title: Multiple changes in sialic acid biology during human evolution

text: Humans are genetically very similar to “great apes”, (chimpanzees, bonobos, gorillas and orangutans), our closest evolutionary relatives. We have discovered multiple genetic and biochemical differences between humans and these other hominids, in relation to sialic acids and in Siglecs (Sia-recognizing Ig superfamily lectins). An inactivating mutation in the CMAH gene eliminated human expression of N-glycolylneuraminic acid (Neu5Gc) a major sialic acid in “great apes”. Additional human-specific changes have been found, affecting at least 10 of the <60 genes known to be involved in the biology of sialic acids. There are potential implications for unique features of humans, as well as for human susceptibility or resistance to disease. Additionally, metabolic incorporation of Neu5Gc from animal-derived materials occurs into biotherapeutic molecules and cellular preparations - and into human tissues from dietary sources, particularly red meat and milk products. As humans also have varying and sometime high levels of circulating anti-Neu5Gc antibodies, there are implications for biotechnology products, and for some human diseases associated with chronic inflammation.


title: Experimental and theoretical studies of solvent effects on the hydrogen bonds in homoconjugated cations of substituted 4-halo (Cl,Br) pyridine N-oxide derivatives

text: Abstract Hydrogen bond OHO-type bridges formed between six substituted 4-halo (Cl,Br) pyridine N-oxide systems and their simple cations have been investigated by using the potentiometric titration method. The formation constants of these complexes (expressed as lg K BHB + ) have been determined in two non-aqueous aprotic solvents with different polarity, i.e., acetone (AC) and acetonitrile (AN). It has been observed that tri- and tetra-substituted pyridine N-oxides [B] and their cationic acids [BH+] form stable homocomplexed cations [BHB+] stabilized by O⋯H⋯O bridges in both solvents used. It has been found that the most stable homocomplexed system is formed by 3,5-dimethyl-4-chloropyridine N-oxide (3,5Me24ClPyO). The lg K BHB + values for this compound in acetone and acetonitrile are 3.15 and 2.82, respectively. Furthermore, by using ab initio methods at the RHF and MP2 levels utilizing the Gaussian 6-31++G∗∗ basis set, the energies of formation of the homocomplexed cations and Gibbs free energies have been determined in vacuo. The calculated energy parameters in vacuo have been compared with the cationic homoconjugation constants determined potentiometrically in acetone and acetonitrile to establish a correlation between these magnitudes. Additionally, the results of potentiometric measurements have been used to determine the acidity constants of the conjugate acids of N-oxides.


COVID-19: la vulnerabilidad en el ojo del huracán


title: Climate Change and Human Health Impacts in the United States: An Update on the Results of the U.S. National Assessment

text: The health sector component of the first U.S. National Assessment, published in 2000, synthesized the anticipated health impacts of climate variability and change for five categories of health outcomes: impacts attributable to temperature, extreme weather events (e.g., storms and floods), air pollution, water- and food-borne diseases, and vector- and rodent-borne diseases. The Health Sector Assessment (HSA) concluded that climate variability and change are likely to increase morbidity and mortality risks for several climate-sensitive health outcomes, with the net impact uncertain. The objective of this study was to update the first HSA based on recent publications that address the potential impacts of climate variability and change in the United States for the five health outcome categories. The literature published since the first HSA supports the initial conclusions, with new data refining quantitative exposure–response relationships for several health end points, particularly for extreme heat events and air pollution. The United States continues to have a very high capacity to plan for and respond to climate change, although relatively little progress has been noted in the literature on implementing adaptive strategies and measures. Large knowledge gaps remain, resulting in a substantial need for additional research to improve our understanding of how weather and climate, both directly and indirectly, can influence human health. Filling these knowledge gaps will help better define the potential health impacts of climate change and identify specific public health adaptations to increase resilience.


title: NEUROVIRULENCE AND PERSISTENCY OF MOUSE HEPATITIS VIRUSES IN RATS 1 1 Supported by the Deutsche Forschungsgemeinschaft and Hertie-Stiftung

text: ABSTRACT The murine coronavirus JHM induces in weanling rats different types of central nervous diseases ranging from an acute panencephalitis to a late demyelinating encephalomyelitis. The occurrence and rate of these different disease types is associated with the virus variant used for inoculation. Except for MHV 2, neurovirulence was not observed in four other murine coronavirus strains. The relationship of these coronaviruses to JHM was investigated by cross neutralization and oligonucleotide maps of their genomic RNA.


title: Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza

text: The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18–3.77; P = .01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.


Respuesta a “Documento de consenso de la traqueotomía en pacientes con COVID 19”


title: Autologous Antibody Capture to Enrich Immunogenic Viruses for Viral Discovery

text: Discovery of new viruses has been boosted by novel deep sequencing technologies. Currently, many viruses can be identified by sequencing without knowledge of the pathogenicity of the virus. However, attributing the presence of a virus in patient material to a disease in the patient can be a challenge. One approach to meet this challenge is identification of viral sequences based on enrichment by autologous patient antibody capture. This method facilitates identification of viruses that have provoked an immune response within the patient and may increase the sensitivity of the current virus discovery techniques. To demonstrate the utility of this method, virus discovery deep sequencing (VIDISCA-454) was performed on clinical samples from 19 patients: 13 with a known respiratory viral infection and 6 with a known gastrointestinal viral infection. Patient sera was collected from one to several months after the acute infection phase. Input and antibody capture material was sequenced and enrichment was assessed. In 18 of the 19 patients, viral reads from immunogenic viruses were enriched by antibody capture (ranging between 1.5x to 343x in respiratory material, and 1.4x to 53x in stool). Enriched reads were also determined in an identity independent manner by using a novel algorithm Xcompare. In 16 of the 19 patients, 21% to 100% of the enriched reads were derived from infecting viruses. In conclusion, the technique provides a novel approach to specifically identify immunogenic viral sequences among the bulk of sequences which are usually encountered during virus discovery metagenomics.


Lessons from a pandemic on practices versus products in agriculture


title: Opportunistic and fungal infections of the lung

text: Abstract Opportunistic infections are a major cause of morbidity and mortality in severely immunocompromised patients, such as those receiving chemotherapy or with haematological malignancy, aplastic anaemia or HIV infection, or recipients of solid-organ or stem cell transplants. In addition, the increasing use of biological therapies will result in more patients at risk of opportunistic infections, albeit to a lesser degree than classic causes of immunocompromise. The type and degree of immune defect dictates the profile of potential opportunistic pathogens; T-cell mediated defects increase the risk of viral (cytomegalovirus and respiratory viruses) and Pneumocystis jirovecii infections, whereas neutrophil defects are associated with bacterial pneumonia and invasive aspergillosis. However, patients often have combinations of immune defects and a wide range of other opportunistic infections can cause pneumonia. The radiological pattern of disease (best assessed by CT scan) and speed of onset also help identify the likely pathogen(s), which can then be supported by targeted investigation including early use of bronchoscopy in selected patients. Rapid and expert clinical assessment can identify the most likely pathogens, which can then be treated aggressively and so provide the best opportunity for a positive outcome.


title: Proteolytic activation of the SARS-coronavirus spike protein: Cutting enzymes at the cutting edge of antiviral research

text: The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on “From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.”


