title: Interventional oncology at the time of COVID-19 pandemic: problems and solutions

text: Abstract The COVID-19 pandemic has deeply impacted the activity of interventional oncology in hospitals and cancer centers. In this review based on official recommendations of different international societies, but also on local solutions found in different expert large-volume centers, we discuss the changes that need to be done for the organization, safety, and patient management in interventional oncology. A literature review of potential solutions in a context of scarce anesthesiologic resources, limited staff and limited access to hospital beds are proposed and discussed based on the literature data.


title: An international multicentre study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise

text: BACKGROUND: The outbreak of Covid-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern. There is an urgent need for ethical frameworks to balance the need for liver transplantation against the availability of national resources. METHODS: We performed an international multi-center study of transplant centers to understand the evolution of policies for transplant prioritization in response to the pandemic in March 2020. To describe the ethical tension arising in this setting, we propose a novel ethical framework, the Quadripartite Equipoise (QE) score, that is applicable to liver transplantation in the context of limited national resources. RESULTS: Seventeen large- and medium- sized liver transplant centers from twelve countries across four continents participated. Ten centers opted to limit transplant activity in response to the pandemic, favoring a “sickest-first” approach. Conversely, some larger centers opted to continue routine transplant activity in order to balance waiting list mortality. To model these and other ethical tensions, we computed a QE score using 4 factors - Recipient Outcome, Donor/Graft Safety, Waiting List Mortality and Healthcare Resources for seven countries. The fluctuation of the QE score over time accurately reflects the dynamic changes in the ethical tensions surrounding transplant activity in a pandemic. CONCLUSIONS: This four-dimensional model of Quadripartite Equipoise addresses the ethical tensions in the current pandemic. It serves as a universally applicable framework to guide regulation of transplant activity in response to the increasing burden on healthcare systems to allow greater global solidarity and transparency in these austere times.


title: Pathogenicity of neutralization escape mutants of mouse hepatitis virus : correlation with T- and B-cell depletions

text: Summary Viral pathogenicity is a result of an imbalance between viral replication and the host's immune defences. When the virus is lymphotropic, understanding the pathogenic process of the viral disease becomes complicated because virus/lymphocyte interactions can alter the cell's integrity and subsequently induce immunodeficiency. The immune system plays an important role in the outcome of acute disease induced by the mouse hepatitis virus type 3 (MHV3). The use of attenuated escape mutants provides a tool to study the role of viral properties involved in its pathogenicity. We selected MHV3 mutants by virtue of their resistance to neutralization by monoclonal antibodies (mAb), in order to study their pathogenic properties. We reported that two MHV3 escape mutants were attenuated in their pathogenic properties according to inoculation site and with regard to survival time and ability to deplete T- and B-cell subpopulations in the spleen, thymus and bone marrow of susceptible Balb/c mice. The highly attenuated CL12 mutant could not induce depletion in T or B cells following intraperitoneal (i.p.) or intranasal (i.n.) inoculations, at three days postinfection. The less attenuated 51.6 mutant, however, maintained the ability to deplete T and B cells following i.p. inoculation, as described with the pathogenic MHV3. In contrast, no depletion of T cells following i.n. inoculation was induced with this mutant, although B lineage cells decreased. The use of such mutants enabled us to examine the role of each compartment of the immune system, since the highly attenuated CL12 mutant induced no immunodeficiency, as defined by immune cell depletion, whereas the less attenuated 51.6 mutant maintained its ability to decrease only the B-cell compartment after i.n. inoculation. Results are discussed with regard to the virus/lymphocyte interactions during the pathogenic process.


title: A positive perspective during COVID-19 related to groundwater crisis

text: The months from March to June refer as water crisis months in many places of India, because in these months of summer generally, Indian people face shortage of water. In the summer season, groundwater level decreases due to high temperature and increased evaporation of water in most of the places. This present discussion is focused on one positive aspect during the COVID-19 pandemic, which is related to rainfall during this summer in India. It has been observed that the rainfall in India in the months of March to May (as of now, on May 18, 2020) is high as compared to previous years and it might increase the groundwater level and people of India would not face a water crisis during this summer.


title: Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis

text: Abstract When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1–2.4 × 106-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains' and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.


title: Exploring the coronavirus epidemic using the new WashU Virus Genome Browser

text: Since its debut in mid-December, 2019, the novel coronavirus (2019-nCoV) has rapidly spread from its origin in Wuhan, China, to several countries across the globe, leading to a global health crisis. As of February 7, 2020, 44 strains of the virus have been sequenced and uploaded to NCBI’s GenBank [1], providing insight into the virus’s evolutionary history and pathogenesis. Here, we present the WashU Virus Genome Browser, a web-based portal for viewing virus genomic data. The browser is home to 16 complete 2019-nCoV genome sequences, together with hundreds of related viral sequences including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus. In addition, the browser features unique customizability, supporting user-provided upload of novel viral sequences in various formats. Sequences can be viewed in both a track-based representation as well as a phylogenetic tree-based view, allowing the user to easily compare sequence features across multiple strains. The WashU Virus Genome Browser inherited many features and track types from the WashU Epigenome Browser, and additionally incorporated a new type of SNV track to address the specific needs of viral research. Our Virus Browser portal can be accessed at https://virusgateway.wustl.edu, and documentation is available at https://virusgateway.readthedocs.io/.


title: Disaster Nursing: A Retrospective Review

text: This article presents a review of the literature related to disaster preparedness and nursing. A definition of disaster as set forth by the American Red Cross is provided. Eight themes, including (1) defining disaster, (2) nursing during and after disaster, (3) nursing education in disaster preparedness, (4) military nurse preparedness, (5) postdisaster stress, (6) ethical issues and intent to respond, (7) policy, and (8) hospital emergency policy, were derived from the review and are explored in this article. Although a plethora of disaster-related literature exists, the voice of the nurses who worked during these disasters is missing. Areas of proposed research illuminated by current research are suggested.


title: Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States

text: Abstract In the United States, there is currently an exponential growth for the COVID-19 cases. The US president’s coronavirus guidelines for Americans “30 Days to Slow The Spread” are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines.


title: H7N9 influenza and its impact on pregnancy

text: Abstract This short article specifically focuses on the new emerging H7N9 influenza which has just been observed since early 2013. As a new disease, it is lack for the knowledge on the new H7N9 influenza. Here, the author will discuss on the impact of emerging H7N9 influenza on pregnancy.


title: World Competitive Contests (WCC) algorithm: A novel intelligent optimization algorithm for biological and non-biological problems

text: Abstract Since different sciences face lots of problems which cannot be solved in reasonable time order, we need new methods and algorithms for getting acceptable answers in proper time order. In the present study, a novel intelligent optimization algorithm, known as WCC (World Competitive Contests), has been proposed and applied to find the transcriptional factor binding sites (TFBS) and eight benchmark functions discovery processes. We recognize the need to introduce an intelligent optimization algorithm because the TFBS discovery is a biological and an NP-Hard problem. Although there are some intelligent algorithms for the purpose of solving the above-mentioned problems, an optimization algorithm with good and acceptable performance, which is based on the real parameters, is essential. Like the other optimization algorithms, the proposed algorithm starts with the first population of teams. After teams are put into different groups, they will begin competing against their rival teams. The highly qualified teams will ascend to the elimination stage and will play each other in the next rounds. The other teams will wait for a new season to start. In this paper, we’re going to implement our proposed algorithm and compare it with five famous optimization algorithms from the perspective of the following: the obtained results, stability, convergence, standard deviation and elapsed time, which are applied to the real and randomly created datasets with different motif sizes. According to our obtained results, in many cases, the WCC׳s performance is better than the other algorithms’.


title: Surface glycoprotein of Borna disease virus mediates virus spread from cell to cell

text: Borna disease virus (BDV) is a non‐segmented negative‐stranded RNA virus that maintains a strictly neurotropic and persistent infection in affected end hosts. The primary target cells for BDV infection are brain cells, e.g. neurons and astrocytes. The exact mechanism of how infection is propagated between these cells and especially the role of the viral glycoprotein (GP) for cell–cell transmission, however, are still incompletely understood. Here, we use different cell culture systems, including rat primary astrocytes and mixed cultures of rat brain cells, to show that BDV primarily spreads through cell–cell contacts. We employ a highly stable and efficient peptidomimetic inhibitor to inhibit the furin‐mediated processing of GP and demonstrate that cleaved and fusion‐active GP is strictly necessary for the cell‐to‐cell spread of BDV. Together, our quantitative observations clarify the role of Borna disease virus‐glycoprotein for viral dissemination and highlight the regulation of GP expression as a potential mechanism to limit viral spread and maintain persistence. These findings furthermore indicate that targeting host cell proteases might be a promising approach to inhibit viral GP activation and spread of infection.


