Prothrombotic antiphospholipid antibodies in COVID-19

text: Patients with coronavirus disease 19 (COVID-19) are at high risk for thrombotic arterial and venous occlusions. At the same time, lung histopathology often reveals fibrin-based occlusion of small vessels in patients who succumb to the disease. Antiphospholipid syndrome (APS) is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies (aPL) targeting phospholipids and phospholipid-binding proteins. Small case series have recently detected aPL in patients with COVID-19. Here, we measured eight types of aPL (anticardiolipin IgG/IgM/IgA, anti-beta-2 glycoprotein I IgG/IgM/IgA, and anti- phosphatidylserine/prothrombin (PS/PT) IgG/IgM) in the sera of 172 patients hospitalized with COVID-19. We detected anticardiolipin IgM antibodies in 23%, anti-PS/PT IgG in 24%, and anti-PS/PT IgM in 18%. Any aPL was present in 52% of patients using the manufacturer's threshold and in 30% using a more stringent cutoff (>40 units). Higher levels of aPL were associated with neutrophil hyperactivity (including the release of neutrophil extracellular traps/NETs), higher platelet count, more severe respiratory disease, and lower glomerular filtration rates. Similar to patients with known and longstanding APS, IgG fractions isolated from patients with COVID-19 promoted NET release from control neutrophils. Furthermore, injection of these COVID-19 IgG fractions into mice accelerated venous thrombosis. Taken together, these studies suggest that a significant percentage of patients with COVID-19 become at least transiently positive for aPL and that these aPL are potentially pathogenic.


title: Assembly of vaccinia virus: role of the intermediate compartment between the endoplasmic reticulum and the Golgi stacks

text: Vaccinia virus, the prototype of the Poxviridae, is a large DNA virus which replicates in the cytoplasm of the host cell. The assembly pathway of vaccinia virus displays several unique features, such as the production of two structurally distinct, infectious forms. One of these, termed intracellular naked virus (INV), remains cells associated while the other, termed extracellular enveloped virus (EEV), is released from the cell. In addition, it has long been believed that INVs acquire their lipid envelopes by a unique example of de novo membrane biogenesis. To examine the structure and assembly of vaccinia virus we have used immunoelectron microscopy using antibodies to proteins of different subcellular compartments as well as a phospholipid analysis of purified INV and EEV. Our data are not consistent with the de novo model of viral membrane synthesis but rather argue that the vaccinia virus DNA becomes enwrapped by a membrane cisterna derived from the intermediate compartment between the ER and the Golgi stacks, thus acquiring two membranes in one step. Phospholipid analysis of purified INV supports its derivation from an early biosynthetic compartment. This unique assembly process is repeated once more when the INV becomes enwrapped by an additional membrane cisterna, in agreement with earlier reports. The available data suggest that after fusion between the outer envelope and the plasma membrane, mature EEV is released from the cell.


title: News

text: Chinese scientists released genetic information on the coronavirus causing an outbreak of SARS-like illness in Wuhan, China The Vaccine Research Institute at the US National Institutes of Health (NIH) immediately began development of a new vaccine After the 2003 SARS outbreak, it took 20 months from the release of the viral genome to get a vaccine ready for human trials The zika virus took six months Now, the NIH is pushing to have a vaccine ready for testing in three to six months The race is on The NIH team took the template for a SARS vaccine and swapped enough code from the new virus to start a new vaccine Researchers, having experience with SARS, already knew which part of the virus to choose for the vaccine’s antigen, a sort of red flag for the immune system This synthetic antigen will prod the body to make antibodies


title: Can the concept of Health Promoting Schools help to improve students' health knowledge and practices to combat the challenge of communicable diseases: Case study in Hong Kong?

text: BACKGROUND: The growing epidemics of emerging infectious diseases has raised the importance of a setting approach and include the Health Promoting School (HPS) framework to promote better health and hygiene. Built on the concept of 'the' HPS framework, the Hong Kong Healthy Schools Award scheme includes "Personal Health Skills" as one of its key aspects to improve student hygiene knowledge and practices. This study examines the differences in student perceptions, knowledge and health behaviours between those schools that have adopted the HPS framework and those that have not adopted. METHODS: A cross-sectional study using multi-stage random sampling was conducted among schools with awards (HSA) and those schools not involved in the award scheme nor adopting the concept of HPS (non-HPS). For HSA group, 5 primary schools and 7 secondary schools entered the study with 510 students and 789 students sampled respectively. For the 'Non-HPS' group, 8 primary schools and 7 secondary schools entered the study with 676 students and 725 students sampled respectively. A self-administered questionnaire was used as the measuring instrument. RESULTS: Students in the HSA category were found to be better with statistical significance in personal hygiene practice, knowledge on health and hygiene, as well as access to health information. HSA schools were reported to have better school health policy, higher degrees of community participation, and better hygienic environment. CONCLUSION: Students in schools that had adopted the HPS framework had a more positive health behaviour profile than those in non-HPS schools. Although a causal relationship is yet to be established, the HPS appears to be a viable approach for addressing communicable diseases.


title: Worry experienced during the 2015 Middle East Respiratory Syndrome (MERS) pandemic in Korea

text: BACKGROUND: Korea failed in its risk communication during the early stage of the Middle East Respiratory Syndrome (MERS) outbreak; consequently, it faced difficulties in managing MERS, while disease-related worry increased. Disease-related worry can help disease prevention and management, but can also have a detrimental effect. This study measured the overall level of disease-related worry during the MERS outbreak period in Korea and the influencing factors and levels of disease-related worry during key outbreak periods. METHODS: The cross-sectional survey included 1,000 adults who resided in Korea. An ordinal logistic regression was performed for the overall level of MERS-related worry, and influencing factors of worry were analyzed. A reliability test was performed on the levels of MERS-related worry during key outbreak periods. RESULTS: The overall level of MERS-related worry was 2.44. Multivariate analysis revealed that women and respondents w very poor subjective health status had higher levels of worry. Respondents with very high stress in daily life had higher levels of worry than those who reported having little stress. The reliability test results on MERS-related worry scores during key outbreak periods showed consistent scores during each period. CONCLUSION: Level of worry increased in cases having higher perceived susceptibility and greater trust in informal information, while initial stage of outbreak was closely associated with that at later stages. These findings suggest the importance of managing the level of worry by providing timely and accurate disease-related information during the initial stage of disease outbreak.


title: Coronavirus Crisis: Government Aid That Also Promotes Employee Ownership

text: The premise of this paper is that state aid to distressed companies should benefit not only the current owners but also the employees, who are the ones taking personal risks to continue or restart companies. Government aid during the Great Recession was aimed primarily at restoring the status quo. In the current deeper crisis, aid should be designed to create a fairer, more inclusive and more socially responsible economy by promoting employee ownership as both an incentive and a reward. We show how the Employee Stock Ownership Plan, which has been pioneered in the US for 40 years and can be adapted to the European legal context, can be used as the vehicle for structuring this aid.