Interdisciplinarity and Infectious Diseases: An Ebola Case Study


title: Pathology of the Exotic Companion Mammal Gastrointestinal System

text: A variety of disease agents can affect the gastrointestinal tract of the exotic companion mammal, some of which can pose zoonotic health concerns. Many conditions present with nonspecific clinical signs (lethargy, variable degrees of diarrhea, and for most sick rodents, presenting hunched with spiky fur), necessitating additional laboratory testing to reach a diagnosis. Primary tumors of the digestive tract are also presented as well as miscellaneous conditions ranging from toxins to trauma.


title: Efficacy and Safety of Integrated Traditional Chinese and Western Medicine for Corona Virus Disease 2019 (COVID-19): a systematic review and meta-analysis

text: COVID-19 has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as “Integrated Medicine”) to corona virus disease 2019 (COVID-19). We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses using the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, respectively, both of which were demonstrated in effect size and 95% confidence intervals. A total of 11 studies were included. Four were RCTs and seven were CCSs. The samples of including studies ranged from 18 to 100 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (such as Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate [RR = 1.230, 95%CI (1.113, 1.359), P = 0.000], cure rate [RR = 1.604, 95%CI (1.181, 2.177), P = 0.002], severity illness rate [RR = 0.350, 95%CI (0.154, 0.792), P = 0.012], and hospital stay [WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002] of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients’ fever, and fatigue time (P < 0.05). This review found that Integrated Medicine had better effects and fewer adverse drug reactions for COVID-19. More high-quality RCTs will be needed in the future.


title: Impact of building ventilation systems and habitual indoor incense burning on SARS-CoV-2 virus transmissions in Middle Eastern countries

text: Abstract Majority of countries across the globe have employed improving building ventilation, quarantine, social distancing, and disinfections as a general measure of preventing SARS-CoV-2 virus transmissions. However, arid Middle Eastern countries with hot climate (elevated outdoor temperature and humidity levels) are experiencing a different situation. Unfortunately, these harsh ambient climatic conditions in Middle Eastern countries make it impossible for most buildings to utilize natural/mechanical ventilation systems. Besides, indoor air temperatures of most buildings are very low due to overconsumption of air conditioning, thereby, it can be a potential factor of virus spread in most residential homes and public buildings. Most importantly, habitual indoor burning of incense which is the major source of coarse (PM10; aerodynamic diameter <10 μm) and fine (PM2.5; aerodynamic diameter <2.5 μm) particulate matters (PM) could facilitate the transmission of SARS-CoV-2 virus droplets and particles in indoor environments. In fact, it increases the spread of the virus via inhalation in these countries, especially where the wearing of masks is not regulated in public, commercial and residential buildings. It is therefore highly recommended for the relevant public health agencies to critically assess the role of poor indoor environmental conditions including the burning of incense on virus transmissions, which may help to develop control measures for the future viral outbreak effectively.


title: Emergence of a group 3 coronavirus through recombination

text: Abstract Analyses of turkey coronavirus (TCoV), an enteric disease virus that is highly similar to infectious bronchitis virus (IBV) an upper-respiratory tract disease virus in chickens, were conducted to determine the adaptive potential, and genetic changes associated with emergence of this group 3 coronavirus. Strains of TCoV that were pathogenic in poults and nonpathogenic in chickens did not adapt to cause disease in chickens. Comparative genomics revealed two recombination sites that replaced the spike gene in IBV with an unidentified sequence likely from another coronavirus, resulting in cross-species transmission and a pathogenicity shift. Following emergence in turkeys, TCoV diverged to different serotypes through the accumulation of mutations within spike. This is the first evidence that recombination can directly lead to the emergence of new coronaviruses and new coronaviral diseases, emphasizing the importance of limiting exposure to reservoirs of coronaviruses that can serve as a source of genetic material for emerging viruses.


title: Analytical performance of the Alere™ i Influenza A&B assay for the rapid detection of influenza viruses

text: The analytical performance of the new Alere™ i Influenza A&B kit (AL-Flu) assay, based on isothermal nucleic acids amplification, was evaluated and compared with an antigen detection method, SD Bioline Influenza Virus Antigen Test (SDB), and an automated real-time RT-PCR, Simplexa™ Flu A/B & VRS Direct assay (SPX), for detection of influenza viruses. An “in-house” RT-PCR was used as the reference method. Sensitivity of AL-Flu, SDB, and SPX was 71.7%, 34.8%, and 100%, respectively. Specificity was 100% for all techniques. The turnaround time was 13 min for AL-Flu, 15 min for SDB, and 75 min for SPX. The Alere™ i Influenza A&B assay is an optimal point-of-care assay for influenza diagnosis in clinical emergency settings, and is more sensitive and specific than antigen detection methods.


title: Identifying potential undocumented COVID-19 using publicly reported influenza-like-illness and laboratory-confirmed influenza disease in the United States: An approach to syndromic surveillance?

text: In the absence of widespread testing, syndromic surveillance approaches may be useful for understanding potential undocumented COVID-19 in the United States. We used publicly available data from the Centers for Disease Control and Prevention FluView Interactive to evaluate its potential for COVID-19 syndromic surveillance. Unlike the prior three influenza seasons, we found a 76% decrease in influenza positive tests and a 27% increase in influenza like illness during the weeks since COVID-19 outbreaks began in the United States, which suggests FluView's potential utility for COVID-19 syndromic surveillance.


title: Antiviral activities of mycophenolic acid and IMD‐0354 against SARS‐CoV‐2

text: In this study, anti‐SARS‐CoV‐2 activity of mycophenolic acid (MPA) and IMD‐0354 was analyzed, these compounds were chosen based on their antiviral activities against other coronaviruses. Since they also inhibit Dengue virus (DENV) infection, other anti‐DENV compounds/drugs were also assessed. Using SARS‐CoV‐2‐infected VeroE6/TMPRSS2 cells, MPA and IMD‐0354, but not other anti‐DENV compounds/drugs, showed significant anti‐SARS‐CoV‐2 activity. Although MPA reduced the viral RNA level by only ~100‐fold, its EC(50) was as low as 0.87µM, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets coronaviral papain‐like protease and its study would be useful in the development of novel anti‐SARS‐CoV‐2 drugs. This article is protected by copyright. All rights reserved.


title: Could injured skin be a reservoir for SARS-COV2 virus spread?

text: Abstract The current corona virus disease 2019 (COVID-19) outbreak which is caused by SARS-COV2 is still expanding. The authors tried to focus a spotlight on the injured skin as a reservoir of SARS-COV2 to decrease the infection rate.


title: Estimating Absolute and Relative Case Fatality Ratios from Infectious Disease Surveillance Data

text: Knowing which populations are most at risk for severe outcomes from an emerging infectious disease is crucial in deciding the optimal allocation of resources during an outbreak response. The case fatality ratio (CFR) is the fraction of cases that die after contracting a disease. The relative CFR is the factor by which the case fatality in one group is greater or less than that in a second group. Incomplete reporting of the number of infected individuals, both recovered and dead, can lead to biased estimates of the CFR. We define conditions under which the CFR and the relative CFR are identifiable. Furthermore, we propose an estimator for the relative CFR that controls for time-varying reporting rates. We generalize our methods to account for elapsed time between infection and death. To demonstrate the new methodology, we use data from the 1918 influenza pandemic to estimate relative CFRs between counties in Maryland. A simulation study evaluates the performance of the methods in outbreak scenarios. An R software package makes the methods and data presented here freely available. Our work highlights the limitations and challenges associated with estimating absolute and relative CFRs in practice. However, in certain situations, the methods presented here can help identify vulnerable subpopulations early in an outbreak of an emerging pathogen such as pandemic influenza.


title: Aminopeptidase N is a major receptor for the enteropathogenic coronavirus TGEV

text: CORONAVIRUSES, like many animal viruses, are characterized by a restricted host range and tissue tropism(1). Transmissible gastroenteritis virus (TGEV), a major pathogen causing a fatal diarrhoea in newborn pig, replicates selectively in the differentiated enterocytes covering the villi of the small intestine(2). To investigate the molecular determinants of the infection, we characterized the surface molecule used by the virus for binding and entry into host cells. Here we report that aminopeptidase N, an ectoenzyme abundantly expressed at the apical membrane of the enterocytes, serves as a receptor for TGEV. Monoclonal antibodies were selected for their ability to block infection by TGEV of porcine cell lines. They recognized a brush-border membrane protein of M(r), 150K, which was identified as aminopeptidase N by ammo-terminal sequencing. Two lines of evidence supported the view that the peptidase itself acts as a receptor. First, virions bound specifically to aminopep-tidase N that was purified to homogeneity. Second, recombinant expression of aminopeptidase N conferred infectivity by TGEV to an otherwise non-permissive cell line.