ENDOSCOPIC FINDINGS IN PATIENTS INFECTED WITH 2019 NOVEL CORONAVIRUS IN LOMBARDY, ITALY


title: An insect cell derived respiratory syncytial virus (RSV) F nanoparticle vaccine induces antigenic site II antibodies and protects against RSV challenge in cotton rats by active and passive immunization

text: Abstract Post-infectious immunity to respiratory syncytial virus (RSV) infection results in limited protection as evidenced by the high rate of infant hospitalization in the face of high titer, maternally derived RSV-specific antibodies. By contrast, RSV fusion (F) glycoprotein antigenic site II humanized monoclonal antibodies, palivizumab and motavizumab, have been shown to reduce RSV-related hospitalization in infants. Immunogenicity and efficacy studies were conducted in cotton rats comparing a recombinant RSV F nanoparticle vaccine with palivizumab and controlled with live RSV virus intranasal immunization and, formalin inactivated RSV vaccine. Active immunization with RSV F nanoparticle vaccine containing an alum adjuvant induced serum levels of palivizumab competing antibody (PCA) greater than passive administration of 15mg/kg palivizumab (human prophylactic dose) in cotton rats and neutralized RSV-A and RSV-B viruses. Immunization prevented detectable RSV replication in the lungs and, unlike passive administration of palivizumab, in the nasal passage of challenged cotton rats. Histology of lung tissues following RSV challenge showed no enhanced disease in the vaccinated groups in contrast to formalin inactivated ‘Lot 100’ vaccine. Passive intramuscular administration of RSV F vaccine-induced immune sera one day prior to challenge of cotton rats reduced viral titers by 2 or more log10 virus per gram of lung and nasal tissue and at doses less than palivizumab. A recombinant RSV F nanoparticle vaccine protected lower and upper respiratory tract against both RSV A and B strain infection and induced polyclonal palivizumab competing antibodies similar to but potentially more broadly protective against RSV than palivizumab.


Pancreatitis aguda en paciente con infección por COVID-19


title: Infection Density and Epidemic Size of COVID-19 in China outside the Hubei province

text: The novel coronavirus (COVID-19) has spread to almost all countries in the world, claiming more than 160,000 lives and sickening more than 2,400,000 people by April 21, 2020. There has been research showing that on average, each infected person spreads the infection to more than two persons. Therefore the majority of the population is at risk of infection if no intervention measures were undertaken. The true size of the COVID-19 epidemic remains unknown, as a significant proportion of infected individuals only exhibit mild symptoms or are even asymptomatic. A timely assessment of the evolving epidemic size is crucial for resource allocation and triage decisions. In this article, we modify the back-calculation algorithm to obtain a lower bound estimate of the number of COVID-19 infected persons in China outside the Hubei province. We estimate the infection density among infected and show that the drastic control measures enforced throughout China following the lockdown of Wuhan City effectively slowed down the spread of the disease in two weeks. Our findings from China are expected to provide guidelines and enlightenment for surveillance and control activities of COVID-19 in other countries around the world.


title: Preparation of polyoxometalate-doped aminosilane-modified silicate hybrid as a new barrier of chem-bio toxicant

text: Nanohybrid membranes based on the Keggin-type polyoxometalate (POM) H(5)PV(2)Mo(10)O(40) and aminosilane-modified silicate (Ormosil and Ormosil(NR(4)(+)Cl(−))) hybrids were synthesized as a new barrier to protect against simulants of chemical and biological toxicant. The (31)P NMR and XPS results indicated that POM was bound to the Ormosil and Ormosil(NR(4)(+)Cl(−)) hybrids after impregnation. The antibacterial effects of the hybrids and hybrid-impregnated fabrics against Gram-negative and Gram-positive bacteria were investigated with zone of inhibition, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and plate-counting method. The MIC/MBC values of Ormosil(NR(4)(+)Cl(−))/POM and Ormosil/POM against bacteria were 0.267/2.67 and 2.67/26.7, respectively, and the percentage reduction of bacteria was approximately 100% after 20 laundry cycles of their fabrics. The reaction products and mechanisms of the adsorptive degradation of 2-chloroethylethylsulfide (CEES) by hybrids were investigated with (13)C NMR. The results of this study showed that POM-doped Ormosil systems are capable of destroying bacteria and CEES.


title: Phylogenetic characterization of enterovirus 68 strains in patients with respiratory syndromes in Italy

text: Enterovirus 68 (EV‐D68) was associated with mild to severe respiratory infections. In the last 4 years, circulation of different EV‐D68 strains has been documented worldwide. In this study, the phylogenetic characterization of nine EV‐D68 strains identified in patients in the 2010–2012 period and 12 additional EV‐D68 Italian strains previously identified in 2008 in Italy was described. From January 2010 to December 2012, a total of 889 respiratory specimens from 588 patients stayed or visited at the Fondazione IRCCS Policlinico San Matteo were positive for HRV or HEV. Extracted nucleic acids were amplified by one‐step RT‐PCR with primer specific for VP1 region of EV‐D68 and purified positive PCR products were directly sequenced. Overall, 9/3736 (0.24%) patients were EV‐D68 positive. Of these, 7/9 (77.8%) were pediatric and two (22.2%) were adults. Five out of seven (71.4%) pediatric patients had lower respiratory tract infection with oxygen saturation <94%. Four cases were detected from August through October 2010, while five other cases from September through December 2012. The Italian EV‐D68 strains in 2008 belonged to clade A (n = 5) and clade C (n = 7). In 2010 all the Italian strains belonged to clade A (n = 4) and in 2012, four Italian strains belonged to clade B and one to clade A. In conclusion, we provide additional evidence supporting a role of EV‐D68 in severe respiratory infection in pediatric patients. In addition, all the three EV‐D68 clades circulating worldwide were identified in Italy in a 5‐year period of time. J. Med. Virol. 86:1590–1593, 2014. © 2013 Wiley Periodicals, Inc.


title: Organization of cholinergic, catecholaminergic, serotonergic and orexinergic nuclei in three strepsirrhine primates: Galago demidoff, Perodicticus potto and Lemur catta

text: Abstract The nuclear organization of the cholinergic, catecholaminergic, serotonergic and orexinergic systems in the brains of three species of strepsirrhine primates is presented. We aimed to investigate the nuclear complement of these neural systems in comparison to those of simian primates, megachiropterans and other mammalian species. The brains were coronally sectioned and immunohistochemically stained with antibodies against choline acetyltransferase, tyrosine hydroxylase, serotonin and orexin-A. The nuclei identified were identical among the strepsirrhine species investigated and identical to previous reports in simian primates. Moreover, a general similarity to other mammals was found, but specific differences in the nuclear complement highlighted potential phylogenetic interrelationships. The central feature of interest was the structure of the locus coeruleus complex in the primates, where a central compactly packed core (A6c) of tyrosine hydroxylase immunopositive neurons was surrounded by a shell of less densely packed (A6d) tyrosine hydroxylase immunopositive neurons. This combination of compact and diffuse divisions of the locus coeruleus complex is only found in primates and megachiropterans of all the mammalian species studied to date. This neural character, along with variances in a range of other neural characters, supports the phylogenetic grouping of primates with megachiropterans as a sister group.


title: How an Epidemic Outbreak Impacts Happiness: Factors that Worsen (vs. Protect) Emotional Well-being during the Coronavirus Pandemic

text: What are the factors that worsen (vs. protect) emotional well-being during a pandemic outbreak such as COVID-19? Through two large-scale nationwide surveys (N(1) = 11,131; N(2) = 3,000) conducted in China immediately before versus during the coronavirus outbreak, we found that the onset of the coronavirus epidemic led to a 74% drop in overall emotional well-being. Factors associated with the likelihood of contracting the disease (e.g., residing near the epicenter), extent of potential harm (e.g., being an elderly), and relational issues (e.g., those within a marriage) exacerbated the detrimental effect of the outbreak on emotional well-being. Further, individuals’ perception of their knowledge about coronavirus infection was another factor. Regardless of the actual amount of knowledge they possessed, those perceiving themselves as more knowledgeable, were able to experience more happiness during the outbreak. Higher perceived knowledge was associated with a stronger sense of control, which mediated the differences in emotional well-being. These patterns persisted even after controlling for a host of demographic and economic variables. In conclusion, public policies and mental health interventions aimed at boosting/protecting psychological well-being during epidemics should take account of these factors.


title: Prevent and predict

text: As the COVID-19 outbreak continues, the next pandemic could be prevented by ending the wildlife trade and reinvesting in the monitoring of potential zoonoses.


title: Limitations of using feline coronavirus spike protein gene mutations to diagnose feline infectious peritonitis

text: Feline infectious peritonitis (FIP) is a fatal disease of cats, and a sequela of systemic feline coronavirus (FCoV) infection. Mutations in the viral spike (S) gene have been associated with FCoVs found in tissues from cats with FIP, but not FCoVs found in faeces from healthy cats, and are implicated in monocyte/macrophage tropism and systemic spread. This study was designed to determine whether S gene mutation analysis can reliably diagnose FIP. Cats were categorised as with FIP (n = 57) or without FIP (n = 45) based on gross post-mortem and histopathological examination including immunohistochemistry for FCoV antigen. RNA was purified from available tissue, fluid and faeces. Reverse-transcriptase quantitative-PCR (RT-qPCR) was performed on all samples using FCoV-specific primers, followed by sequencing of a section of the S gene on RT-qPCR positive samples. Samples were available from a total of 102 cats. Tissue, fluid, and faecal samples from cats with FIP were more likely to be FCoV RT-qPCR-positive (90.4, 78.4 and 64.6% respectively) than those from cats without FIP (7.8, 2.1 and 20% respectively). Identification of S gene mutated FCoVs as an additional step to the detection of FCoV alone, only moderately increased specificity for tissue samples (from 92.6 to 94.6%) but specificity was unchanged for fluid samples (97.9%) for FIP diagnosis; however, sensitivity was markedly decreased for tissue (from 89.8 to 80.9%) and fluid samples (from 78.4 to 60%) for FIP diagnosis. These findings demonstrate that S gene mutation analysis in FCoVs does not substantially improve the ability to diagnose FIP as compared to detection of FCoV alone. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0467-9) contains supplementary material, which is available to authorized users.


title: COVID-19 pandemic – A focused review for clinicians

text: Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics and society. A wealth of data has been generated since its emergence in December 2019 and it is vital for clinicians to keep up with this data from across the world at a time of uncertainty and constantly evolving guidelines and clinical practice. Objectives Here we provide an update for clinicians on the recent developments about virology, diagnostics, clinical presentation, viral shedding, and treatment options for COVID-19 based on current literature. Sources We considered published peer-reviewed papers and non-peer-reviewed pre-print manuscripts on COVID19 and related aspects with an emphasis on clinical management aspects. Content We describe the virological characteristics of SARS-CoV-2 and clinical course of COVID-19 with an emphasis on diagnostic challenges, duration of viral shedding, severity markers and current treatment options. Implications The key challenge in managing COVID-19 remains the patient density. However, accurate diagnoses as well as early identification and management of high-risk severe cases are important for many clinicians. For improved management of cases, there is a need to understand test probability of serology, qRT-PCR and radiological testing, and the efficacy of available treatment options that could be used in severe cases with a high risk of mortality.