Coronavirus disease and local government


title: Chapter 1 Basic Biology of Oral Microbes

text: Abstract This chapter describes the basic biology of oral microbes, including cytological basis of the microorganisms, microbial morphology, microbial cell structure, microbial physiology, and microbial genetics.


title: Zoonotic Viruses Associated with Illegally Imported Wildlife Products

text: The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.


title: Feasibility and High Quality Measured in the Rapid Expansion of Telemedicine During COVID‐19 for Sports and Musculoskeletal Medicine Practice

text: INTRODUCTION: The global pandemic due to SARS‐CoV‐2 has resulted in an expansion of telemedicine. Measures of quality and barriers for rapid use by patients and physicians are not well described. OBJECTIVE: To describe results from a quality improvement initiative during rapid adoptive phase of telemedicine during the pandemic. DESIGN: Patient and physician satisfaction with synchronous audiovisual telemedicine visits was measured during early adoptive phase (April 6‐17, 2020) within the division of sports medicine in an academic Physical Medicine and Rehabilitation (PM&R) department. Patients were invited to participate in a quality improvement initiative by completing an online survey at the end of a telemedicine visit. Physicians completed a separate survey. PRIMARY OUTCOME MEASURES: Patient measures included visit type, duration of encounter, quality, and satisfaction. Physicians reported on experiences performing telemedicine. RESULTS: Surveys were completed by 119 patients (289 telemedicine encounters, response rate 41%) and 13 physiatrists. Telemedicine was utilized primarily for follow‐up visits (n=74, 70.6%) and most common duration was 15‐29 minutes. Patients rated their telemedicine visit as “excellent” or “very good” across measures (91.6‐95.0%) including addressing concerns, communication, developing a treatment plan, convenience, and satisfaction. Value of completing a future telemedicine visit was measured at 84.9%. Most reported estimated travel time saved in excess of 30 minutes. Rate of no‐show was 2.8%. Most physicians (62%) had no prior experience with telemedicine visits, and most were comfortable performing these visits after completing 1‐4 sessions (69%). Nearly all physicians (92%) rated their telemedicine experience as very good or excellent. The key barrier identified for telemedicine was technical issues. All physicians reported plans to perform telemedicine visits if reimbursement continues. CONCLUSIONS: In summary, rapid expansion of telemedicine during COVID‐19 pandemic was well‐received by a majority of patients and physicians. This suggests feasibility in rapid expansion of telemedicine for other outpatient sports medicine practices. This article is protected by copyright. All rights reserved.


title: Chapter Five Emerging Themes in PDZ Domain Signaling Structure, Function, and Inhibition

text: Abstract Post-synaptic density-95, disks-large and zonula occludens-1 (PDZ) domains are small globular protein–protein interaction domains widely conserved from yeast to humans. They are composed of ∼90 amino acids and form a classical two α-helical/six β-strand structure. The prototypical ligand is the C-terminus of partner proteins; however, they also bind internal peptide sequences. Recent findings indicate that PDZ domains also bind phosphatidylinositides and cholesterol. Through their ligand interactions, PDZ domain proteins are critical for cellular trafficking and the surface retention of various ion channels. In addition, PDZ proteins are essential for neuronal signaling, memory, and learning. PDZ proteins also contribute to cytoskeletal dynamics by mediating interactions critical for maintaining cell–cell junctions, cell polarity, and cell migration. Given their important biological roles, it is not surprising that their dysfunction can lead to multiple disease states. As such, PDZ domain–containing proteins have emerged as potential targets for the development of small molecular inhibitors as therapeutic agents. Recent data suggest that the critical binding function of PDZ domains in cell signaling is more than just glue, and their binding function can be regulated by phosphorylation or allosterically by other binding partners. These studies also provide a wealth of structural and biophysical data that are beginning to reveal the physical features that endow this small modular domain with a central role in cell signaling.


title: Canada's global health role: supporting equity and global citizenship as a middle power

text: Summary Canada's history of nation building, combined with its status as a so-called middle power in international affairs, has been translated into an approach to global health that is focused on equity and global citizenship. Canada has often aspired to be a socially progressive force abroad, using alliance building and collective action to exert influence beyond that expected from a country with moderate financial and military resources. Conversely, when Canada has primarily used economic self-interest to define its global role, the country's perceived leadership in global health has diminished. Current Prime Minister Justin Trudeau's Liberal federal government has signalled a return to progressive values, driven by appreciation for diversity, equality, and Canada's responsibility to be a good global citizen. However, poor coordination of efforts, limited funding, and the unaddressed legacy of Canada's colonisation of Indigenous peoples weaken the potential for Canadians to make meaningful contributions to improvement of global health equity. Amid increased nationalism and uncertainty towards multilateral commitments by some major powers in the world, the Canadian federal government has a clear opportunity to convert its commitments to equity and global citizenship into stronger leadership on the global stage. Such leadership will require the translation of aspirational messages about health equity and inclusion into concrete action at home and internationally.