Impact of small-N studies during a pandemic


System-wide health-care shocks and regulatory interventions in the face of the emergency: are there some lessons to be learned from the COVID-19 crisis?


title: Peritoneal Macrophages of Pathogen‐Free Rats but not of Conventional Rats Secrete Elastolytic Activity

text: Elicited peritoneal macrophages from Sprague‐Dawley rats conventionally bred and housed failed, as we have reported, to produce detectable elastolytic activity in culture. They did produce lysozyme and plasminogen activator. We now show that in contrast to these cells, macrophages from pathogen‐free, barrier‐sustained rats produced readily demonstrable elastolytic activity. Rats raised pathogen‐free and subsequently housed conventionally for 2–4 wk appeared to lose the capacity to afford macrophages producing elastase. At the same time they acquired infections with several rat pathogens including Spironucleus muris, Kilham rat virus, sialodacryoadinitis virus, and mycoplasma pulmonis. The acquisition by the rats of one or more of these infections, conditions conducive to infection, or both factors may have suppressed their capacity to yield elastolytic activity.


title: COVID-19 in Italy: considerations on official data

text: Abstract COVID-19 represents a major public health issue in Italy; estimating the size of the outbreak could direct public health policies and inform us on the extent of the reorganization needed in the healthcare system, on the efficacy of quarantine measures and eventually on the achievement of herd immunity. In order to chart the real extent of COVID-19 infection in Italy, official data need to be interpreted considering various aspects such the “suspected-case” definition, that changed during the past months, the management of asymptomatic and untested symptomatic cases, the deaths reporting system and short-term fluctuations. All these aspects should be taken into consideration when reflecting about the meaning of the official COVID-19 figures in Italy. Regionalization of the healthcare system and fragmentation of data represent real challenges in the management of the COVID-19 outbreak in Italy. Authors’ opinion is that a transparent and accurate reporting could guide policymaking and help reorganize health services.


title: Pseudorabies virus induces apoptosis in tissue culture cells

text: The process of cell death as a result of exposure to pseudorabies virus (PRV) in cultured cells was examined and specific features characteristic of apoptosis were observed. At early times of infection, externalization of membrane phospholipid phophatidylserine was detected by flow cytometry analysis. During the infection process, caspase 3-like protease activity was induced and the activity increased in a time dependent manner. Cellular DNA degradation was demonstrated by agarose gel electrophoresis. Morphologic changes of the nucleus that included chromatin condensation and margination to the periphery of the nucleus were evident in electron microscopy analysis. These biochemical and morphologic changes demonstrated that, during PRV replication, the host cell was induced to undergo apoptosis.


title: Changes in mRNA abundance drive shuttling of RNA binding proteins, linking cytoplasmic RNA degradation to transcription

text: Alterations in global mRNA decay broadly impact multiple stages of gene expression, although signals that connect these processes are incompletely defined. Here, we used tandem mass tag labeling coupled with mass spectrometry to reveal that changing the mRNA decay landscape, as frequently occurs during viral infection, results in subcellular redistribution of RNA binding proteins (RBPs) in human cells. Accelerating Xrn1-dependent mRNA decay through expression of a gammaherpesviral endonuclease drove nuclear translocation of many RBPs, including poly(A) tail-associated proteins. Conversely, cells lacking Xrn1 exhibited changes in the localization or abundance of numerous factors linked to mRNA turnover. Using these data, we uncovered a new role for relocalized cytoplasmic poly(A) binding protein in repressing recruitment of TATA binding protein and RNA polymerase II to promoters. Collectively, our results show that changes in cytoplasmic mRNA decay can directly impact protein localization, providing a mechanism to connect seemingly distal stages of gene expression.


title: Pneumonia and Streptococcus pneumoniae vaccine

text: Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other microorganisms. Streptococcus pneumoniae, a gram-positive bacterium with over 90 serotypes, is the most common causative agent. Moreover, comorbid factors including heart failure, renal disease, and pulmonary disease could increase the risk of pneumococcal pneumonia. Since the advent of the pneumococcal vaccine in the 1980s, the incidence of pneumonia has decreased significantly. However, current vaccines confer only limited protection against serotypes included in the vaccine. Thus, to overcome this limitation, new types of pneumococcal vaccines have been sought and under clinical trials. In this review, we discuss pneumonia and summarize the various types of pneumococcal vaccines in progress.


Loneliness at epidemic levels in America


title: Clinical and Epidemiologic Characteristics of 3 Early Cases of Influenza A Pandemic (H1N1) 2009 Virus Infection, People’s Republic of China, 2009

text: On May 7, 2009, a national network was organized in the People’s Republic of China for the surveillance, reporting, diagnosis, and treatment of influenza A pandemic (H1N1) 2009 virus infection (pandemic [H1N1] 2009). Persons with suspected cases are required to report to the Chinese Center for Disease Control and Prevention and the Ministry of Health within 24 hours; the patient’s close contacts are then traced and placed in quarantine for 7 days. We report 3 confirmed early cases of pandemic (H1N1) 2009. Two cases were imported from United States; the other was imported from Canada. The patients exhibited fever and signs and other symptoms that were indistinguishable from those of seasonal influenza. Serial virologic monitoring of pharyngeal swabs showed that they were negative for pandemic (H1N1) 2009 virus by real-time reverse transcription–PCR 4–6 days after onset of illness. One close contact whose sample tested positive for pandemic (H1N1) 2009 virus had no symptoms during quarantine. A national network is essential for controlling pandemic (H1N1) 2009.


title: Chapter 9 Nutritional Care of the Child with Human Immunodeficiency Virus Infection in the United States A Historical and Contemporary Perspective

text: In well-resourced settings, early infant diagnosis and administration of life-saving antiretrovirals (ARVs) have significantly improved clinical outcomes in pediatric human immunodeficiency virus (HIV) infection. The dramatic increase in survival rates is associated with enhancements in overall quality of life, which reflect a multidisciplinary, holistic approach to care. Current optimism starkly contrasts with the outlook and prognosis two decades ago, when failure to thrive and wasting syndrome from uncontrolled pediatric HIV infection resulted from poor oral intake, malabsorption, chronic diarrhea, and a persistently catabolic state. The tenets of care developed from that era still hold true in that all infants, children, and adolescents with HIV require comprehensive nutritional services in addition to effective combination antiretroviral therapy (cART). This chapter will review the principles of nutrition in the pre- and post-cART eras and discuss the etiologic factors associated with malnutrition, with an emphasis on interventions that have favorably impacted the growth and body composition of infants, children and adolescents with HIV.


title: The development of a multiplex real-time PCR for the detection of herpes simplex virus 1 and 2, varizella zoster virus, adenovirus and Chlamydia trachomatis from eye swabs

text: Abstract Infectious conjunctivitis can be difficult to distinguish clinically due to the considerable overlap in clinical presentation so clinical diagnosis of conjunctivitis is often insufficient. It is therefore necessary to have a rapid diagnostic test that differentiates between the different causes of infectious conjunctivitis. Screening clinical samples by sample type/syndrome based multiplex real time PCR would allow for rapid detection of a variety of pathogens simultaneously, which will in turn aid in the treatment and clinical management of the patient. A multiplex real-time PCR assay for rapid and simultaneous detection of HSV 1 and 2, VZV, adenovirus and Chlamydia trachomatis (C. trachomatis) from eye swabs was developed and evaluated. The multiplex assay was shown to be sensitive, specific and robust. Reductions in sample turn around times have been achieved by reducing the amount of separate tests needed to be carried out.


title: CD4–CD8-T cells contribute to the persistence of viral hepatitis by striking a delicate balance in immune modulation

text: Abstract Viral hepatitis remains the most common cause of liver disease and a major public health problem. Here, we focus on the role of CD4 CD8 double negative T (DN T) cells involved in the mechanisms of viral persistence in hepatitis. C3H/HeJ mice infected with murine hepatitis virus strain 3 (MHV-3) were used to display chronic viral hepatitis. DN T cells dramatically increased in MHV-3 infected mice. Adoptive transfer of DN T cells from MHV-3 infected mice led to a significant increase in mice survival. The DN T cells with production of IFN-γ and IL-2 are able to kill virus-specific CD8+ T cells via the Fas/FasL dependent pathway. The delicate balance of multiple effects of DN T cells may lead to viral persistence in MHV-3 induced hepatitis. In short, our study identified DN T cells contributing to viral persistence in MHV-3 induced hepatitis in C3H/HeJ mice, which provides a rationale for modulating DN T cells for the management of viral hepatitis.