COVID‐19 in Turkey: An urgent need for the implementation of preparedness and response strategies


title: Paramyxovirus membrane fusion: Lessons from the F and HN atomic structures

text: Abstract Paramyxoviruses enter cells by fusion of their lipid envelope with the target cell plasma membrane. Fusion of the viral membrane with the plasma membrane allows entry of the viral genome into the cytoplasm. For paramyxoviruses, membrane fusion occurs at neutral pH, but the trigger mechanism that controls the viral entry machinery such that it occurs at the right time and in the right place remains to be elucidated. Two viral glycoproteins are key to the infection process—an attachment protein that varies among different paramyxoviruses and the fusion (F) protein, which is found in all paramyxoviruses. For many of the paramyxoviruses (parainfluenza viruses 1–5, mumps virus, Newcastle disease virus and others), the attachment protein is the hemagglutinin/neuraminidase (HN) protein. In the last 5 years, atomic structures of paramyxovirus F and HN proteins have been reported. The knowledge gained from these structures towards understanding the mechanism of viral membrane fusion is described.


title: Extracorporeal shockwave therapy in osteonecrosis of femoral head: A systematic review of now available clinical evidences

text: BACKGROUND: Osteonecrosis is an incapacitating disorder with high morbidity. Though extracorporeal shockwave therapy (ESWT) provides a noninvasive treatment option, controversial subjects still exist about its effectiveness, indications, and mechanism of action. METHODS: An electronic databases search was performed using PubMed, Embase, and the Cochrane library to collect clinical trials, case reports, and cases series on this topic and then useful data were extracted and appraised by experienced clinicians. We evaluated the quality of included evidences by using the Oxford Centre for evidence-based medicine (EBM) Levels of Evidence. RESULTS: A total of 17 articles including 2 case reports, 9 open label trials, 2 cohorts, and 6 randomized controlled trials were considered to be eligible for this systematic review. Visual analog scale (VAS), Harris hip scores, and the imaging results were the frequently-used outcome estimates of included studies. CONCLUSION: By systematically analyzing these evidences, we could conclude that ESWT could act as a safe and effective method to improve the motor function and relieve the pain of patients with osteonecrosis of femoral hip, especially those at early stage. Imaging revealed that bone marrow edema was significantly relieved, but the necrotic bone could not be reversed after ESWT. This technique could slow or even block the progression of ONFH and therefore reduce the demand for surgery. Collaboration with other conservative modalities would not improve the curative benefits of ESWT. Meanwhile, ONFH with various risk factors showed similar reaction to this noninvasive treatment method. However, these conclusions should be interpreted carefully for the low-quality of included publications and further studies are requisite to validate the effect of ESWT in ONFH.


title: Crystal structure of the catalytic domain of Clostridium perfringens neuraminidase in complex with a non-carbohydrate-based inhibitor, 2-(cyclohexylamino)ethanesulfonic acid

text: Abstract Anti-bacterial and anti-viral neuraminidase agents inhibit neuraminidase activity catalyzing the hydrolysis of terminal N-acetylneuraminic acid (Neu5Ac) from glycoconjugates and help to prevent the host pathogenesis that lead to fatal infectious diseases including influenza, bacteremia, sepsis, and cholera. Emerging antibiotic and drug resistances to commonly used anti-neuraminidase agents such as oseltamivir (Tamiflu) and zanamivir (Relenza) have highlighted the need to develop new anti-neuraminidase drugs. We obtained a serendipitous complex crystal of the catalytic domain of Clostridium perfringens neuraminidase (CpNanICD) with 2-(cyclohexylamino)ethanesulfonic acid (CHES) as a buffer. Here, we report the crystal structure of CpNanICD in complex with CHES at 1.24 Å resolution. Amphipathic CHES binds to the catalytic site of CpNanICD similar to the substrate (Neu5Ac) binding site. The 2-aminoethanesulfonic acid moiety and cyclohexyl groups of CHES interact with the cluster of three arginine residues and with the hydrophobic pocket of the CpNanICD catalytic site. In addition, a structural comparison with other bacterial and human neuraminidases suggests that CHES could serve as a scaffold for the development of new anti-neuraminidase agents targeting CpNanI.


INTRODUCTION: The Infectious Disease Clinical Research Program’s (IDCRP) Emerging Infectious Diseases and Antimicrobial Resistance (EIDAR) Research Area is a Department of Defense (DoD) clinical research capability that is responsive and adaptive to emerging infectious disease (EID) threats to US military readiness. Among active-duty and other Military Health System (MHS) beneficiaries, EIDAR research is largely focused on evaluating the incidence, risk factors, and acute- and long-term health effects of military-relevant EIDs, especially those caused by high-consequence pathogens or are responsible for outbreaks among US military populations. The EIDAR efforts also address Force Health Protection concerns associated with antimicrobial resistance and antimicrobial stewardship practices within the MHS. METHODS: The EIDAR studies utilize the approach of: (1) Preparing for emergent conditions to systematically collect clinical specimens and data and conduct clinical trials to assist the military with a scientifically appropriate response; and (2) Evaluating burden of emergent military-relevant infectious diseases and assessing risks for exposure and development of post-infectious complications and overall impact on military readiness. RESULTS: In response to the Ebola virus epidemic in West Africa, the IDCRP partnered with the National Institutes of Health in developing a multicenter, randomized safety and efficacy study of investigational therapeutics in Ebola patients. Subsequently, the EIDAR team developed a protocol to serve as a contingency plan (EpICC-EID) to allow clinical research activities to occur during future outbreaks of viral hemorrhagic fever and severe acute respiratory infections among MHS patients. The EIDAR portfolio recently expanded to include studies to understand exposure risks and impact on military readiness for a diversity of EIDs, such as seroincidence of non-Lyme disease borreliosis and Coccidioides fungal infections among high-risk military populations. The team also launched a new prospective study in response to the recent Zika epidemic to conduct surveillance for Zika and other related viruses among MHS beneficiaries in Puerto Rico. Another new study will prospectively follow U.S. Marines via an online health assessment survey to assess long-term health effects following the largest DoD Shiga Toxin-Producing Escherichia coli outbreak at the U.S. Marine Corps Recruit Depot-San Diego. In cooperation with the Trauma-Related Infections Research Area, the EIDAR Research Area is also involved with the Multidrug-Resistant and Virulent Organisms Trauma Infections Initiative, which is a collaborative effort across DoD laboratories to characterize bacterial and fungal isolates infecting combat-related extremity wounds and link lab findings to clinical outcomes. Furthermore, the EIDAR team has developed an Antimicrobial Resistance and Stewardship Collaborative Clinical Research Consortium, comprised of Infectious Disease and Pharmacy specialists. CONCLUSIONS: The EIDAR Research Area is responsive to military-relevant infectious disease threats that are also frequently global public health concerns. Several new EIDAR efforts are underway that will provide Combatant Command Surgeons, Infectious Diseases Service Chiefs, and other Force Health Protection stakeholders with epidemiological information to mitigate the impact of EIDs and antimicrobial resistance on the health of U.S. military service members and their dependents.


title: Comparison of Perceived and Observed Hand Hygiene Compliance in Healthcare Workers in MERS-CoV Endemic Regions

text: This study investigated healthcare workers’ perceptions of hand hygiene practices by comparing personal reports, as assessed by questionnaires, to direct observations of the workers’ hand hygiene practices. The study employed a cross-sectional research design. Observations were made using a 16-item checklist, based on three sources: Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and Boyce and Pittet’s guidelines of hand hygiene. The checklist was used for both direct-observation and self-reported data collection purposes. Pearson correlation and Multivariate Analysis of Covariance (MANCOVA) were utilized to statistically determine the relationship between healthcare workers’ reports of hand hygiene practices and observed hand hygiene behaviors. The study was conducted in the outpatient examination rooms and emergency departments of three types of hospitals in the Eastern region of Saudi Arabia where Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic and is observed in routine cases and outbreaks. The total sample size included 87 physicians and nurses recruited while on duty during the scheduled observation periods, with each healthcare worker being observed during individual medical examinations with at least three patients. No statistically significant correlations between the healthcare workers’ perceptions of hand hygiene practices and healthcare workers’ actual behaviors were evident. Based on the self-report questionnaires, significant differences were found between physicians’ and nurses’ hand hygiene practices reports. Healthcare workers clearly understand the importance of careful hand hygiene practices, but based on researchers’ observations, the medical personnel failed to properly implement protocol-driven hand hygiene applications. However, the significant differences between physicians’ and nurses’ self-reports suggest further inquiry is needed to fully explore these discrepancies.


title: Real‐time epidemiology: Understanding the spread of SARS

text: Fitting transmission models to outbreak data allows key epidemiological parameters to be estimated and the impact of control measures to be evaluated. Christl Donnelly and Azra Ghani describe the use of such models in the 2003 SARS epidemic in Hong Kong.


title: Neuroendovascular Treatment of Acute Stroke during Covid-19: A Guide from the Frontlines

text: Since the initial reports surfaced of a novel Coronavirus causing illness and loss of life in Wuhan, China, COVID-19 has rapidly spread across the globe infecting millions and leaving hundreds of thousands dead. As hospitals cope with the influx of COVID-19 patients, new challenges have arisen as healthcare systems care for COVID-19 patients while still providing essential emergency care for patients with acute strokes and acute myocardial infarction. Adding to this complex scenario are new reports that COVID-19 patients are at increased risk of thromboembolic complications including strokes. In this paper, we detail our experience caring for acute stroke patients, and provide some insight into neurointerventional workflow modifications that have helped us adapt to the COVID-19 era.