Editorial: We need more national data on transcatheter aortic valve implantation


title: Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity

text: Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here, we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.


title: Virus discovery and recent insights into virus diversity in arthropods

text: Recent studies on virus discovery have focused mainly on mammalian and avian viruses. Arbovirology with its long tradition of ecologically oriented investigation is now catching up, with important novel insights into the diversity of arthropod-associated viruses. Recent discoveries include taxonomically outlying viruses within the families Flaviviridae, Togaviridae, and Bunyaviridae, and even novel virus families within the order Nidovirales. However, the current focusing of studies on blood-feeding arthropods has restricted the range of arthropod hosts analyzed for viruses so far. Future investigations should include species from other arthropod taxa than Ixodita, Culicidae and Phlebotominae in order to shed light on the true diversity of arthropod viruses.


title: Detection of contaminants in water supply: A review on state-of-the-art monitoring technologies and their applications

text: Abstract Water monitoring technologies are widely used for contaminants detection in wide variety of water ecology applications such as water treatment plant and water distribution system. A tremendous amount of research has been conducted over the past decades to develop robust and efficient techniques of contaminants detection with minimum operating cost and energy. Recent developments in spectroscopic techniques and biosensor approach have improved the detection sensitivities, quantitatively and qualitatively. The availability of in-situ measurements and multiple detection analyses has expanded the water monitoring applications in various advanced techniques including successful establishment in hand-held sensing devices which improves portability in real-time basis for the detection of contaminant, such as microorganisms, pesticides, heavy metal ions, inorganic and organic components. This paper intends to review the developments in water quality monitoring technologies for the detection of biological and chemical contaminants in accordance with instrumental limitations. Particularly, this review focuses on the most recently developed techniques for water contaminant detection applications. Several recommendations and prospective views on the developments in water quality assessments will also be included.


title: Pharmacologic perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19

text: Abstract Coronavirus disease 2019 (COVID-19) caused by a previously unknown pathogen named severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has now become a pandemic threat to the whole world. However, there are no vaccines or specific treatment against the new virus. Therefore, there is an urgent need for advancing novel therapeutic interventions for COVID-19. Glycyrrhizin, a triterpene saponine, is valuable for its various biological functions and pharmacology effects. In this brief article, we will discuss the therapeutic potential of glycyrrhizin for COVID-19 from the perspective of its pharmacological action including binding angiotensin converting enzyme II (ACE2), down-regulating proinflammatory cytokines, inhibiting the accumulation of intracellular ROS, inhibiting thrombin, inhibiting the hyperproduction of airway exudates, and inducing endogenous interferon.


title: How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City

text: The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays.


title: De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection

text: The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.


title: Design, Synthesis and Biological Evaluation of Novel Primaquine-Cinnamic Acid Conjugates of the Amide and Acylsemicarbazide Type

text: In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a–k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a–k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e), benzodioxole (7f), p-Cl (7g) and m-CF(3) (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC(50) = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.


title: Physical Rehabilitation Needs in the BRICS Nations from 1990 to 2017: Cross-National Analyses Using Data from the Global Burden of Disease Study

text: Background: This study analyzes the current and evolving physical rehabilitation needs of BRICS nations (Brazil, Russian Federation, India, China, South Africa), a coalition of large emergent economies increasingly important for global health. Methods: Secondary, cross-national analyses of data on Years Lived with Disability (YLDs) were extracted from the Global Burden of Disease Study 2017. Total physical rehabilitation needs, and those stratified per major condition groups are analyzed for the year 2017 (current needs), and for every year since 1990 (evolution over time). ANOVAs are used to detect significant yearly changes. Results: Total physical rehabilitation needs have increased significantly from 1990 to 2017 in each of the BRICS nations, in every metric analyzed (YLD Counts, YLDs per 100,000 people, and percentage of YLDs relevant to physical rehabilitation; all p < 0.01). Musculoskeletal & pain conditions were leading cause of physical rehabilitation needs across the BRICS nations but to varying degrees: from 36% in South Africa to 60% in Brazil. Country-specific trends include: 25% of South African needs were from HIV-related conditions (no other BRICS nation had more than 1%); India had both absolute and relative growths of pediatric rehabilitation needs (p < 0.01); China had an exponential growth in the per-capita needs from neurological and neoplastic conditions (p < 0.01; r(2) = 0.97); Brazil had a both absolute and relative growth of needs coming from musculoskeletal & pain conditions (p < 0.01); and the Russian Federation had the highest neurological rehabilitation needs per capita in 2017 (over than three times those of India, South Africa or Brazil). Conclusions: total physical rehabilitation needs have been increasing in each of the BRICS nations, both in absolute and relative values. Apart from the common growing trend, each of the BRICS nations had own patterns for the amount, typology, and evolution of their physical rehabilitation needs, which must be taken into account while planning for health and physical rehabilitation programs, policies and resources.


title: Impulsive vaccination and dispersal on dynamics of an SIR epidemic model with restricting infected individuals boarding transports

text: Abstract To understand the effect of impulsive vaccination and restricting infected individuals boarding transports on disease spread, we establish an SIR model with impulsive vaccination, impulsive dispersal and restricting infected individuals boarding transports. This SIR epidemic model for two regions, which are connected by transportation of non-infected individuals, portrays the evolvement of diseases. We prove that all solutions of the investigated system are uniformly ultimately bounded. We also prove that there exists globally asymptotically stable infection-free boundary periodic solution. The condition for permanence is discussed. It is concluded that the approach of impulsive vaccination and restricting infected individuals boarding transports provides reliable tactic basis for preventing disease spread.


title: Acute and late disease induced by murine coronavirus, strain JHM, in a series of recombinant inbred strains between BALB/cHeA and STS/A mice

text: Abstract To examine the genetic control of acute and late disease induced by a murine coronavirus, strain JHM (JHMV), BALB/cHeA, STS/A, F1 hybrids and 13 recombinant inbred (RI) strains between BALB/cHeA and STS/A mouse strains were inoculated intracerebrally with 100 pfu of JHMV. All the BALB/cHeA mice died within 2 weeks from acute encephalitis. In contrast, STS/A mice were shown to be partially resistant, with a mortality rate of 30%, longer survival times and lower rates of viral production. The mortality rates, survival times and viral titers of F1 hybrids and the RI strains varied, suggesting involvement of multiple genes. STS/A, F1 hybrid and RI mice surviving the acute infection occasionally developed severe paraparesis about 1 month post-infection. In these mice, vacuolar degeneration, astrocytosis, the absence of perivascular cuffing and minimal demyelination were found in the central nervous system. No infectious virus could be recovered from these mice. Although the paralysis of delayed onset was limited to STS/A, F1 hybrid and eight of the 13 RI strains, the incidence varied significantly among the RI strains. These results may suggest that JHMV-induced late disease is also under multifactorial control. The pathogenesis of JHMV infection is discussed.