title: Genomic analysis of emerging pathogens: methods, application and future trends

text: The number of emerging infectious diseases is increasing. Characterizing novel or re-emerging infections is aided by the availability of pathogen genomes. In this review, we evaluate methods that exploit pathogen sequences and the contribution of genomic analysis to understand the epidemiology of recently emerged infectious diseases.


docid: eniovfwy

title: Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine

text: Abstract Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry.


title: SARS‐CoV‐2 and Guillain‐Barré syndrome: AIDP variant with favorable outcome

text: The entire world has been experiencing the outbreak of a novel infectious agent known as severe acute respiratory syndrome corona virus 2 (SARS‐CoV‐2), which is responsible for the coronavirus disease 19 (COVID‐19)(1). Life‐threatening complications described in SARS‐CoV‐2 infected patients include acute respiratory distress syndrome, acute kidney failure and cardiac injury(2). Nonetheless, only few neurological complications have been described so far(3).


title: Influenza in Africa

text: Maria Yazdanbakhsh and Peter Kremsner argue that there needs to be better awareness, surveillance, and clinical management of common febrile diseases in Africa, especially influenza.


Low prevalence of arrhythmias in clinically stable COVID‐19 patients


title: Ruxolitinib for tocilizumab‐refractory severe COVID‐19 infection

text: Whilst the majority of patients with COVID‐19 infection have mild self‐limiting symptoms, for some the SARS‐CoV2 virus can trigger a severe hyperinflammatory syndrome which is life threatening. Anti‐IL6 therapy has shown promise in restraining the hyperinflammatory syndrome and while IL‐6 is a pleiotropic mediatory of the inflammatory response, redundancy within inflammatory pathways means that the use of such targeted monoclonal therapy may have too restricted a repertoire in some patients. We present the case of a 53‐year‐old haematopoetic stem cell transplant recipient who developed a severe COVID‐19 that was refractory to anti‐IL6 therapy, but responded to Jak‐Stat inhibition with ruxolitinib, demonstrating its safety and efficacy in this setting.


title: Viral and atypical respiratory co‐infections in COVID‐19: a systematic review and meta‐analysis

text: OBJECTIVES: Respiratory co‐infections have the potential to affect the diagnosis and treatment of COVID‐19 patients. This meta‐analysis was performed to analyze the prevalence of respiratory pathogens (viruses and atypical bacteria) in COVID‐19 patients. METHODS: This review was consistent with Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA). Searched databases included: PubMed, EMBASE, Web of Science, Google Scholar, and grey literature. Studies with a series of SARS‐CoV‐2‐positive patients with additional respiratory pathogen testing were included. Independently, 2 authors extracted data and assessed quality of evidence across all studies using Cochrane's Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology and within each study using the Newcastle Ottawa scale. Data extraction and quality assessment disagreements were settled by a third author. Pooled prevalence of co‐infections was calculated using a random‐effects model with univariate meta‐regression performed to assess the effect of study subsets on heterogeneity. Publication bias was evaluated using funnel plot inspection, Begg's correlation, and Egger's test. RESULTS: Eighteen retrospective cohorts and 1 prospective study were included. Pooling of data (1880 subjects) showed an 11.6% (95% confidence interval [CI] = 6.9–17.4, I (2) = 0.92) pooled prevalence of respiratory co‐pathogens. Studies with 100% co‐pathogen testing (1210 subjects) found a pooled prevalence of 16.8% (95% CI = 8.1–27.9, I (2) = 0.95) and studies using serum antibody tests (488 subjects) found a pooled prevalence of 26.8% (95%, CI = 7.9–51.9, I (2) = 0.97). Meta‐regression found no moderators affecting heterogeneity. CONCLUSION: Co‐infection with respiratory pathogens is a common and potentially important occurrence in patients with COVID‐19. Knowledge of the prevalence and type of co‐infections may have diagnostic and management implications.


title: Biting back against rabies

text: World Rabies Day, on 28 September, focuses our attention on a horrific, preventable disease that still kills tens of thousands of people each year.


COVID-19 & Antiepileptic Drugs: Should We Pay Attention?


title: Human genome research in China

text: Significant progress in human genome research has been made in China since 1994. This review aims to give a brief and incomplete introduction to the major research institutions and their achievements in human genome sequencing and functional genomics in medicine, with emphasis on the “1% Sequencing Project”, the generation of single nucleotide polymorphism and haplotype maps of the human genome, disease gene identification, and the molecular characterization of leukemia and other diseases. Chinese efforts towards the sequencing of pathogenic microbial genomes and of the rice (Oryza sativa ssp. Indica) genome are also described.


Future vaccines for a globalized world


title: Bacillus Calmette–Guérin vaccine, age and gender relation to COVID-19 spread and mortality

text: Abstract COVID-19 is affecting different countries all over the world with great variation in infection rate and death ratio. Some reports suggested a relation between the Bacillus Calmette-Guérin (BCG) vaccine and the malaria treatment to the prevention of SARS-CoV-2 infection. Some reports related infant's lower susceptibility to the BCG vaccine. Some other reports a higher risk in males compared to females in such COVID-19 pandemic. Also, some other reports claimed the possible use of chloroquine and hydroxychloroquine as prophylactic in such a pandemic. The present commentary is to discuss the possible relation between those factors and SARS-CoV-2 infection.


title: Comprehensive detection of causative pathogens using real-time PCR to diagnose pediatric community-acquired pneumonia

text: Abstract We have developed a real-time reverse transcription-PCR (RT-PCR) method to detect 13 respiratory viruses: influenza virus A and B; respiratory syncytial virus (RSV) subgroup A and B; parainfluenza virus (PIV) 1, 2, and 3; adenovirus; rhinovirus (RV); enterovirus; coronavirus (OC43); human metapneumovirus (hMPV); and human bocavirus (HBoV). The new method for detection of these viruses was applied simultaneously with real-time PCR for the detection of six bacterial pathogens in clinical samples from 1700 pediatric patients with community-acquired pneumonia (CAP). Of all the patients, 32.5% were suspected to have single bacterial infections; 1.9%, multiple bacterial infections; 15.2%, coinfections of bacteria and viruses; 25.8%, single viral infections; and 2.1%, multiple viral infections. In the remaining 22.6%, the etiology was unknown. The breakdown of suspected causative pathogens was as follows: 24.4% were Streptococcus pneumoniae, 14.8% were Mycoplasma pneumoniae, 11.3% were Haemophilus influenzae, and 1.4% were Chlamydophila pneumoniae. The breakdown of viruses was as follows: 14.5% were RV, 9.4% were RSV, 7.4% were hMPV, 7.2% were PIV, and 2.9% were HBoV. The new method will contribute to advances in the accuracy of diagnosis and should also result in the appropriate use of antimicrobials.


title: Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms

text: OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m(6)A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.