Mayo Clinic Strategies for COVID-19 Research Response to SARS-CoV-2/COVID-19


title: Overexpression of human virus surface glycoprotein precursors induces cytosolic unfolded protein response in Saccharomyces cerevisiae

text: BACKGROUND: The expression of human virus surface proteins, as well as other mammalian glycoproteins, is much more efficient in cells of higher eukaryotes rather than yeasts. The limitations to high-level expression of active viral surface glycoproteins in yeast are not well understood. To identify possible bottlenecks we performed a detailed study on overexpression of recombinant mumps hemagglutinin-neuraminidase (MuHN) and measles hemagglutinin (MeH) in yeast Saccharomyces cerevisiae, combining the analysis of recombinant proteins with a proteomic approach. RESULTS: Overexpressed recombinant MuHN and MeH proteins were present in large aggregates, were inactive and totally insoluble under native conditions. Moreover, the majority of recombinant protein was found in immature form of non-glycosylated precursors. Fractionation of yeast lysates revealed that the core of viral surface protein aggregates consists of MuHN or MeH disulfide-linked multimers involving eukaryotic translation elongation factor 1A (eEF1A) and is closely associated with small heat shock proteins (sHsps) that can be removed only under denaturing conditions. Complexes of large Hsps seem to be bound to aggregate core peripherally as they can be easily removed at high salt concentrations. Proteomic analysis revealed that the accumulation of unglycosylated viral protein precursors results in specific cytosolic unfolded protein response (UPR-Cyto) in yeast cells, characterized by different action and regulation of small Hsps versus large chaperones of Hsp70, Hsp90 and Hsp110 families. In contrast to most environmental stresses, in the response to synthesis of recombinant MuHN and MeH, only the large Hsps were upregulated whereas sHsps were not. Interestingly, the amount of eEF1A was also increased during this stress response. CONCLUSIONS: Inefficient translocation of MuHN and MeH precursors through ER membrane is a bottleneck for high-level expression in yeast. Overexpression of these recombinant proteins induces the UPR's cytosolic counterpart, the UPR-Cyto, which represent a subset of proteins involved in the heat-shock response. The involvement of eEF1A may explain the mechanism by which only large chaperones, but not small Hsps are upregulated during this stress response. Our study highlights important differences between viral surface protein expression in yeast and mammalian cells at the first stage of secretory pathway.


title: Credibility of self-reported health parameters in elderly population

text: AIM: Examining the credibility of self-reported height, weight, and blood pressure by the elderly population using a tablet in a retirement residence, and examining the influence of health beliefs on the self-reporting credibility. BACKGROUND: Obesity is a major problem with rising prevalence in the western world. Hypertension is also a significant risk factor for cardiovascular diseases. Self-report, remotely from the clinic, becomes even more essential when patients are encouraged to avoid visiting the clinic as during the COVID-19 pandemic. Self-reporting of height and weight is suspected of leading to underestimation of obesity prevalence in the population; however, it has not been well studied in the elderly population. The Health Belief Model tries to predict and explain decision making of patients based on the patient’s health beliefs. METHODS: Residents of a retirement home network filled a questionnaire about their health beliefs regarding hypertension and obesity and self-reported their height, weight, and blood pressure. Blood pressure, height, and weight were then measured and compared to the patients’ self-reporting. FINDINGS: Ninety residents, aged 84.90 ± 5.88, filled the questionnaire. From a clinical perspective, the overall gap between the measured and the self-reported BMI (M = 1.43, SD = 2.72), which represents an absolute gap of 0.74 kilograms and 2.95 centimeters, is expected to have only a mild influence on the physician’s clinical evaluation of the patient’s medical condition. This can allow the physician to estimate their patient’s BMI status before the medical consultation and physical examination upon the patient’s self-reporting. Patients’ dichotomous (normal/abnormal) self-report of their blood pressure condition was relatively credible: positive predictive value (PPV) of 77.78% for normal blood pressure (BP) and 78.57% for abnormal BP. The relatively high PPV of BP self-reporting demonstrates an option for the physician to recognize patients at risk. Regression analysis found no correlation between the anthropometric parameters and the Health Belief Model.


title: The Characteristics of Middle Eastern Respiratory Syndrome Coronavirus Transmission Dynamics in South Korea

text: OBJECTIVES: The outbreak of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) was one of the major events in South Korea in 2015. In particular, this study pays attention to formulating a mathematical model for MERS transmission dynamics and estimating transmission rates. METHODS: Incidence data of MERS-CoV from the government authority was analyzed for the first aim and a mathematical model was built and analyzed for the second aim of the study. A mathematical model for MERS-CoV transmission dynamics is used to estimate the transmission rates in two periods due to the implementation of intensive interventions. RESULTS: Using the estimates of the transmission rates, the basic reproduction number was estimated in two periods. Due to the superspreader, the basic reproduction number was very large in the first period; however, the basic reproduction number of the second period has reduced significantly after intensive interventions. CONCLUSION: It turned out to be the intensive isolation and quarantine interventions that were the most critical factors that prevented the spread of the MERS outbreak. The results are expected to be useful to devise more efficient intervention strategies in the future.


JEPM January 2017—Abstracts


title: Comparison of two multiplex PCR assays for the detection of respiratory viral infections

text: INTRODUCTION: Respiratory viruses are the main causes of upper and lower respiratory tract diseases. Rapid and accurate detection of respiratory viruses is crucial for appropriate patient treatment and prevention of endemic spread. OBJECTIVES: We compared two multiplex polymerase chain reaction (PCR) assays for the detection of respiratory viral pathogens. METHODS: A total of 245 respiratory specimens (229 sputum samples, 14 bronchoalveolar lavage samples, 6 nasal swabs, 3 throat swabs, 7 unknown) were analyzed using two multiplex assays: One‐step RV real‐time PCR (BioSewoom, Seoul, Korea) and Seeplex RV 12 Detection kit (Seegene, Seoul, Korea). The results were further confirmed using sequencing as a reference. RESULTS: Among 245 samples (265 identifications including co‐infections), the identification of respiratory viruses was 44.9% (119/265), 44.2% (117/265) and 45.3% (120/265) by One‐step RV assay, Seeplex RV assay and sequencing, respectively. The concordance rate between One‐step RV assay and sequencing was 95.5% (253/265), and that between Seeplex RV assay and sequencing was 89.8% (238/265) (P = 0.0189). The sensitivities of One‐step RV and Seeplex RV assays were 94.1% [95% confidential interval (CI), 88.3%–97.6%] and 83.3% (95% CI, 75.4%–89.5%), respectively (P = 0.0002). The specificities of One‐step RV and Seeplex RV assays were 96.6% (95% CI, 92.2%–98.9%) and 95.2% (95% CI, 90.3%–98.0%), respectively. CONCLUSION: Although the performances of One‐step RV and Seeplex RV assays were overall comparable, One‐step RV assay showed better sensitivity and concordance with sequencing. One‐step RV assay can be a useful option for respiratory virus testing in clinical laboratories.


title: 69 Membrane alanyl aminopeptidase

text: Publisher Summary This chapter focuses on the structural chemistry of membrane alanyl aminopeptidase (mAAP). The early history of mAAP relates to its role as Cys-Gly dipeptidase or cysteinyl-glycinase. It was proposed that this peptidase activity present in apparently purified RNA preparations contributed to polypeptide biosynthesis by acting in reverse in a sequential fashion. mAAP has a broad substrate specificity removing N-terminal amino acids (Xaa-Xbb-) from almost all unsubstituted oligopeptides and from an amide or arylamide. mAAP is a type II integral membrane protein located on the plasma membrane as an ectoenzyme. The pI is approximately 5. mAAP is widely distributed among species and tissues although it is of greatest abundance in brush border membranes of the kidney, in the mucosal cells of the small intestine and in the liver. It is also present in the lung where it is identical to the pI46 type II alveolar epithelial cell antigen and is located on endothelial cells in blood vessels. On polarized epithelial cells, mAAP is localized to the apical domain and is targeted there through an apical sorting signal thought to be located in the catalytic head group region of the protein.