title: Agricultural policy reforms: Roles of markets and states in China and India

text: Abstract Market reforms have been given much of the credit for China's spectacular growth performance. This paper looks at China's reform process systematically with India's and argues that the Chinese state has played a key role in transforming China into a modern economic state, deploying unlimited supplies of labor and combining it with a variety of initiatives in a pragmatic, nonideological way to promote public and private investment and create productive employment in agricultural, manufacturing, and service sectors. India's reforms have been sporadic and are still a work in progress. The record-breaking expansion of China's financial system in fostering investments was overlooked, but has attracted considerable attention in recent years. Is China unique, or are lessons from the Chinese experience for public policy and its sequencing transferrable for agricultural and structural transformation in countries lagging behind, including India?


title: Reproductive Healthcare During a Pandemic: A New York State of Mind

text: The purpose of this Commentary is to assess whether the designation by New York State Department of Health of “sexual and reproductive health services as essential” is consonant with the seemingly divergent objectives of providing patient-centered care and advancing national public health objectives in the resource-constrained setting of a global pandemic.


title: Prevalence of Anxiety and Depression symptom, and the Demands for Psychological Knowledge and Interventions in college students during COVID-19 epidemic: A large Cross-Sectional Study

text: BACKGROUND: : Although studies have suggested experiencing the epidemic of severe infectious diseases increased the prevalence of mental health problems, the association between COVID-19 epidemic and risk of anxiety and depression symptom in college students in China was unclear. METHODS: : A large cross-sectional online survey with 44,447 college students was conducted in Guangzhou, China. The Zung's Self-rating Anxiety Scale (SAS) and the Center for Epidemiologic Studies Depression Scale (CES-D Scale) were used to define the anxiety and depression symptom, respectively. Multivariable logistic regression models were used to analyze the association between COVID-19 epidemic and risk of anxiety and depression symptom. RESULTS: : The prevalence of anxiety and depression symptom was 7.7% (95% confidence interval [CI]: 7.5%, 8.0%) and 12.2% (95%CI: 11.9%, 12.5%), respectively. Compared with students who reported have not infected or suspected cases in family members and relatives, students who reported having confirmed (OR=4.06; 95%CI: 1.62, 10.19; P=0.003), and suspected (OR=2.11; 95%CI: 1.11, 4.00; P=0.023) cases in family members and relatives had higher risk of depression symptom. Additionally, the proportions of students with anxiety and depression symptom reported more demand of psychological knowledge and interventions than those without (P<0.001). LIMITATIONS: : All the data in this study was collected through online questionnaire, and we did not evaluate the reliability and validity. CONCLUSIONS: : The prevalence of anxiety and depression symptom was relatively low in college students, but the COVID-19 epidemic-related factors might be associated with higher depression symptom risk.


title: Porcine epidemic diarrhea virus reduces feed efficiency in nursery pigs

text: Porcine epidemic diarrhea virus (PEDV) infects enterocytes and in nursery pigs, results in diarrhea, anorexia, and reduced performance. Therefore, the objective of this study was to determine how PEDV infection influenced growth performance and repartitioning of amino acids and energy in nursery pigs. A total of 32 barrows and gilts, approximately 1 wk post-wean (BW = 8.46 ± 0.50 kg), and naïve for PEDV were obtained, weighed, and allotted based on sex and BW to one of two treatments: 1) Control, PEDV naïve and 2) PEDV-inoculated (PEDV) with eight pens of two pigs each per treatment. On day post-inoculation (dpi) 0, PEDV pigs were inoculated via intragastric gavage with PEDV isolate (USA/Iowa/18984/2013). Pig and feeder weights were recorded at dpi −7, 0, 5, and 20 in order to calculate ADG, ADFI, and G:F. Eight pigs per treatment were euthanized on dpi 5 and 20, and tissues and blood were collected. At dpi 5, all PEDV pigs were PCR positive for PEDV in feces. Overall, PEDV pigs tended (P < 0.10) to increase ADFI, which resulted in reduced (P < 0.05) feed efficiency. At dpi 5, PEDV pigs had reduced (P < 0.05) villus height and increased (P < 0.05) stem cell proliferation in the jejunum compared with Control pigs. Pigs inoculated with PEDV had increased (P < 0.05) serum haptoglobin and increased insulin-to-glucose ratios compared with Control pigs at dpi 5. Markers of muscle proteolysis were not different (P > 0.05) between treatments within dpi; however, at dpi 5, 20S proteasome activity was increased (P < 0.05) in longissimus dorsi of PEDV pigs compared with Control pigs. Liver and jejunum gluconeogenic enzyme activities were not different (P > 0.05) between treatments within dpi. Overall, PEDV-inoculated pigs did recover the absorptive capacity that was reduced during PEDV infection by increasing proliferation of intestinal stem cells. However, the energy and nutrients needed to recover the epithelium may be originating from available luminal nutrients instead of muscle proteolysis and gluconeogenesis. This study provides insight into the effects of an enteric coronavirus on postabsorptive metabolism in nursery pigs.


title: A New Era in Endothelial Injury Syndromes: Toxicity of CAR-T Cells and the Role of Immunity

text: Immunotherapy with chimeric antigen receptor T (CAR-T cells) has been recently approved for patients with relapsed/refractory B-lymphoproliferative neoplasms. Along with great efficacy in patients with poor prognosis, CAR-T cells have been also linked with novel toxicities in a significant portion of patients. Cytokine release syndrome (CRS) and neurotoxicity present with unique clinical phenotypes that have not been previously observed. Nevertheless, they share similar characteristics with endothelial injury syndromes developing post hematopoietic cell transplantation (HCT). Evolution in complement therapeutics has attracted renewed interest in these life-threatening syndromes, primarily concerning transplant-associated thrombotic microangiopathy (TA-TMA). The immune system emerges as a key player not only mediating cytokine responses but potentially contributing to endothelial injury in CAR-T cell toxicity. The interplay between complement, endothelial dysfunction, hypercoagulability, and inflammation seems to be a common denominator in these syndromes. As the indications for CAR-T cells and patient populations expand, there in an unmet clinical need of better understanding of the pathophysiology of CAR-T cell toxicity. Therefore, this review aims to provide state-of-the-art knowledge on cellular therapies in clinical practice (indications and toxicities), endothelial injury syndromes and immunity, as well as potential therapeutic targets.