Epidemiological research priorities for public health control of the ongoing global novel coronavirus (2019-nCoV) outbreak


Acute At Home Management of Anaphylaxis During The Covid-19 Pandemic


Investigation of COVID-19 cases and use of serological tests


CLUE: COVID‐19 Lung Ultrasound in Emergency Department.


title: SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner

text: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octasaccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with higher affinity to heparin (KD 55 nM) compared to the receptor binding domain (RBD, KD 1 µM) alone. An octasaccharide composed of IdoA2S-GlcNS6S could inhibit spike-heparin interaction with an IC50 of 38 nM. Our data supports a model in which the RBD of the spike of SARS-CoV-2 confers sequence specificity for HS expressed by target cells whereas an additional HS binding site in the S1/S2 proteolytic cleavage site enhances the avidity of binding. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.


title: Emergency Department Management of the COVID-19 Pandemic

text: Abstract Background Emergency Departments (EDs) need to be prepared to manage crises and disasters in both the short and long term. The COVID-19 pandemic has necessitated a rapid overhaul of several aspects of ED operations in preparation for a sustained response. Objective of the Review:We present the management of the COVID-19 crisis in three EDs (one large academic site, and two community sites) within the same health system. Discussion Aspects of ED throughput, including patient screening, patient room placement, and disposition are reviewed, along with departmental communication procedures and staffing models. Visitor policies are additionally discussed. Special considerations are given to airway management and the care of psychiatric patients. Brief guidance around the use of personal protective equipment is also included. Conclusions A crisis like the COVID-19 pandemic requires careful planning to facilitate urgent restructuring of many aspects of an ED. By sharing our departments’ responses to the COVID-19 pandemic, we hope other departments can better prepare for this crisis and the next.


title: Mechanisms of viral emergence

text: A number of virologic and environmental factors are involved in the emergence and re-emergence of viral disease. Viruses do not conservatively occupy a single and permanent ecological niche. Rather, due to their intrinsic capacity for genetic change, and to the evolvability of fitness levels, viruses display a potential to parasitize alternative host species. Mutation, recombination and genome segment reassortment, and combination of these molecular events, produce complex and phenotypically diverse populations of viruses, which constitute the raw material on which selection acts. The majority of emerging viral diseases of humans have a zoonotic origin. Sociologic and ecologic factors produce diverse and changing environments in which viral subpopulations have ample opportunities to be selected from intrinsically heterogeneous viral populations, particularly in the case of RNA viruses. In this manner, new human, animal and plant viruses have emerged periodically and, from all evidence, will continue to emerge. This article reviews some of the mechanisms that have been identified in viral emergence, with a focus on the importance of genetic variation of viruses, and on the general concept of biological complexity.


title: Assessing resilience of healthcare infrastructure exposed to COVID-19: emerging risks, resilience indicators, interdependencies and international standards

text: In the moment of preparation of this paper, the world is still globally in grip of the Corona (COVID-19) crisis, and the need to understand the broader overall framework of the crisis increases. As in similar cases in the past, also with this one, the main interest is on the “first response”. Fully appreciating the efforts of those risking their lives facing pandemics, this paper tries to identify the main elements of the larger, possibly global, framework, supported by international standards, needed to deal with new (emerging) risks resulting from threats like Corona and assess the resilience of systems affected. The paper proposes that future solutions should include a number of new elements, related to both risk and resilience. That should include broadening the scope of attention, currently focused onto preparation and response phases, to the phases of “understanding risks”, including emerging risks, and transformation and adaptation. The paper suggests to use resilience indicators in this process. The proposed approach has been applied in different cases involving critical infrastructures in Europe (energy supply, water supply, transportation, etc., exposed to various threats), including the health system in Austria. The detailed, indicator-based, resilience analysis included mapping resilience, resilience stress-testing, visualization, etc., showing, already before the COVID-19, the resilience (stress-testing) limits of the infrastructures. A simpler (57 indicator based) analysis has, then been done for 11 countries (including Austria). The paper links these results with the options available in the area of policies, standards, guidelines and tools (such as the RiskRadar), with focus on interdependencies and global standards—especially the new ISO 31,050, linking emerging risks and resilience.


title: Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2

text: Abstract A DNA vaccine against infectious bronchitis virus (IBV) can induce specific humoral and cell-mediated immunity. However, compared to conventional vaccines, DNA vaccines usually induce poor antibody responses. To develop a more potent IBV DNA vaccine formulations, a monocistronic vector encoding the nucleocapsid protein of IBV and a bicistronic vector separately encoding the nucleocapsid protein and immune-stimulatory interleukin-2 were constructed. When the DNA vaccines were administered to the quadriceps muscle of chickens, the induced humoral and cellular responses were evaluated. There was a significant difference in ELISA antibody levels elicited by either monocistronic or bicistronic DNA vaccines. The percentage of CD3+, CD3+CD8+ and CD3+CD4+ subgroups of peripheral blood T-lymphocytes in chickens immunized with bicistronic DNA vaccine were higher than those in chickens immunized with monocistronic DNA vaccine. When chickens were challenged with a virulent strain of IBV, the protective efficacy could be enhanced significantly after immunization with bicistronic DNA vaccine. These results demonstrated that bicistronic DNA vaccine is an effective approach to increase IBV DNA vaccine immunogenicity.


title: Coronavirus Disease 2019 (COVID-19): Protecting Hospitals From the Invisible

text: Coronavirus disease 2019 (COVID-19) is optimized to spread widely: Its signs and symptoms are largely indistinguishable from those of other respiratory viruses. This commentary specifically addresses best ways to protect our hospitals against COVID-19.


title: Teledentistry during COVID-19 pandemic

text: BACKGROUND AND AIMS: Dentistry involve close face-to-face interaction with patients, hence during the COVID-19 pandemic, it has mostly been suspended. Teledentistry can offer an innovative solution to resume dental practice during this pandemic. In this review, we provide a brief overview of applications of teledentistry. METHODS: Articles on teledentistry, relevant to this review, were searched and consulted from PubMed, Google Scholar, and Cochrane database. RESULTS: Teledentistry is the remote facilitating of treatment, guidance, and education via the use of information technology instead of direct face-to-face contact with patients. Teleconsultation, telediagnosis, teletriage, and telemonitoring are subunits of teledentistry that have important functions relevant to dental patients. There are many challenges for acceptance of teledentistry by the dentists as well as patients, which need to be addressed urgently. CONCLUSION: Teledentistry can offer a novel solution to resume dental practice during the current pandemic, hence, the need of the hour is to incorporate teledentistry into routine dental practice. If not fully replace, at least teledentistry can complement the existing compromised dental system during the current pandemic.


title: The Cytokine and Chemokine Profiles in Patients with Hand, Foot and Mouth Disease of Different Severities in Shanghai, China, 2010

text: BACKGROUND AND PURPOSE: Systemic upregulation of inflammatory cytokines is characteristic of critical severe hand, foot, and mouth disease (HFMD) with pulmonary edema. Thus, immunomodulatory medicines such as steroids, including methylprednisolone, have been proposed to treat patients with severe HFMD in China, because it is postulated that inflammatory cytokines play a role in the development of severe complications. This study is to further investigate the inflammatory response in the relatively mild HFMD patients, and whether steroid treatment has a beneficial effect on the suppression of inflammation in HFMD patients. METHOD: We measured the levels of 50 kinds of chemokines, cytokines, growth factors and soluble receptors in serum samples from control patients without HFMD and the HFMD patients with or without prior treatment of intravenous methylprednisolone. RESULTS: Our present study found that even relatively mild HFMD patients without central nervous system (CNS) complications had elevated serum levels of inflammatory cytokines, including interleukin (IL)-3, IL-6, IL-12p40, and tumor necrosis factor (TNF)-α, which suggested systemic inflammation. In contrast, these patients also have decreased levels of other serum biomarkers, including IL-1Ra, IL-8, IL-16, soluble ICAM-1, CXCL-1, and CCL27. The dysregulation of cytokine and chemokine expression may be involved in CNS complications and unbalanced circulating leukocytes in HFMD patients. Surprisingly, patients treated with methylprednisolone had no difference in the expression levels of HFMD-associated biomarkers instead had slightly increased levels of IL-17A, which was not associated with the occurrence of HFMD. CONCLUSION: Whether steroid treatment has any beneficial effect on the prognosis of HFMD patients requires to be further investigated.