title: Epidemiological characteristics of the first 100 cases of coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region, China, a city with a stringent containment policy

text: BACKGROUND: Hong Kong (HK) is a densely populated city near the epicentre of the coronavirus disease 2019 (COVID-19) outbreak. Stringent border control together with aggressive case finding, contact tracing, social distancing and quarantine measures were implemented to halt the importation and spread of the virus. METHODS: We performed an epidemiological study using government information covering the first 100 confirmed cases to examine the epidemic curve, incidence, clusters, reproduction number (R(t)), incubation period and time to containment. RESULTS: A total of 93 of the 100 cases were HK residents (6 infected in Mainland China, 10 on the Diamond Princess Cruise). Seven were visitors infected in Mainland China before entering HK. The majority (76%) were aged ≥45 years, and the incidence increased with age (P < 0.001). Escalation of border control measures correlated with a decrease in the proportion (62.5% to 0%) of cases imported from Mainland China, and a reduction in R(t) (1.07 to 0.75). The median incubation period was 4.2 days [95% confidence interval (CI), 4.0–4.5; 5th and 95th percentiles: 1.3 and 14.0). Most clusters with identifiable epidemiological links were households involving 2–4 people. Three medium-spreading events were identified: two from New Year gatherings (6–11 people), and another from environmental contamination of a worship hall (12 people). Despite intensified contact tracing, containment was delayed in 78.9% of cases (mean = 5.96 days, range = 0–24 days). An unusual transmission in a multi-storey building via faulty toilet plumbing was suspected with >100 residents evacuated overnight. Our analysis indicated that faulty plumbing was unlikely to be the source of this transmission. CONCLUSIONS: Timely stringent containment policies minimized the importation and transmission of COVID-19 in HK.


title: Long distance truck drivers and the increasing risk of COVID-19 spread in Uganda

text: Abstract Objectives To examine the patterns of COVID-19 transmission in Uganda. Methods We reviewed press releases from the Uganda Ministry of Health from when the first case was announced on March 22 up to May 29, 2020 a 10-week period. We obtained the press releases from the MoH website and the Twitter handle (@MinofHealthUG). Data include number of persons tested and the categories classified as international arrivals, community members and long distance truck drivers. Results The first cases were international arrivals from Asia and Europe and thereafter community cases emerged. However, in the middle of April 2020, COVID-19 cases were detected among long distance truck drivers. By May 29, 2020, a total of 89, 224 persons had been tested and overall 442 tested positive. Of those that tested positive, majority or 317 (71.8%) were truck drivers, 75 (16.9%) were community cases and 50 (11.3%) were international arrivals. Majority of community cases have been linked to contact with truck drivers. Conclusions The truck drivers are the most frequently diagnosed category, and have become a core group for COVID-19 in Uganda. They have generated significant local transmission which now threatens a full blown epidemic in the country unless strict controls are put in place.


title: Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19

text: BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting–enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case–control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.


title: Early National and Center‐level Changes to Kidney Transplantation in the United States During COVID‐19 Epidemic

text: In March 2020, COVID‐19 spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center‐levels, accounting statistically for waitlist composition. Using SRTR data, we compared data on observed waitlist registrations, waitlist mortality, living‐donor and deceased‐donor kidney transplants (LDKT/DDKT) March 15‐April 30, 2020 to expected events calculated from pre‐epidemic data January 2016‐February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all p<0.001). Only 12 centers performed LDKT March 15‐31; by April 30, 40 centers had resumed LDKT. The decline in new listings and DDKT was greater among states with higher per capita confirmed COVID‐19 cases. The number of waitlist deaths was 2.2‐fold higher than expected in the five states with highest COVID‐19 burden (p<0.001). DCD DDKT and regional/national imports declined nationwide, but most steeply in states with the highest COVID‐19 burden. The COVID‐19 epidemic has resulted in substantial changes to KT; we must adapt and learn rapidly to continue provide safe access to transplantation and limit the growing indirect toll of an already deadly disease.


title: Enteric coronavirus TGEV: partial sequence of the genomic RNA, its organization and expression

text: Abstract The sequence of the 3′-most 8300 nucleotides of the genome RNA of the Purdue-115 strain of the transmissible gastroenteritis virus TGEV, a porcine coronavirus, was determined from cDNA clones. The available sequence corresponds to the part of the genome (total length > 20 kb) expressed through subgenomic mRNAs. The 5 subgenomic and the genomic RNA species detected in TGEV-infected cells form a 3′-coterminal ‘nested’ structure, a unique feature of Coronaviridae. The transcription initiation site of the TGEV subgenomic RNAs appears to involve the hexameric sequence 5′CTAAAC, which is present upstream from each coding region. In addition to the previously identified genes encoding the three structural proteins, E2, E1 and N, two regions, X1 and X2, corresponding to the non-overlapping portion of mRNAs 4 and 3, may code for so far unidentified non-structural polypeptides. The predicted X1 polypeptide (9.2 kDa) is highly hydrophobic. The sequence of the X2 region allows the translation of two non-ovelapping products, i.e., X2a (7.7 kDa).and x2b (18.8 kDa). No RNA species liable to express the extreme 3′ open reading frame X3 was found.


title: Respiratory and facial protection: a critical review of recent literature

text: Summary Infectious micro-organisms may be transmitted by a variety of routes. This is dependent on the particular pathogen and includes bloodborne, droplet, airborne, and contact transmission. Some micro-organisms are spread by more than one route. Respiratory and facial protection is required for those organisms which are usually transmitted via the droplet and/or airborne routes or when airborne particles have been created during ‘aerosol-generating procedures’. This article presents a critical review of the recently published literature in this area that was undertaken by Health Protection Scotland and the Healthcare Infection Society and which informed the development of guidance on the use of respiratory and facial protection equipment by healthcare workers.


title: Carbon nanotube electric immunoassay for the detection of swine influenza virus H1N1

text: A low-cost, label-free, ultra-sensitive electric immunoassay is developed for the detection of swine influenza virus (SIV) H1N1. The assay is based on the excellent electrical properties of single-walled carbon nanotubes (SWCNTs). Antibody–virus complexes influence the conductance of underlying SWCNT thin film, which has been constructed by facile layer-by-layer self-assembly. The basic steps of conventional immunoassay are performed followed by the electric characterization of immunochips at the last stage. The resistance of immunochips tends to increase upon surface adsorption of macromolecules such as poly-l-lysine, anti-SIV antibodies, and SIVs during the assay. The resistance shift after the binding of SIV with anti-SIV antibody is normalized with the resistances of bare devices. The sensor selectivity tests are performed with non-SIVs, showing the normalized resistance shift of 12% as a background. The detection limit of 180 TCID(50)/ml of SIV is obtained suggesting a potential application of this assay as point-of-care detection or monitoring system. This facile CNT-based immunoassay also has the potential to be used as a sensing platform for lab-on-a-chip system.


title: Evaluation of Patients with Community‐Acquired Pneumonia Caused by Zoonotic Pathogens in an Area with a High Density of Animal Farms

text: Intensive animal farming could potentially lead to outbreaks of infectious diseases. Clinicians are at the forefront of detecting unusual diseases, but the lack of specificity of zoonotic disease symptoms makes this a challenging task. We evaluated patients with community‐acquired pneumonia (CAP) with known and unknown aetiology in an area with a high livestock density and a potential association with animal farms in the proximity. Between 2008 and 2009, a period coinciding with a large Q fever outbreak in the Netherlands, patients with CAP were tested for the presence of possible respiratory pathogens. The presence and number of farm animals within 1 km of the patients' home address were assessed using geographic information system (GIS) and were compared between cases and age‐matched control subjects. Of 408 patients with CAP, pathogens were detected in 275 (67.4%) patients. The presence of sheep and the number of goats were associated with CAP caused by Coxiella burnetii in a multiple logistic regression model (P < 0.05). CAP with unknown aetiology was not associated with the presence of animal farms (P > 0.10). The use of GIS in combination with aetiology of CAP could be potentially used to target diagnostics and to identify outbreaks of rare zoonotic disease.


title: Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human papillomavirus (HPV) E5

text: Abstract Despite the availability of prophylactic vaccines the burden of human papillomavirus (HPV) associated malignancy remains high and there is a need to develop additional therapeutic strategies to complement vaccination. We have previously shown that the poorly characterised E5 oncoprotein forms a virus-coded ion channel or viroporin that was sensitive to the amantadine derivative rimantadine. We now demonstrate that alkylated imino sugars, which have antiviral activity against a number of viruses, inhibit E5 channel activity in vitro. Using molecular modelling we predict that imino sugars intercalate between E5 protomers to prevent channel oligomerisation. We explored the ability of these viroporin inhibitors to block E5-mediated activation of mitogenic signalling in keratinocytes. Treatment with either rimantadine or imino sugars prevented ERK-MAPK phosphorylation and reduced cyclin B1 expression in cells expressing E5 from a number of high-risk HPV types. Moreover, viroporin inhibitors also reduced ERK-MAPK activation and cyclin B1 expression in differentiating primary human keratinocytes containing high-risk HPV18. These observations provide evidence of a key role for E5 viroporin function during the HPV life cycle. Viroporin inhibitors could be utilised for stratified treatment of HPV associated tumours prior to virus integration, or as true antiviral therapies to eliminate virus prior to malignant transformation.