title: Infectious Chronic Rhinosinusitis

text: Chronic rhinosinusitis (CRS) is a persistent inflammatory disease that affects a multitude of people worldwide. The pathogenesis of CRS involves many factors including genetics, status of the sinonasal microbiome, infections and environmental influences. Comorbidities associated with CRS include asthma, allergic rhinitis, bronchiectasis and certain kinds of immunodeficiency. CRS can be divided into different subtypes based on endotypes and phenotypes. Infectious CRS is one such category. The etiology of infectious CRS is usually secondary to chronic bacterial infection which commonly begins with a viral upper respiratory tract infection. Humoral antibody deficiencies can underlie difficult-to-treat or recurrent CRS. Infectious CRS can be treated with antimicrobials, topical or oral corticosteroids and nasal saline irrigations. Patients with CRS and humoral immunodeficiency may require an aggressive treatment approach including immunoglobulin replacement therapy. Despite advancements in the field of CRS, targeted therapies and reliable biomarkers are still lacking.


Les biologistes médicaux s’activent en vue des 700 000 tests


title: Application of System Biology to Explore the Association of Neprilysin, Angiotensin-Converting Enzyme 2 (ACE2), and Carbonic Anhydrase (CA) in Pathogenesis of SARS-CoV-2

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appears with common symptoms including fever, dry cough, and fatigue, as well as some less common sysmptoms such as loss of taste and smell, diarrhea, skin rashes and discoloration of fingers. COVID-19 patients may also suffer from serious symptoms including shortness of breathing, chest pressure and pain, as well as loss of daily routine habits, pointing out to a sever reduction in the quality of life. COVID-19 has afftected almost all countries, however, the United States contains the highest number of infection (> 1,595,000 cases) and deaths cases (> 95,000 deaths) in the world until May 21, 2020. Finding an influential treatment strategy against COVID-19 can be facilitated through better understanding of the virus pathogenesis and consequently interrupting the biochemical pathways that the virus may play role in human body as the current reservoir of the virus. RESULTS: In this study, we combined system biology and bioinformatic approaches to define the role of coexpression of angiotensin-converting enzyme 2 (ACE2), neprilysin or membrane metallo-endopeptidase (MME), and carbonic anhydrases (CAs) and their association in the pathogenesis of SARS-CoV-2. The results revealed that ACE2 as the cellular attachment site of SARS-CoV-2, neprilysin, and CAs have a great contribution together in the renin angiotensin system (RAS) and consequently in pathogenesis of SARS-CoV-2 in the vital organs such as respiratory, renal, and blood circulation systems. Any disorder in neprilysin, ACE2, and CAs can lead to increase of CO(2) concentration in blood and respiratory acidosis, induction of pulmonary edema and heart and renal failures. CONCLUSIONS: Due to the presence of ACE2-Neprilysin-CA complex in most of vital organs and as a receptor of COVID-19, it is expected that most organs are affected by SARS-CoV-2 such as inflammation and fibrosis of lungs, which may conversely affect their vital functions, temporary or permanently, sometimes leading to death. Therefore, ACE2-Neprilysin-CA complex could be the key factor of pathogenesis of SARS-CoV-2 and may provide us useful information to find better provocative and therapeutic strategies against COVID-19.


title: Distribution and characteristics of Beilong virus among wild rodents and shrews in China

text: Beilong virus (BeiV), a member of the newly recognized genus Jeilongvirus of family Paramyxoviridae, has been reported with limited geographic and host scopes, only in Hongkong, China and from two rat species. Here, by next-generation sequencing (NGS) on dominant wild small animal species in 4 provinces in China, we obtained a complete sequence of BeiV strain from Rattus norvegicus in Guangdong, neighboring HongKong, China. We then made an expanded epidemiological investigation in 11 provinces to obtain the geographic distribution and genetic features of this virus. Altogether 7168 samples from 2005 animals (1903 rodents, 100 shrews, 2 mustelidaes) that belonged to 33 species of Cricetidae, Muridae, Sciuridae and Dipodidae family of Rodentia, 3 species of Soricidae family of Soricomorpha, 2 species of Mustelidae family of Carnivora were examined by RT-PCR and sequencing. A positive rate of 3.7% (266/7168) was obtained that was detected from 22 animal species, including 5 species of Cricetidae family, 12 species of Muridae family, 2 species of Sciuridae family and 3 species of Soricidae family. Phylogenetic analyses based on 154 partial Large gene sequences grouped the current BeiV into two lineages, that were related to their geographic regions and animal hosts. Our study showed the wide distribution of BeiV in common species of wild rodents and shrews in China, highlighting the necessity of epidemiological study in wider regions.


Centenaire après 50 années de diabète de type 2


title: Organoids – New Models for Host–Helminth Interactions

text: Organoids are multicellular culture systems that replicate tissue architecture and function, and are increasingly used as models of viral, bacterial, and protozoan infections. Organoids have great potential to improve our current understanding of helminth interactions with their hosts and to replace or reduce the dependence on using animal models. In this review, we discuss the applicability of this technology to helminth infection research, including strategies of co-culture of helminths or their products with organoids and the challenges, advantages, and drawbacks of the use of organoids for these studies. We also explore how complementing organoid systems with other cell types and components may allow more complex models to be generated in the future to further investigate helminth–host interactions.


title: Two-Stage DEA in Banks: Terminological Controversies and Future Directions()

text: Given the importance that two-stage Data Envelopment Analysis (DEA) models have attained in recent years, this paper presents a systematic review of the literature on the topic focusing on the banking industry. We discuss the two-stage terminology itself, which is not yet not consolidated. We also discuss the current state-of-the-art and present opportunities, as well as challenges, for future studies. We analyse 59 papers, divided them into ten classes that cover various perspectives of two stage DEA studies, such as the economic context, geographic region of the banking units, methodological characteristics, and type of the models, either internal or external. Additionally, we investigate several controversial points regarding two-stage DEA models, such as the variable selection approach, the technique used in the second stage, and the possible impact of non-discretionary variables on efficiency. Results of the literature review indicate the lack of a uniform or universal terminology for two-stage DEA models in the baking industry. Moreover, the main objective of most papers involves extending or improving DEA models. Radial models, with variable returns of scale, and the intermediation approach are the most frequent configurations. Finally, we identify seven gaps in the literature for both internal and external two-stage DEA models and two specific gaps to external ones.Each gap is discussed in depth in the text and can be considered opportunities for future studies.