COVID-19 guidance in chronic diseases: a need to reach across the borders of the traditional medical specialities


title: Chapter 15 Lymphadenopathy and Splenomegaly

text: Summary This chapter provides an approach to the diagnosis, causes and clinical investigation of lymphadenopathy and splenomegaly.


title: Homologous genetic recombination in the yellow head complex of nidoviruses infecting Penaeus monodon shrimp

text: Abstract Yellow head virus (YHV) is a highly virulent pathogen of Penaeus monodon shrimp. It is one of six known genotypes in the yellow head complex of nidoviruses which also includes mildly pathogenic gill-associated virus (GAV, genotype 2) and four other genotypes (genotypes 3–6) that have been detected only in healthy shrimp. In this study, comparative phylogenetic analyses conducted on replicase- (ORF1b) and glycoprotein- (ORF3) gene amplicons identified 10 putative natural recombinants amongst 28 viruses representing all six genotypes from across the Indo-Pacific region. The ∼4.6 kb genomic region spanning the two amplicons was sequenced for three putative recombinant viruses from Vietnam (genotype 3/5), the Philippines (genotype 5/2) and Indonesia (genotype 3/2). SimPlot analysis using these and representative parental virus sequences confirmed that each was a recombinant genotype and identified a recombination hotspot in a region just upstream of the ORF1b C-terminus. Maximum-likelihood breakpoint analysis predicted identical crossover positions in the Vietnamese and Indonesian recombinants, and a crossover position 12 nt upstream in the Philippine recombinant. Homologous genetic recombination in the same genome region was also demonstrated in recombinants generated experimentally in shrimp co-infected with YHV and GAV. The high frequency with which natural recombinants were identified indicates that genetic exchange amongst genotypes is occurring commonly in Asia and playing a significant role in expanding the genetic diversity in the yellow head complex. This is the first evidence of genetic recombination in viruses infecting crustaceans and has significant implications for the pathogenesis of infection and diagnosis of these newly emerging invertebrate pathogens.


title: Management of Tracheostomy during COVID-19 Outbreak: Heat and Moisture Exchanger Filter and Closed Suctioning System

text: • Precautions for safer management of tracheostomy should be taken for all patients. • HMEFs and closed endotracheal suctioning systems protect patients and healthcare professionals. • Precaution for reduce the COVID-19 diffusion should be taken until the epidemic is controlled.


title: Chapter 42 Probiotics and Prebiotics for Prevention of Viral Respiratory Tract Infections

text: Abstract This chapter introduces the importance of viral upper respiratory tract infections and evidence that probiotics, prebiotics, and synbiotics may reduce not only their incidence, but also their duration and severity. It starts by explaining the importance of viral respiratory infections and the common cold including their prevalence, morbidity, mortality, and cost. The mechanisms of action are discussed next. Later, it represents the clinical trials using probiotics and prebiotics for the prevention of viral infection in different age groups. At the end of the chapter, a summary of latest evidences is presented.


title: Western European epidemiological survey for parvovirus and coronavirus infections in dogs

text: Abstract An epidemiological survey for canine parvovirus (CPV) and canine coronavirus (CCoV) infections was conducted in Western Europe. A total of 156 faecal samples were collected from dogs with diarrhoea in Spain (n= 47), Italy (n =39), France (n =26), Germany (n =21), the United Kingdom (n =8), Belgium (n =10), and the Netherlands (n =5). Using molecular assays for virus detection and characterisation, CPV and CCoV were found to be widespread in European dog populations, either alone or in mixed infections. In agreement with previous reports, the original type CPV-2 was shown not to circulate in European dogs. The recently identified virus variant CPV-2c was predominant in Italy and Germany and present at high rates in Spain and France but was not detected in the UK or Belgium. Except for the UK, CCoV genotype I was identified in all European countries involved in the survey, albeit at a lower prevalence rates than CCoV genotype II.


title: The coronavirus macrodomain is required to prevent PARP-mediated inhibition of virus replication and enhancement of IFN expression

text: ADP-ribosylation is a ubiquitous post-translational addition of either monomers or polymers of ADP-ribose to target proteins by ADP-ribosyltransferases, usually by interferon-inducible diphtheria toxin-like enzymes known as PARPs. While several PARPs have known antiviral activities, these activities are mostly independent of ADP-ribosylation. Consequently, less is known about the antiviral effects of ADP-ribosylation. Several viral families, including Coronaviridae, Togaviridae, and Hepeviridae, encode for macrodomain proteins that bind to and hydrolyze ADP-ribose from proteins and are critical for optimal replication and virulence. These results suggest that macrodomains counter cellular ADP-ribosylation, but whether PARPs or, alternatively, other ADP-ribosyltransferases cause this modification is not clear. Here we show that pan-PARP inhibition enhanced replication and inhibited interferon production in primary macrophages infected with macrodomain-mutant but not wild-type coronavirus. Specifically, knockdown of two abundantly expressed PARPs, PARP12 and PARP14, led to increased replication of mutant but did not significantly affect wild-type virus. PARP14 was also important for the induction of interferon in mouse and human cells, indicating a critical role for this PARP in the regulation of innate immunity. In summary, these data demonstrate that the macrodomain is required to prevent PARP-mediated inhibition of coronavirus replication and enhancement of interferon production.


Precautions in ophthalmic practice in a hospital with a major acute SARS outbreak: an experience from Hong Kong


title: The predictors of 3- and 30-day mortality in 660 MERS-CoV patients

text: BACKGROUND: The mortality rate of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) patients is a major challenge in all healthcare systems worldwide. Because the MERS-CoV risk-standardized mortality rates are currently unavailable in the literature, the author concentrated on developing a method to estimate the risk-standardized mortality rates using MERS-CoV 3- and 30-day mortality measures. METHODS: MERS-CoV data in Saudi Arabia is publicly reported and made available through the Saudi Ministry of Health (SMOH) website. The author studied 660 MERS-CoV patients who were reported by the SMOH between December 2, 2014 and November 12, 2016. The data gathered contained basic demographic information (age, gender, and nationality), healthcare worker, source of infection, pre-existing illness, symptomatic, severity of illness, and regions in Saudi Arabia. The status and date of mortality were also reported. Cox-proportional hazard (CPH) models were applied to estimate the hazard ratios for the predictors of 3- and 30-day mortality. RESULTS: 3-day, 30-day, and overall mortality were found to be 13.8%, 28.3%, and 29.8%, respectively. According to CPH, multivariate predictors of 3-day mortality were elderly, non-healthcare workers, illness severity, and hospital-acquired infections (adjusted hazard ratio (aHR) =1.7; 8.8; 6.5; and 2.8, respectively). Multivariate predictors of 30-day mortality were elderly, non-healthcare workers, pre-existing illness, severity of illness, and hospital-acquired infections (aHR =1.7; 19.2; 2.1; 3.7; and 2.9, respectively). CONCLUSIONS: Several factors were identified that could influence mortality outcomes at 3 days and 30 days, including age (elderly), non-healthcare workers, severity of illness, and hospital-acquired infections. The findings can serve as a guide for healthcare practitioners by appropriately identifying and managing potential patients at high risk of death.


title: Inhibition of aminopeptidases N, A and W A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme

text: Abstract The effects of a range of metallopeptidase inhibitors on the activities of the porcine kidney cell surface zinc aminopeptidases, aminopeptidase A (AP-A; EC 3.4.11.2), aminopeptidase N (AP-N; EC 3.4.11.7) and aminopeptidase W (AP-W; EC 3.4.11.16), have been directly compared. Amastatin and probestin were effective against all three aminopeptidases, with the concentration of inhibitor required to cause 50% inhibition (I50) in the low micromolar range (I50 = 1.5–20 μM), except for probestin with AP-N which displayed an I50 of 50 nM. Actinonin failed to inhibit significantly either AP-A or AP-W, and thus can be considered a relatively selective inhibitor (I50 = 2.0 μM of AP-N. In contrast, bestatin was a relatively poor inhibitor of AP-N (I50 = 89 μm) and failed to inhibit AP-A, but was more potent towards AP-W (I50 = 7.9 μM). Thus, some of the observed chemotherapeutic actions of bestatin may be due to inhibition of cell-surface AP-W. A number of other metallopeptidase inhibitors, including inhibitors of endopeptidase-24.11 (EC 3.4.24.11) and membrane dipeptidase (EC 3.4.13.11), and the carboxylalkyl and phosphoryl inhibitors of angiotensin converting enzyme (EC 3.4.15.1) failed to inhibit significantly AP-A, AP-N or AP-W. However, AP-W was inhibited with I50 values in the micromolar range by the sulphydryl converting enzyme inhibitors rentiapril (I50 = 1.6 μM), zofenoprilat (I50 = 7.0 μM) and YS 980 (I50 = 17.7 μM). Neither AP-A nor AP-N were affected by these sulphydryl compounds. Inhibition of AP-W may account for some of the side effects noted with the clinical use of the sulphydryl converting enzyme inhibitors. The availability of compounds which are totally selective for AP-W over any of the other mammalian cell surface zinc aminopeptidases may aid in identifying endogenous substrates, and thus physiological or pathophysiological role(s) of AP-W.