title: Molecular diagnostics in virology

text: Abstract Molecular biology has significantly improved diagnosis in the field of clinical virology. Virus discovery and rapid implementation of diagnostic tests for newly discovered viruses has strongly beneficiated from the development of molecular techniques. Viral load and antiviral resistance or subtyping assays are now part of the biological monitoring of patients chronically infected by human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and CMV. It will be important to add to this panel assays for other viruses of the herpesviridae family. Qualitative assays for the detection of blood-borne viruses have increased safety of blood donation and organ transplantation. Screening of other blood-borne viruses (parvovirus B19, HAV), multiplexing of detection and test automation to improve practicability and reduce costs will be the next steps. A major evolution in the near future will be the generalization of NAT for the diagnosis of viral etiology in patients, mostly with respiratory, CNS or gastro-intestinal diseases. Major technical improvements have been made to avoid obstacles that still limit this generalization, i.e. genetic variability of viruses, multiplex detection, contamination risk. Commercial offers already exist but menus must be extended to limit the validation and documentation work associated with home-brew assays. Real-time amplification has allowed the development of new NAT platforms but automation and integration of all steps of the reaction are still required to reduce hands-on-time, time-to-result and costs, and to increase throughput.


title: Predicting sub-Golgi localization of type II membrane proteins

text: Motivation: Recent research underlines the importance of finegrained knowledge on protein localization. In particular, subcompartmental localization in the Golgi apparatus is important, for example, for the order of reactions performed in glycosylation pathways or the sorting functions of SNAREs, but is currently poorly understood. Results: We assemble a dataset of type II transmembrane proteins with experimentally determined sub-Golgi localizations and use this information to develop a predictor based on the transmembrane domain of these proteins, making use of a dedicated proteinstructure based kernel in an SVM. Various applications demonstrate the power of our approach. In particular, comparison with a large set of glycan structures illustrates the applicability of our predictions on a ‘glycomic’ scale and demonstrates a significant correlation between sub-Golgi localization and the ordering of different steps in glycan biosynthesis. Contact: roeland.vanham@wur.nl Supplementary information: Supplementary data are available at Bioinformatics online.


title: The causes of false-positives encountered during the screening of old-world primates for antibodies to human and simian retroviruses by ELISA

text: Abstract Sera from 526 old-world primates representing 50 different species were screened by ELISA for antibodies to human T-lymphotropic viruses I and III, and simian retrovirus type 1 (SRV-1). About onefourth of the sera were positive by ELISA. There was a tendency, however, for the same sera to be positive for all three human and simian retroviruses. Only about one in five of the ELISA antibodypositive sera were confirmed to be positive by Western blotting. False-positive ELISA antibody tests were particularly common among sera from mandrills, crab-eating macaques, lion-tailed macaques, African green monkeys, and DeBrazza's and moustached guenons. Sera that were falsely positive in ELISA antibody tests to the three human and simian retroviruses were found to contain antibodies that reacted at comparable intensity with feline leukemia, infectious peritonitis and panleukopenia viruses. The false anti-viral activity of these sera was found to be due to antibodies that reacted with non-viral proteins that were copurified with all five virus preparations. These proteins were present in normal cat and human cells used to grow the various viruses and in gelatin. The implications of nonspecific cell-protein antibodies in primate sera were discussed in the light of this and previous seroepidemiologic studies of man and old-world monkeys.


title: The Burden and Etiology of Community-Onset Pneumonia in the Aging Japanese Population: A Multicenter Prospective Study

text: BACKGROUND: The increasing burden of pneumonia in adults is an emerging health issue in the era of global population aging. This study was conducted to elucidate the burden of community-onset pneumonia (COP) and its etiologic fractions in Japan, the world’s most aged society. METHODS: A multicenter prospective surveillance for COP was conducted from September 2011 to January 2013 in Japan. All pneumonia patients aged ≥15 years, including those with community-acquired pneumonia (CAP) and health care-associated pneumonia (HCAP), were enrolled at four community hospitals on four major islands. The COP burden was estimated based on the surveillance data and national statistics. RESULTS: A total of 1,772 COP episodes out of 932,080 hospital visits were enrolled during the surveillance. The estimated overall incidence rates of adult COP, hospitalization, and in-hospital death were 16.9 (95% confidence interval, 13.6 to 20.9), 5.3 (4.5 to 6.2), and 0.7 (0.6 to 0.8) per 1,000 person-years (PY), respectively. The incidence rates sharply increased with age; the incidence in people aged ≥85 years was 10-fold higher than that in people aged 15-64 years. The estimated annual number of adult COP cases in the entire Japanese population was 1,880,000, and 69.4% were aged ≥65 years. Aspiration-associated pneumonia (630,000) was the leading etiologic category, followed by Streptococcus pneumoniae-associated pneumonia (530,000), Haemophilus influenzae-associated pneumonia (420,000), and respiratory virus-associated pneumonia (420,000), including influenza-associated pneumonia (30,000). CONCLUSIONS: A substantial portion of the COP burden occurs among elderly members of the Japanese adult population. In addition to the introduction of effective vaccines for S. pneumoniae and influenza, multidimensional approaches are needed to reduce the pneumonia burden in an aging society.


title: The Role of Zinc in Antiviral Immunity

text: Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections.


title: Virtual ligand screening: strategies, perspectives and limitations

text: In contrast to high-throughput screening, in virtual ligand screening (VS), compounds are selected using computer programs to predict their binding to a target receptor. A key prerequisite is knowledge about the spatial and energetic criteria responsible for protein–ligand binding. The concepts and prerequisites to perform VS are summarized here, and explanations are sought for the enduring limitations of the technology. Target selection, analysis and preparation are discussed, as well as considerations about the compilation of candidate ligand libraries. The tools and strategies of a VS campaign, and the accuracy of scoring and ranking of the results, are also considered.


title: Publications in ISI-indexed public health journals from mainland China, Hong Kong and Taiwan during 1999–2008

text: BACKGROUND: There has been a steady increase in China’s annual research output. We aimed to investigate the research output in public health from 3 major regions of China: mainland China (ML), Hong Kong (HK) and Taiwan (TW). MATERIAL/METHODS: We retrieved papers published in 105 public health-related journals from ML, HK and TW with the applications of the ISI Web of Knowledge database. The total papers, impact factor, times cited, papers published in the highest impact factor journals, and most often published journals were analyzed for quantity and quality comparisons among the 3 regions. RESULTS: Totally, 2587 papers were published during 1999–2008, including 1089 (42.1%) from ML, 471 (18.2%) from HK, and 1027 (39.7%) from TW. The total annual number of papers from the 3 regions increased significantly, from 140 in 1999 to 424 in 2008. The average impact factor of papers from TW (2.588) was higher than those from HK (2.531) and ML (1.568). The average number of times cited of each paper from TW was 8.84, followed by 8.34 from HK and 5.90 from ML. Excluding publications in Biomedical and Environmental Sciences, papers from ML had higher average IF and average times cited. TW had the most articles published in the highest impact factor journals, and HK had the highest total IF of most often published journals. CONCLUSIONS: The total number of papers in public health from China increased significantly during 1999–2008. ML contributed the highest annual paper output compared with HK and TW, but papers from ML are more often locally published and less frequently cited.


title: A protocol for acute stroke unit care during the COVID-19 pandemic: Acute stroke unit care during COVID-19

text: BACKGROUND: Acute stroke unit (ASU) care is proven to reduce mortality and morbidity. During the COVID-19 crisis, established physical units and care practices within existing physical units are likely to be disrupted. Stroke patients with possible suspected COVID-19 infection may be isolated in other wards outside the ASU. METHODS: Our hospital developed an adapted ASU protocol which includes key elements for stroke unit care, can be utilized by staff not familiar with stroke care with minimal training and can be implemented in various settings. RESULTS: The adapted protocol has 3 categories of Acute monitoring (neurological observations, blood pressure and input-output monitoring, investigations and specific post-reperfusion issues), Stroke complications (focusing on 5 common complications) and Unified team (describing daily check-ins, patient education, communication, discharge planning and post-discharge support). CONCLUSIONS: Details are presented in the article in a format that it can be adopted by other centers facing similar issues in order to ensure ASU care is not compromised.


title: Preclinical evaluation of a mercaptobenzamide and its prodrug for NCp7-targeted inhibition of human immunodeficiency virus

text: Abstract Although the effective use of highly active antiretroviral therapy results in the suppression of virus production in infected individuals, it does not eliminate the infection and low level virus production in cells harboring virus in sanctuary sites. Thus, the continued search for new antiretroviral agents with unique and different mechanisms of HIV inhibition remains critical, and compounds that can reduce the level of virus production from cells already infected with HIV, as opposed to preventing de novo infection, would be of great benefit. A mercaptobenzamide (MDH-1-38) and its prodrug (NS1040) are being developed as potential therapeutic compounds targeting the zinc finger of HIV nucleocapsid. In the presence of esterase enzymes, NS1040 is designed to be converted to MDH-1-38 which has antiviral activity. While we presume that NS1040 is rapidly converted to MDH-1-38 in all experiments, the two compounds were tested side-by-side to determine whether the presence of a prodrug affects the antiviral activity or mechanism of action. The two compounds were evaluated against a panel of HIV-1 clinical isolates in human PBMCs and monocyte-macrophages and yielded EC50 values ranging from 0.7 to 13 μM with no toxicity up to 100 μM. MDH-1-38 and NS1040 remained equally active in human PBMCs in the presence of added serum proteins as well as against HIV-1 isolates resistant to reverse transcriptase, integrase or protease inhibitors. Cell-based and biochemical mechanism of antiviral action assays demonstrated MDH-1-38 and NS1040 were virucidal at concentrations of 15 and 50 μM, respectively. Cell to cell transmission of HIV in multiple passages was significantly reduced in CEM-SS and human PBMCs by reducing progeny virus infectivity at compound concentrations greater than 2 μM. The combination of either MDH-1-38 or NS1040 with other FDA-approved HIV drugs yielded additive to synergistic antiviral interactions with no evidence of antiviral antagonism or synergistic toxicity. Serial dose escalation was used in attempts to select for HIV strains resistant to MDH-1-38 and NS1040. Virus at several passages failed to replicate in cells treated at increased compound concentrations, which is consistent with the proposed mechanism of action of the virus inactivating compounds. Through 14 passages, resistance to the compounds has not been achieved. Most HIV inhibitors with mechanism of antiviral action targeting a viral protein would have selected for a drug resistant virus within 14 passages. These studies indicate that these NCp7-targeted compounds represent new potent anti-HIV drug candidates which could be effectively used in combination with all approved anti-HIV drugs.