title: Treating Leukemia in the Time of COVID-19

text: The coronavirus disease 2019 (COVID-19) pandemic poses several challenges to the management of patients with leukemia. The biology of each leukemia and its corresponding treatment with conventional intensive chemotherapy, with or without targeted therapies (venetoclax, FLT3 inhibitors, IDH1/2 inhibitors, Bruton's tyrosine kinase inhibitors), introduce additional layers of complexity during COVID-19 high-risk periods. The knowledge about COVID-19 is accumulating rapidly. An important distinction is the prevalence of “exposure” versus “clinical infectivity,” which determine the risk versus benefit of modifying potentially highly curative therapies in leukemia. At present, the rate of clinical infection is <1–2% worldwide. With a mortality rate of 1–5% in COVID-19 patients in the general population and potentially of >30% in patients with cancer, careful consideration should be given to the risk of COVID-19 in leukemia. Instead of reducing patient access to specialized cancer centers and modifying therapies to ones with unproven curative benefit, there is more rationale for less intensive, yet effective therapies that may require fewer clinic visits or hospitalizations. Here, we offer recommendations on the optimization of leukemia management during high-risk COVID-19 periods.


title: Chemical contrast for imaging living systems: molecular vibrations drive CARS microscopy

text: Cellular biomolecules contain unique molecular vibrations that can be visualized by coherent anti-Stokes Raman scattering (CARS) microscopy without the need for labels. Here we review the application of CARS microscopy for label-free imaging of cells and tissues using the natural vibrational contrast that arises from biomolecules like lipids as well as for imaging of exogenously added probes or drugs. High-resolution CARS microscopy combined with multimodal imaging has allowed for dynamic monitoring of cellular processes such as lipid metabolism and storage, the movement of organelles, adipogenesis and host-pathogen interactions and can also be used to track molecules within cells and tissues. The CARS imaging modality provides a unique tool for biological chemists to elucidate the state of a cellular environment without perturbing it and to perceive the functional effects of added molecules.


title: Changes in temperature alter the potential outcomes of virus host shifts

text: Host shifts–where a pathogen jumps between different host species–are an important source of emerging infectious disease. With on-going climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, while the mean viral load did not. This suggests that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures, and proxies for thermal optima (critical thermal maximum and minimum or basal metabolic rate). These results suggest that whilst the rank order of species susceptibilities may remain the same with changes in temperature, some species may become more susceptible to a novel pathogen, and others less so.


title: A COVID-19 Risk Assessment Decision Support System for General Practitioners: Design and Development Study

text: BACKGROUND: The coronavirus disease (COVID-19) has become an urgent and serious global public health crisis. Community engagement is the first line of defense in the fight against infectious diseases, and general practitioners (GPs) play an important role in it. GPs are facing unique challenges from disasters and pandemics in delivering health care. However, there is still no suitable mobile management system that can help GPs collect data, dynamically assess risks, and effectively triage or follow-up with patients with COVID-19. OBJECTIVE: The aim of this study is to design, develop, and deploy a mobile-based decision support system for COVID-19 (DDC19) to assist GPs in collecting data, assessing risk, triaging, managing, and following up with patients during the COVID-19 outbreak. METHODS: Based on the actual scenarios and the process of patients using health care, we analyzed the key issues that need to be solved and designed the main business flowchart of DDC19. We then constructed a COVID-19 dynamic risk stratification model with high recall and clinical interpretability, which was based on a multiclass logistic regression algorithm. Finally, through a 10-fold cross-validation to quantitatively evaluate the risk stratification ability of the model, a total of 2243 clinical data consisting of 36 dimension clinical features from fever clinics were used for training and evaluation of the model. RESULTS: DDC19 is composed of three parts: mobile terminal apps for the patient-end and GP-end, and the database system. All mobile terminal devices were wirelessly connected to the back end data center to implement request sending and data transmission. We used low risk, moderate risk, and high risk as labels, and adopted a 10-fold cross-validation method to evaluate and test the COVID-19 dynamic risk stratification model in different scenarios (different dimensions of personal clinical data accessible at an earlier stage). The data set dimensions were (2243, 15) when only using the data of patients’ demographic information, clinical symptoms, and contact history; (2243, 35) when the results of blood tests were added; and (2243, 36) after obtaining the computed tomography imaging results of the patient. The average value of the three classification results of the macro–area under the curve were all above 0.71 in each scenario. CONCLUSIONS: DCC19 is a mobile decision support system designed and developed to assist GPs in providing dynamic risk assessments for patients with suspected COVID-19 during the outbreak, and the model had a good ability to predict risk levels in any scenario it covered.


title: Effect of income on the cumulative incidence of COVID-19: an ecological study

text: OBJECTIVE: to analyze the relationship between per capita income and the cumulative incidence of COVID-19 in the neighborhoods of the city of Rio de Janeiro, RJ, Brazil. METHOD: an ecological study using neighborhoods as units of analysis. The cumulative incidence rate per 100,000 inhabitants and the median of potential confounding variables (sex, race, and age) were calculated. Multiple analysis included quantile regression, estimating the regression coefficients of the variable income for every five percentiles from the 10(th) to 90(th) percentiles to verify the relationship between income and incidence. RESULTS: the city’s rate was 36.58 new cases per 100,000 inhabitants. In general, the highest rates were observed in the wealthiest regions. Multiple analysis was consistent with this observation since the per capita income affected all percentiles analyzed, with a median regression coefficient of 0.02 (p-value <0.001; R(2) 32.93). That is, there is an increase of R$ 0.02 in the neighborhood’s per capita income for every unit of incidence. CONCLUSION: cumulative incident rates of COVID-19 are influenced by one’s neighborhood of residency, suggesting that access to testing is uneven.


title: Are Vapers More Susceptible to COVID-19 Infection?