title: Predictors of COVID-19 voluntary compliance behaviors: An international investigation

text: With a large international sample (n = 8317), the present study examined which beliefs and attitudes about COVID-19 predict 1) following government recommendations, 2) taking health precautions (including mask wearing, social distancing, handwashing, and staying at home), and 3) encouraging others to take health precautions. The results demonstrate the importance of believing that taking health precautions will be effective for avoiding COVID-19 and generally prioritizing one’s health. These beliefs continued to be important predictors of health behaviors after controlling for demographic and personality variables. In contrast, we found that perceiving oneself as vulnerable to COVID-19, the perceived severity of catching COVID-19, and trust in government were of relatively little importance. We also found that women were somewhat more likely to engage in these health behaviors than men, but that age was generally unrelated to voluntary compliance behaviors. These findings may suggest avenues and dead ends for behavioral interventions during COVID-19 and beyond.


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title: Challenges for mental health services during the 2020 COVID‐19 outbreak in Germany


title: Epidemiological and risk analysis of the H7N9 subtype influenza outbreak in China at its early stage

text: Dozens of human cases infected with H7N9 subtype avian influenza virus (AIV) have been confirmed in China since March, 2013. Distribution data of sexes, ages, professions and regions of the cases were analyzed in this report. The results showed that the elderly cases, especially the male elderly, were significantly more than expected, which is different from human cases of H5N1 avian influenza and human cases of the pandemic H1N1 influenza. The outbreak was rated as a Grade III (severe) outbreak, and it would evolve into a Grade IV (very severe) outbreak soon, using a method reported previously. The H7N9 AIV will probably circulate in humans, birds and pigs for years. Moreover, with the driving force of natural selection, the virus will probably evolve into highly pathogenic AIV in birds, and into a deadly pandemic influenza virus in humans. Therefore, the H7N9 outbreak has been assumed severe, and it is likely to become very or extremely severe in the future, highlighting the emergent need of forceful scientific measures to eliminate any infected animal flocks. We also described two possible mild scenarios of the future evolution of the outbreak.


title: COVID‐19: A threat to educated Muslim women's negotiated identity in Pakistan

text: This study attempts to explore how the lockdown/containment measures taken by the government during the COVID‐19 pandemic have threatened educated Muslim women's negotiated identity regarding wifehood and motherhood in urban Pakistan and how they struggle to reposition to reconstruct it. Through semi‐structured interviews, making an in‐depth comparative study of three differently situated cases (Muslim women), this study argues that the abnormal situation that has ensued from the pandemic has reinforced the vulnerability of women's nascent negotiated identity by landing them in a space where they are supposed by the normative structures to step back to carrying out their traditional responsibilities as ‘good’ wife and mother during the crisis. It has found that the pandemic has similarity in its impacts for the women in their familial lives, despite their being variously situated and resistive, due to the general religio‐culturally defined patriarchal social behaviour of the place (Pakistan) toward women and lack of action on the part of the state for implementing its laws of women's empowerment.


title: Effect of lockdown on the management of ischemic stroke: an Italian experience from a COVID hospital

text: OBJECTIVE: To evaluate the impact of the lockdown measures, consequent to the outbreak of COVID-19 pandemic, on the quality of pre-hospital and in-hospital care of patients with acute ischemic stroke. METHODS: This is an observational cohort study. Data sources were the clinical reports of patients admitted during the first month of lockdown and discharged with a confirmed diagnosis of stroke or TIA. Data were collected in the interval ranging from March 11th to April 11th 2020. As controls, we evaluated the clinical reports of patients with stroke or TIA admitted in the same period of 2019. RESULTS: The clinical reports of patients eligible for the study were 52 in 2020 (71.6 ± 12.2 years) and 41 in 2019 (73.7 ± 13.1 years). During the lockdown, we observed a significant increase in onset-to-door time (median = 387 vs 161 min, p = 0.001), a significant reduction of the total number of thrombolysis (7 vs 13, p = 0.033), a non-significant increase of thrombectomy (15 vs 9, p = 0.451), and a significant increase in door-to-groin time (median = 120 vs 93 min, p = 0.048). No relevant difference was observed between 2019 and 2020 in the total number of patients admitted. CONCLUSIONS: Due to the COVID-19 pandemic and lockdown measures, the stroke care pathway changed, involving both pre-hospital and in-hospital performances.


title: Development and Assessment of a Diagnostic DNA Oligonucleotide Microarray for Detection and Typing of Meningitis-Associated Bacterial Species

text: Meningitis is commonly caused by infection with a variety of bacterial or viral pathogens. Acute bacterial meningitis (ABM) can cause severe disease, which can progress rapidly to a critical life-threatening condition. Rapid diagnosis of ABM is critical, as this is most commonly associated with severe sequelae with associated high mortality and morbidity rates compared to viral meningitis, which is less severe and self-limiting. We have designed a microarray for detection and diagnosis of ABM. This has been validated using randomly amplified DNA targets (RADT), comparing buffers with or without formamide, in glass slide format or on the Alere ArrayTube(TM) (Alere Technologies GmbH) microarray platform. Pathogen-specific signals were observed using purified bacterial nucleic acids and to a lesser extent using patient cerebral spinal fluid (CSF) samples, with some technical issues observed using RADT and glass slides. Repurposing the array onto the Alere ArrayTube(TM) platform and using a targeted amplification system increased specific and reduced nonspecific hybridization signals using both pathogen nucleic and patient CSF DNA targets, better revealing pathogen-specific signals although sensitivity was still reduced in the latter. This diagnostic microarray is useful as a laboratory diagnostic tool for species and strain designation for ABM, rather than for primary diagnosis.


title: Epilepsy control during an epidemic: emerging approaches and a new management framework

text: Epidemics are a big threat to world health. The ongoing pandemic of corona virus disease 2019 (COVID-19) has caused a series of challenges to public health. One such challenge is the management of chronic diseases such as epilepsy during an epidemic event. Studies on this topic are rather limited and the related medical practice is full of uncertainty. Here we review recent development of potential approaches for epilepsy control during an epidemic and propose a new three-level management framework to address these challenges.


title: Sub-national variation in measles vaccine coverage and outbreak risk: a case study from a 2010 outbreak in Malawi

text: BACKGROUND: Despite progress towards increasing global vaccination coverage, measles continues to be one of the leading, preventable causes of death among children worldwide. Whether and how to target sub-national areas for vaccination campaigns continues to remain a question. We analyzed three metrics for prioritizing target areas: vaccination coverage, susceptible birth cohort, and the effective reproductive ratio (R(E)) in the context of the 2010 measles epidemic in Malawi. METHODS: Using case-based surveillance data from the 2010 measles outbreak in Malawi, we estimated vaccination coverage from the proportion of cases reporting with a history of prior vaccination at the district and health facility catchment scale. Health facility catchments were defined as the set of locations closer to a given health facility than to any other. We combined these estimates with regional birth rates to estimate the size of the annual susceptible birth cohort. We also estimated the effective reproductive ratio, R(E), at the health facility polygon scale based on the observed rate of exponential increase of the epidemic. We combined these estimates to identify spatial regions that would be of high priority for supplemental vaccination activities. RESULTS: The estimated vaccination coverage across all districts was 84%, but ranged from 61 to 99%. We found that 8 districts and 354 health facility catchments had estimated vaccination coverage below 80%. Areas that had highest birth cohort size were frequently large urban centers that had high vaccination coverage. The estimated R(E) ranged between 1 and 2.56. The ranking of districts and health facility catchments as priority areas varied depending on the measure used. CONCLUSIONS: Each metric for prioritization may result in discrete target areas for vaccination campaigns; thus, there are tradeoffs to choosing one metric over another. However, in some cases, certain areas may be prioritized by all three metrics. These areas should be treated with particular concern. Furthermore, the spatial scale at which each metric is calculated impacts the resulting prioritization and should also be considered when prioritizing areas for vaccination campaigns. These methods may be used to allocate effort for prophylactic campaigns or to prioritize response for outbreak response vaccination.