title: Structurally- and dynamically-driven allostery of the chymotrypsin-like proteases of SARS, Dengue and Zika viruses

text: Abstract Coronavirus 3C-like and Flavivirus NS2B-NS3 proteases utilize the chymotrypsin fold to harbor their catalytic machineries but also contain additional domains/co-factors. Over the past decade, we aimed to decipher how the extra domains/co-factors mediate the catalytic machineries of SARS 3C-like, Dengue and Zika NS2B-NS3 proteases by characterizing their folding, structures, dynamics and inhibition with NMR, X-ray crystallography and MD simulations, and the results revealed: 1) the chymotrypsin fold of the SARS 3C-like protease can independently fold, while, by contrast, those of Dengue and Zika proteases lack the intrinsic capacity to fold without co-factors. 2) Mutations on the extra domain of SARS 3C-like protease can transform the active catalytic machinery into the inactive collapsed state by structurally-driven allostery. 3) Amazingly, even without detectable structural changes, mutations on the extra domain are sufficient to either inactivate or enhance the catalytic machinery of SARS 3C-like protease by dynamically-driven allostery. 4) Global networks of correlated motions have been identified: for SARS 3C-like protease, N214A inactivates the catalytic machinery by decoupling the network, while STI/A and STIF/A enhance by altering the patterns of the network. The global networks of Dengue and Zika proteases are coordinated by their NS2B-cofactors. 5) Natural products were identified to allosterically inhibit Zika and Dengue proteases through binding a pocket on the back of the active site. Therefore, by introducing extra domains/cofactors, nature develops diverse strategies to regulate the catalytic machinery embedded on the chymotrypsin fold through folding, structurally- and dynamically-driven allostery, all of which might be exploited to develop antiviral drugs.


title: An evidence mapping and analysis of registered COVID-19 clinical trials in China

text: BACKGROUND: This article aims to summarize the key characteristics of registered trials of 2019 novel coronavirus (COVID-19), in terms of their spatial and temporal distributions, types of design and interventions, and patient characteristics among others. METHODS: A comprehensive search of the registered COVID-19 trials has been performed on platforms including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (WHO ICTRP), Chinese Clinical Trials Registry (CHiCTR), Australian Clinical Trials Registry, Britain’s National Research Register (BNRR), Current Control Trials (CCT), and Glaxo Smith Kline Register. Trials registered at the first 8 weeks of the COVID-19 outbreak are included, without language restrictions. For each study, the registration information, study design, and administrator information are collected and summarized. RESULTS: A total of 220 registered trials were evaluated as of February 27, 2020. Hospital-initiated trials were the majority and account for 80% of the sample. Among the trials, pilot studies and phase 4 trials are more common and represent 35% and 19.1% of the sample, respectively. The median sample size of the registered trials is 100, with interquartile range 60–240. Further, 45.9% of the trials mentioned information on a data monitoring committee. 54.5% of the trials did not specify the disease severity among patients they intend to recruit. Four types of interventions are most common in the experimental groups across the registered studies: antiviral drugs, Traditional Chinese Medicine (TCM), biological agents, and hormone drugs. Among them, the TCM and biological agents are frequently used in pilot study and correspond to a variety of primary endpoints. In contrast, trials with antiviral drugs have more targeted primary outcomes such as “COVID-19 nucleic acid test” and “28-day mortality.” CONCLUSIONS: We provide an evidence mapping and analysis of registered COVID-19 clinical trials in China. In particular, it is critical for ongoing and future studies to refine their research hypothesis and better identify their intervention therapies and the corresponding primary outcomes. It is also imperative for multiple public health divisions and research institutions to work together for integrative clinical data capture and sharing, with a common objective of improving future studies that evaluate COVID-19 interventions.


title: Assessment of knowledge, attitudes and perceptions regarding Ebola disease in healthcare workers from a tertiary care hospital in Romania

text: Abstract Objectives The National Institute for Infectious Diseases ‘Prof. Dr. Matei Balș’ was the designated centre for managing Ebola alerts in Romania during the 2014 African outbreak. We surveyed Ebola knowledge, attitudes and perceptions (KAP) among the institute's healthcare workers. Study design This was a cross-sectional survey. Methods The study consisted of a self-administered paper-based anonymous questionnaire that included 24 closed-item questions and two scales of personal concern. Results Respondents were generally well informed; compared to nurses, doctors recorded a 1.9-fold higher rate of correct responses regarding Ebola transmission (P < 0.001), but both nurses and doctors correctly identified Ebola's aetiological agent. Nurses perceived higher personal (P = 0.008) and family (P < 0.001) risk than doctors. Respondents reporting high perceived risks were more likely to be less informed about Ebola (P = 0.019) and its prevention options (P = 0.033). Males were 6.7-fold more likely to volunteer than females (P = 0.001) and so were graduates of higher rather than lower education (1.5-fold more likely, P = 0.017) and doctors than nurses (1.7-fold more likely, P = 0.018). The institute ranked first among sources of information on Ebola; respondents who had received Ebola training in the institute 2 years previously were 1.2–1.3 times more likely to correctly identify transmission routes. Conclusions We have characterised KAP on Ebola disease among Romanian healthcare workers from a tertiary care hospital in Bucharest. Nurses, specialist physicians and laboratory personnel may need more frequent retraining than residents and senior physicians.


title: Loop‐mediated isothermal amplification: an emerging technology for detection of fish and shellfish pathogens

text: Fish and shellfish diseases are a constant threat to the sustainability and economic viability of aquaculture. Early diagnosis plays a vital role in management of fish and shellfish diseases. Traditionally, various biochemical and serological tests have been used for fish disease diagnosis. However, the time and expertise required for such diagnoses makes it difficult for aquaculturists to easily adopt them under production conditions. Polymerase chain reaction and probe‐based nucleic acid detection have become increasingly popular in fish and shellfish diagnostics. Recently, a novel technique called loop‐mediated isothermal amplification (LAMP) has been developed, which is highly sensitive and rapid. LAMP has been used for the detection of bacterial, viral, fungal and parasitic diseases in both animal and plants. In aquaculture, LAMP‐based detection of pathogens like Edwardsiella tarda, E. ictaluri, Nocardia seriolae, Tetracapsuloides bryosalmonae, white spot syndrome virus and infectious haematopoietic necrosis virus have been reported. In this review, the application of LAMP for the detection of aquaculture‐associated pathogens is discussed.


title: Misinformation of COVID-19 on the Internet: Infodemiology Study

text: BACKGROUND: The internet has become an important source of health information for users worldwide. The novel coronavirus caused a pandemic search for information with broad dissemination of false or misleading health information. OBJECTIVE: The aim of this study was to evaluate the quality and readability of online information about the coronavirus disease (COVID-19), which was a trending topic on the internet, using validated instruments and relating the quality of information to its readability. METHODS: The search was based on the term “Wuhan Coronavirus” on the Google website (February 6, 2020). At the search time, the terms “COVID-19” or “SARS-CoV-2” (severe acute respiratory syndrome coronavirus 2) did not exist. Critical analysis was performed on the first 110 hits using the Health on the Net Foundation Code of Conduct (HONcode), the Journal of the American Medical Association (JAMA) benchmark, the DISCERN instrument, and Google ranking. RESULTS: The first 110 websites were critically analyzed, and only 1.8% (n=2) of the websites had the HONcode seal. The JAMA benchmark showed that 39.1% (n=43) of the websites did not have any of the categories required by this tool, and only 10.0% (11/110) of the websites had the four quality criteria required by JAMA. The DISCERN score showed that 70.0% (n=77) of the websites were evaluated as having a low score and none were rated as having a high score. CONCLUSIONS: Nonhealth personnel and the scientific community need to be aware about the quality of the information they read and produce, respectively. The Wuhan coronavirus health crisis misinformation was produced by the media, and the misinformation was obtained by users from the internet. The use of the internet has a risk to public health, and, in cases like this, the governments should be developing strategies to regulate health information on the internet without censuring the population. By February 6, 2020, no quality information was available on the internet about COVID-19.