text: Background COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Electronic cigarette use (vaping) rapidly gained popularity in the US in recent years. Whether electronic cigarette users (vapers) are more susceptible to COVID-19 infection is unknown. Methods Using integrated data in each US state from the 2018 Behavioral Risk Factor Surveillance System (BRFSS), United States Census Bureau and the 1Point3Acres.com website, generalized estimating equation (GEE) models with negative binomial distribution assumption and log link functions were used to examine the association of weighted proportions of vapers with number of COVID-19 infections and deaths in the US. Results The weighted proportion of vapers who used e-cigarettes every day or some days ranged from 2.86% to 6.42% for US states. Statistically significant associations were observed between the weighted proportion of vapers and number of COVID-19 infected cases as well as COVID-19 deaths in the US after adjusting for the weighted proportion of smokers and other significant covariates in the GEE models. With every one percent increase in weighted proportion of vapers in each state, the number of COVID-19 infected cases increase by 0.3139 (95% CI: 0.0554 - 0.5723) and the number of COVID-19 deaths increase by 0.3705 (95% CI: 0.0623 - 0.6786) in log scale in each US state. Conclusions The positive associations between the proportion of vapers and the number of COVID-19 infected cases and deaths in each US state suggest an increased susceptibility of vapers to COVID-19 infections and deaths.


title: Wild boars harboring porcine epidemic diarrhea virus (PEDV) may play an important role as a PEDV reservoir

text: Abstract Porcine epidemic diarrhea virus (PEDV) is a burdensome pathogen in the swine industry. Wild boar population poses a high risk for reservoir of viral pathogen. Two hundred eighty seven samples from wild boar (Sus scrofa) collected in South Korea during 2010/11 were analyzed using RT-PCR, revealing a PEDV infection rate of 9.75% (28/287). PEDV positive samples were distributed throughout the mainland of South Korea, clustering at the northern border adjacent to the Demilitarized Zone (DMZ) and in mountainous regions. PEDV in wild boar was genetically similar to Chinese PEDV strains in phylogenetic investigations. Our results indicated that PEDV is circulating in the wild boar and provided a novel knowledge into epidemiology of PEDV infection.


title: Establishment of a new bovine leukosis virus producing cell line

text: Abstract Due to the prevalence of different bovine leukosis virus (BLV) species in the cattle population in Europe, problems may arise in the serological diagnosis of BLV infections. In addition, earlier investigations demonstrated that contamination of the BLV antigen-producing cell culture systems by bovine viral diarrhea virus (BVDV) may give rise to misinterpretation of serological test results after BVDV vaccination of cattle. By co-cultivation of peripheral leukocytes of a BLV-infected cow with a permanent sheep kidney cell line, a new BLV-producing cell line named PO714 was established. This line carries a BLV provirus of the Belgian species and has been tested to be free of a variety of possibly contaminating viruses and mycoplasms. Investigations of a panel of well-characterised sera by agar gel immunodiffusion (AGID) and capture ELISA (cELISA) tests using antigen prepared from this new cell line in comparison with antigen of the well-known cell line FLK/BLV yielded comparable results. False positive results caused by BVDV cross-reactions could be eliminated when tests were carried out with antigen derived from the new cell line.


title: Le virome humain

text: Résumé Le virome humain est une représentation exhaustive des virus capables d’infecter l’homme. Cette dénomination regroupe bien sûr les virus eucaryotes responsables d’infections aiguës, d’infections chroniques et d’infections latentes, qu’elles soient symptomatiques ou non, mais également les virus procaryotes en raison de leurs rôles sur les communautés bactériennes hébergées dans les flores humaines. Certains auteurs incluent également les séquences virales endogènes conservées dans le génome humain au cours de l’évolution. Les techniques récentes de séquençage profond à haut débit ont permis de mieux caractériser le virome humain. Ces approches ont permis la description de nombreux nouveaux virus et également confirmé que les différents tissus humains arborent de manière asymptomatique une diversité virale importante qui peut être assimilée à une « flore virale ». Cette nouvelle vision des virus nécessite de reconsidérer le rôle biologique des virus dans l’organisme. Summary The human virome is the collection of viruses found in human, including viruses that infect eucaryotic cells, bacteriophages and virus-derived genetic elements in host chromosomes that can influence host-genes expression. Most of the recent knowledges regarding the human virome were driven by advances in high-throughput, deep sequencing approaches. Thanks to these new technologies, many new human viruses were described with, furthermore, the evidence of the presence of a resident viral community in most human tissus. This new concept will have profound implications for understanding the biological role of viruses in the human body.


title: The pathogenesis of multifocal osteonecrosis

text: Our objective was to study the incidence, etiology, and diagnosis of multifocal osteonecrosis (MFON) and its treatment options to facilitate an earlier diagnosis and to optimize treatment. A radiological investigation was performed in osteonecrosis patients with a high risk of MFON for a more accurate diagnosis between January 2010 and June 2015. For patients with osteonecrosis of both the hip and knee joints or for patients with a history of corticosteroid use or alcohol abuse who had osteonecrosis of one or more joints in the shoulder, ankle, wrist or elbow, magnetic resonance imaging (MRI) was also performed on other joints, regardless of whether these joints were symptomatic. Furthermore, we performed a radiological screening of 102 patients who had a negative diagnosis of MFON but were at a high risk; among them, another 31 MFON cases were successfully identified (30.4%). Thus, the incidence of MFON during the study period increased from 3.1% to 5.2%. Patients diagnosed with osteonecrosis and who are at a high risk of MFON should have their other joints radiologically examined when necessary. This will reduce missed diagnosis of MFON and facilitate an earlier diagnosis and treatment to achieve an optimal outcome.


title: Zur derzeitigen Bedeutung der Infektionskrankheiten

text: Einleitung Während der letzten beiden Jahrhunderte sind Hunderte von Infektionserregern entdeckt worden. Die epidemiologische Situation hinsichtlich der wichtigsten Infektionskrankheiten in Deutschland hat sich in den letzten zehn Jahren entscheidend geändert. Einem signifikanten Abfall der Hepatitis A- und B-Inzidenz steht die moderate Reduktion bei der Hepatitis C und der Tuberkulose gegenüber, während Masern und Hepatitis E erheblich an Bedeutung gewonnen haben. In dieser Arbeit werden Public Health-Maßnahmen zur Kontrolle von Infektionskrankheiten vor dem Hintergrund der Empfehlungen der Ständigen Impfkommission am Robert Koch-Institut diskutiert. Abstract During the last two centuries hundreds of infectious agents have been discovered. The epidemiological situation of the most important infectious diseases in Germany has changed significantly during the last ten years. A sharp decrease has been observed concerning Hepatitis A- and B-incidence and a moderate one in Hepatitis C and tuberculosis frequency, whereas measles and Hepatitis E-incidence showed a dramatic increase. In this article public health measures – e.g. chemoprophylaxis and vaccinations – for the control of infectious diseases are discussed using the recommendations of the permanent commission on vaccinations at the German Robert Koch Institute.