title: Immunohistochemical study of porcine lung lesions associated with Pasteurella multocida

text: Abstract Infectious bronchopneumonia is a widespread disease in modern commercial pig production and Pasteurella multocida is frequently associated with the lesions. To evaluate porcine lung lesions associated with P. multocida, populations of inflammatory cells were examined by immunohistochemistry in necrotic lung lesions from nine pigs and exudative lung lesions from eleven pigs. Lungs from five pigs served as controls. All cases were selected from naturally infected pigs using co-infection based criteria to make them as comparable as possible. The inflammatory cells demonstrated by immunohistochemistry were T-lymphocytes (CD3+, CD4+ and CD8+ subsets), B-lymphocytes, neutrophils, macrophages, and IgA+, IgM+ and IgG+ cells. The results showed that (1) a significant increase in all inflammatory cells was found in lesions associated with P. multocida, (2) necrotic lesions had a larger number of CD3+ T-lymphocytes and IgA+ cells, and (3) cases with exudative lesions had a more CD8+ T-lymphocytes, B-lymphocytes, macrophages and neutrophils. No differences in the numbers of CD4+ T-lymphocytes, IgG+ and IgM+ positive cells were found between necrotic and exudative cases. The results show that P. multocida significantly alters the inflammatory response in the lung and that lesions associated with P. multocida display diverse inflammatory responses according to their distinct morphological pattern.


title: Preoperative Function and Gender Predict Pattern of Functional Recovery After Hip and Knee Arthroplasty

text: Abstract Gender, preoperative function, and other variables were explored as predictors of recovery after total hip and knee arthroplasty. One hundred fifty-two subjects (63.8 ± 10.2 years) were repeatedly assessed in the first 4 postoperative months. Average recovery curves for the Western Ontario and McMaster Universities Osteoarthritis Index, 6-minute walk test, and timed up and go test were characterized using hierarchical linear modeling. Recovery predictors were sequentially modeled after validation of the basic developmental models. Gender was a significant predictor (P ≤ .003) of physical performance measure scores 1 week after surgery. Thereafter, men and women had similar rates of improvement. Preoperative score was a significant predictor (P ≤ .001) in all models. Patients' and surgeons' expectations of outcome need to take preoperative function into account.


title: Altered immune function in demyelinative disease

text: Abstract Experimentally induced demyelination has an autoimmune origin in some mouse models and is somehow virally induced in others. In June, invited participants in a Kroc Foundation workshop discussed the damaging mechanisms involved and their relevance to an understanding of multiple sclerosis and human encephalomyelitis.


Editorial: Emerging Viruses: Host Immunity and Novel Therapeutic Interventions


title: Comparison of the genome organization of toro- and coronaviruses: Evidence for two nonhomologous RNA recombination events during berne virus evolution

text: Abstract Recently, toroviruses and coronaviruses have been found to be ancestrally related by divergence of their polymerase and envelope proteins from common ancestors. In addition, their genome organization and expression strategy, which involves the synthesis of a 3′-coterminal nested set of mRNAs, are comparable. Nucleotide sequence analysis of the genome of the torovirus prototype, Berne virus (BEV), has now revealed the results of two independent nonhomologous RNA recombinations during torovirus evolution. Berne virus open reading frame (ORF) 4 encodes a protein with significant sequence similarity (30–35% identical residues) to a part of the hemagglutinin esterase proteins of corona-viruses and influenza virus C. The sequence of the C-terminal part of the predicted BEV polymerase ORF1a product contains 31–36% identical amino acids when compared with the sequence of a nonstructural 30 32K corona-virus protein. The cluster of coronaviruses which contains this nonstructural gene expresses it not as a part of their polymerase, but by synthesizing an additional subgenomic mRNA.


title: Family Tetraviridae

text: Publisher Summary This chapter describes the Tetraviridae family. The virions of the Betatetravirus genus are nonenveloped, roughly spherical, of about 40 nm in diameter and exhibit T = 4 icosahedral shell quasi-symmetry. The genome consists of ssRNA and the viruses in the genus Betatetravirus have monopartite genomes. Betatetraviruses replicate in the cytoplasm and has three distinct types of genomic organization. Most of the members of the group are serologically interrelated but distinguishable. The majority of the isolates were identified on the basis of their serological reaction with antiserum raised against NβV. All the virus species were isolated from Lepidoptera species (moths and butterflies), principally from Saturniid, Limacodid, and Noctuid moths, and no replication in other animals has been detected. In larvae, virus replication is restricted predominantly to the cells of the midgut. With the exception of PrV, no infections by members of the Betatetravirus genus have been achieved in cultured cells, even when gRNA was transfected directly into cells. At high host densities, horizontal spread appears to be the major route of infection. Suggestive evidence exists for vertical transmission, which could be responsible for the observed persistence of tetraviruses within insect populations. The viruses replicate primarily in the cytoplasm of gut cells of several Lepidoptera species. The virons of omegatetravirus genus are nonenveloped, roughly spherical, about 40 nm in diameter and exhibit T = 4 icosahedral shell quasi-symmetry. Unlike viruses in the genus Betatetravirus, viruses in the genus Omegatetravirus have bipartite genomes. As with the betatetraviruses, omegatetraviruses replicate in the cytoplasm and studies in tissue culture cells show that the HaSV replicase is localized within the cytoplasm and associates with membranes derived from the endocytic pathway.


title: Face the COVID‐19 emergency: measures applied in an Italian Dermatologic Clinic

text: We have read with great interest the article by Radi et al. which reported the measures applied in order to limit the spread of coronavirus‐infection in their dermatological clinic. Particularly they described all the exceptional precautionary measures adopted in order to face COVID‐19‐emergency and to reduce the spread of infection. Herein we report the experience of our dermatologic Clinic (University of Naples Federico II) which has a very large catchment area and a high number of annually visits (59000 visits in the 2019).


title: Middle East Respiratory Syndrome

text: The Middle East Respiratory Syndrome (MERS) is a newly recognized highly lethal respiratory disease caused by a novel single stranded, positive sense RNA betacoronavirus (MERS-CoV). Dromedary camels, host species for MERS-CoV are implicated in the direct or indirect transmission to humans, although the exact mode of transmission remains unknown. First isolated from a patient who died from a severe respiratory illness in June 2012 in Jeddah, Saudi Arabia, as of 16 February 2015, 983 laboratory-confirmed cases of MERS-CoV (360 deaths; 36.6% mortality) were reported to the WHO. Cases have been acquired in both the community and hospitals with limited human-to-human transmission reported in the community. Whilst the majority of MERS cases have occurred in Saudi Arabia and the United Arab Emirates, cases have been reported from Europe, USA and Asia in people who traveled from the Middle East or their contacts. Clinical features of MERS range from asymptomatic or mild disease to acute respiratory distress syndrome and multi-organ failure resulting in death, especially in individuals with underlying co-morbidities. There is no specific drug treatment for MERS and infection prevention and control measures are crucial to prevent spread of MERS-CoV in health care facilities. MERS-CoV continues to be an endemic,low level public health threat. However, the concern remains that the virus could mutate to exhibit increased interhuman transmissibility, increasing pandemic potential. Our seminar presents an overview of current knowledge and perspectives on the epidemiology, virology, mode of transmission, pathogen-host responses, clinical features, diagnosis and development of new drugs and vaccines.


title: Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study

text: BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5–29·1) of the health-care workforce needing to provide care for children aged 3–12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8–15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.


title: The regulation of HIV‐1 transcription: Molecular targets for chemotherapeutic intervention

text: The regulation of transcription of the human immunodeficiency virus (HIV) is a complex event that requires the cooperative action of both viral and cellular components. In latently infected resting CD4(+) T cells HIV‐1 transcription seems to be repressed by deacetylation events mediated by histone deacetylases (HDACs). Upon reactivation of HIV‐1 from latency, HDACs are displaced in response to the recruitment of histone acetyltransferases (HATs) by NF‐κB or the viral transcriptional activator Tat and result in multiple acetylation events. Following chromatin remodeling of the viral promoter region, transcription is initiated and leads to the formation of the TAR element. The complex of Tat with p‐TEFb then binds the loop structures of TAR RNA thereby positioning CDK9 to phosphorylate the cellular RNA polymerase II. The Tat‐TAR‐dependent phosphorylation of RNA polymerase II plays an important role in transcriptional elongation as well as in other post‐transcriptional events. As such, targeting of Tat protein (and/or cellular cofactors) provide an interesting perspective for therapeutic intervention in the HIV replicative cycle and may afford lifetime control of the HIV infection. © 2006 Wiley Periodicals, Inc. Med Res Rev, 26, No. 5, 595–625, 2006


title: Proteomics-based identification of plasma proteins and their association with the host–pathogen interaction in chronic typhoid carriers

text: Summary Background Current diagnostic tests are inadequate to detect typhoid cases, as well as the chronic carrier state, the sole reservoir of Salmonella enterica serovar Typhi. The current study was conducted to find new molecular signatures of pathogen/disease to understand the mechanism behind the host–pathogen interaction in enteric fever. Methods Proteomics-based studies were done to determine the expression of differentially expressed proteins in the plasma of controls, acute typhoid cases, and chronic typhoid carriers. Further, transcriptome-based analysis using reverse-transcriptase PCR (RT-PCR) was done in controls, acute typhoid cases, and chronic typhoid carriers. Results Results showed the upregulation of proprotein convertase subtilisin, furin, haptoglobin, and albumin in the plasma of chronic typhoid carriers. The elevation in mRNA expression of four differentially expressed proteins confirms the changes at the transcriptional level. Further, the increase in albumin and haptoglobin in chronic typhoid carriers shows their role in free radical generation, inflammation, and monocyte cell signaling. Conclusion Through proteomics techniques, this study identified four proteins in the chronic typhoid carrier host that may have a role in the disease pathogenesis of enteric fever.


Asthme et COVID-19: une population à risque?