title: Studies on membrane topology, N-glycosylation and functionality of SARS-CoV membrane protein

text: The glycosylated membrane protein M of the severe acute respiratory syndrome associated coronavirus (SARS-CoV) is the main structural component of the virion and mediates assembly and budding of viral particles. The membrane topology of SARS-CoV M and the functional significance of its N-glycosylation are not completely understood as is its interaction with the surface glycoprotein S. Using biochemical and immunofluorescence analyses we found that M consists of a short glycosylated N-terminal ectodomain, three transmembrane segments and a long, immunogenic C-terminal endodomain. Although the N-glycosylation site of M seems to be highly conserved between group 1 and 3 coronaviruses, studies using a recombinant SARS-CoV expressing a glycosylation-deficient M revealed that N-glycosylation of M neither influence the shape of the virions nor their infectivity in cell culture. Further functional analysis of truncated M proteins showed that the N-terminal 134 amino acids comprising the three transmembrane domains are sufficient to mediate accumulation of M in the Golgi complex and to enforce recruitment of the viral spike protein S to the sites of virus assembly and budding in the ERGIC.


title: Chronic Allograft Dysfunction

text: Chronic, progressive, and irreversible loss of lung function is the major medium-term and long-term complication after lung transplantation and the leading cause of death. Over the past decade, progress has been made in understanding the pathogenesis of bronchiolitis obliterans. Alloimmune factors and nonalloimmune factors may contribute to its development. Understanding the precise mechanism of each type of chronic allograft dysfunction may open up the field for new preventive and therapeutic interventions. This article reviews major new insights into the clinical aspects, pathophysiology, risk factors, diagnosis, and management of chronic allograft dysfunction after lung transplantation.


title: Travel Health Implications for Women Traveling Abroad

text: Abstract International travel is increasing each year, and many travelers are female. Travel-related health risks include diseases, accidents, and other safety concerns. Whether traveling for business or pleasure, women should practice appropriate measures that minimize the impact travel can have on their health and well-being. Female travelers can have unique health risks related to pregnancy, lactation, and infectious disease. A large part of pretravel health preparation is often performed by nurses and should include a comprehensive health risk assessment, education, and vaccinations, all of which can help mitigate potential health risks for travelers.


title: MMP9 deficiency does not decrease blood brain barrier disruption, but increases astrocyte MMP3 expression during viral encephalomyelitis

text: Expression of matrix metalloproteinases (MMPs), especially MMP9 correlates with blood brain barrier (BBB) disruption during many neuroinflammatory diseases. During neurotropic coronavirus virus (JHMV) induced encephalomyelitis, MMP9 activity is restricted to neutrophils. Furthermore, myeloid cell depletion implicated MMP9 in facilitating leukocyte central nervous system (CNS) infiltration via loss of BBB integrity. The requirement of MMP9 in BBB disruption was thus assessed in JHMV infected MMP9 deficient (MMP9(−/−)) mice. Depletion of neutrophils reduced CNS accumulation of monocytes and T cells, albeit without affecting overall pathogenesis. By contrast, infected MMP9(−/−) mice revealed no differences in CNS leukocyte infiltration, composition or localization, consistent with BBB disruption similar to wild type (WT) mice. Unimpaired T cell mediated virus control supported an unexpectedly redundant role of MMP9 in promoting leukocyte access to the brain parenchyma. While MMP9 deficiency did not expand the overall limited pattern of MMP expression during JHMV infection, it coincided with MMP3 upregulation. MMP3 expression remained largely confined to astrocytes, similar to WT mice. These data demonstrate that neutrophil-derived MMP9 is not the sole mediator facilitating parenchymal leukocyte entry via BBB disruption during viral encephalomyelitis. Moreover, significantly enhanced MMP3 expression by astrocytes in infected MMP9(−/−) mice suggests an active role of resident cells in participating and potentially collaborating with infiltrating cells in regulating BBB permeability. Overall, these results highlight the complexity of targeting individual MMPs as a strategy to regulate inflammation.


title: Disposable DNA Amplification Chips with Integrated Low-Cost Heaters †

text: Fast point-of-use detection of, for example, early-stage zoonoses, e.g., Q-fever, bovine tuberculosis, or the Covid-19 coronavirus, is beneficial for both humans and animal husbandry as it can save lives and livestock. The latter prevents farmers from going bankrupt after a zoonoses outbreak. This paper describes the development of a fabrication process and the proof-of-principle of a disposable DNA amplification chip with an integrated heater. Based on the analysis of the milling process, metal adhesion studies, and COMSOL MultiPhysics heat transfer simulations, the first batch of chips has been fabricated and successful multiple displacement amplification reactions are performed inside these chips. This research is the first step towards the development of an early-stage zoonoses detection device. Tests with real zoonoses and DNA specific amplification reactions still need to be done.


title: Extraction, characterization and bioactivities of novel purified polysaccharides from Baphicacanthis Cusiae Rhizoma et Radix

text: The purpose of this study was to investigate the extraction, characterization and bioactivities of purified water-soluble polysaccharides (BCP) from Baphicacanthis Cusiae Rhizoma et Radix. Based on the response surface methodology, the optimal extraction parameters were obtained as follows: extraction temperature of 60.0 °C, extraction time of 35.0 min, and ratio of water to raw material of 24.5 ml/g. Then, BCP was separated and purified by chromatography of DEAE-52 and Sephadex G-100, and obtained two purified fractions, named as BCP-1 and BCP-2. Their molecular weights were respectively 11.6 and 26.7 KDa with mainly composed of glucose, arabinose and galactose. BCP-2 had higher contents of sulfuric radical and uronic acid than BCP-1. Finally, their antioxidant and anti-inflammatory activities were evaluated. Both of BCP-1 and BCP-2 exhibited strong antioxidant activity in vitro, and the antioxidant of BCP-2 was better. Besides, they showed ideal anti-inflammatory activity in vitro and in vivo.