title: Viral etiology of medically attended influenza‐like illnesses in children less than five years old in Suzhou, China, 2011–2014

text: Limited information is available on the non‐influenza etiology and epidemiology of influenza‐like illness (ILI) in China. From April 2011 to March 2014, we collected oropharyngeal swabs from children less than 5 years of age with symptoms of ILI who presented to the outpatient departments of Suzhou University Affiliated Children's Hospital (SCH). We used reverse transcription polymerase chain reaction (rt‐PCR) or PCR to detect 11 respiratory viruses. Among 3,662 enrolled ILI patients, 1,292 (35.3%) tested positive for at least one virus. Influenza virus (16.9%) was detected most frequently (influenza A 7.4%, influenza B 9.5%), followed by respiratory syncytial virus (RSV) (5.6%), parainfluenza virus (PIV) types 1–4 (4.8%), human bocavirus (HBoV) (3.8%), human metapneumovirus (HMPV) (3.5%), and adenovirus (ADV) (3.0%). Co‐infections were identified in 108 (2.9%) patients. Influenza virus predominantly circulated in January–March and June–July. The 2013–2014 winter peaks of RSV and influenza overlapped. Compared with other virus positive cases, influenza positive cases were more likely to present with febrile seizure, and RSV positive cases were more likely to present with cough and wheezing, and were most frequently diagnosed with pneumonia. These data provide a better understanding of the viral etiology of ILI among children less than 5 years of age in Suzhou, China. Influenza is not only the most frequently identified pathogen but it is also the only vaccine preventable illness among the 11 pathogens tested. Such findings suggest the potential value of exploring value of influenza vaccination among this influenza vaccination target group. J. Med. Virol. 88:1334–1340, 2016. © 2016 Wiley Periodicals, Inc.


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title: SARS-Cov-2 and environmental protection: A collective psychology agenda for environmental psychology research

text: While the virus SARS-CoV-2 spreads all over the world, most countries have taken severe measures to protect their citizens and slow down the further spread of the disease COVID-19. These measures affect individuals, communities, cities, countries, and the entire planet. In this paper, we propose that the tremendous consequences of the corona crisis invite environmental psychology to focus more strongly on research questions that address major societal challenges from a collective psychology perspective. In particular, we stress that the corona crisis may affect how people appraise – and potentially respond to – the looming climate crisis. By consistently pointing out systemic links and their human factor, environmental psychology can become central to a scientific agenda of a sustainable ‘post-corona society’. In order to provide a framework for future research towards a sustainable societal transformation, we build on the Social Identity Model of Pro-Environmental Action (SIMPEA) and extend its scope to understand people's responses following the corona crisis. The model allows predictions of previously not explicitly included concepts of place attachment, nature connectedness, basic psychological needs, and systems thinking. It may serve as a guiding framework for a better understanding of the transformation towards a sustainable future.


title: INCIDENCE OF ARRHYTHMIAS AND ELECTROCARDIOGRAPHIC ABNORMALITIES IN SYMPTOMATIC PEDIATRIC PATIENTS WITH PCR POSITIVE SARS-CoV-2 INFECTION INCLUDING DRUG INDUCED CHANGES IN THE CORRECTED QT INTERVAL (QTc).

text: BACKGROUND: There is limited data regarding the electrophysiological abnormalities and arrhythmias in children with COVID-19, including those associated with treatment using potentially pro-arrhythmic Hydroxychloroquine (HCQ) and Azithromycin (AZN). OBJECTIVES: To describe the electrophysiologic findings and arrhythmias associated with pediatric COVID-19 and its treatment. METHODS: A single center retrospective chart review was undertaken and included all patients with 1) symptoms of COVID-19, and 2) PCR (+) nasopharyngeal swabs for SARS-CoV-2 who were placed on continuous telemetry for the duration of their hospitalization during March through May, 2020. RESULTS: Thirty-six patients were included in the study. Significant arrhythmias were found in 6 (non-sustained (ns) ventricular tachycardia in 5 and sustained atrial tachycardia in 1). All were self-resolving and half prompted prophylactic anti-arrhythmic therapy. Patients with significant arrhythmias were likely to have non-cardiac co-morbidities (4/6), but these were not more common than in patients without arrhythmias (20/30, p=1). The use of HCQ with or without AZN was associated with statistically significant QTc prolongation (411+19 msec vs 426+15 msec, p<0.0001). QTc was not statistically different in patients with and without arrhythmias (425+15 msec vs 425+15 msec, p=1). CONCLUSIONS: In pediatric patients with PCR positive active COVID-19 infection, significant arrhythmias are infrequent, but more common than expected in a general pediatric population. Comorbidities are not more common in patients with arrhythmias than in patients without arrhythmias. COVID-19 treatment using HCQ is associated with QTc prolongation, but was not associated with arrhythmias in pediatric patients.


title: Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis)

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an exponentially increasing number of coronavirus disease 19 (COVID-19) cases globally. Prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of COVID-19 animal models that enable accurate, quantifiable, and reproducible measurement of COVID-19 pulmonary disease free from observer bias. We first used serial computed tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities) at typical locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We then used positron emission tomography (PET) analysis to demonstrate increased FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. PET/CT imaging findings appeared in all macaques as early as 2 days post-exposure, variably progressed, and subsequently resolved by 6–12 days post-exposure. Finally, we applied operator-independent, semi-automatic quantification of the volume and radiodensity of CT abnormalities as a possible primary endpoint for immediate and objective efficacy testing of candidate medical countermeasures.


title: Atypical presentations of MERS-CoV infection in immunocompromised hosts

text: Abstract During the 2015 Korean MERS outbreak, we experienced atypical presentations of MERS-CoV infections in three immunocompromised hosts that warranted exceptional management. Case 1 showed delayed symptom development after a four-day asymptomatic period, Case 2 experienced a 20-day incubation period, and Case 3 exhibited persistent viral shedding without clinical deterioration. Recognizing these exceptions is extremely important in the management of MERS-CoV-exposed or -infected patients and for control of potential MERS outbreaks.


Apremilast as a potential treatment option for COVID‐19: no symptoms of infection in a psoriatic patient


docid: cuyboyqc

title: Harnessing self-assembled peptide nanoparticles in epitope vaccine design

text: Abstract Vaccination has been one of the most successful breakthroughs in medical history. In recent years, epitope-based subunit vaccines have been introduced as a safer alternative to traditional vaccines. However, they suffer from limited immunogenicity. Nanotechnology has shown value in solving this issue. Different kinds of nanovaccines have been employed, among which virus-like nanoparticles (VLPs) and self-assembled peptide nanoparticles (SAPNs) seem very promising. Recently, SAPNs have attracted special interest due to their unique properties, including molecular specificity, biodegradability, and biocompatibility. They also resemble pathogens in terms of their size. Their multivalency allows an orderly repetitive display of antigens on their surface, which induces a stronger immune response than single immunogens. In vaccine design, SAPN self-adjuvanticity is regarded an outstanding advantage, since the use of toxic adjuvants is no longer required. SAPNs are usually composed of helical or β-sheet secondary structures and are tailored from natural peptides or de novo structures. Flexibility in subunit selection opens the door to a wide variety of molecules with different characteristics. SAPN engineering is an emerging area, and more novel structures are expected to be generated in the future, particularly with the rapid progress in related computational tools. The aim of this review is to provide a state-of-the-art overview of self-assembled peptide nanoparticles and their use in vaccine design in recent studies. Additionally, principles for their design and the application of computational approaches to vaccine design are summarized.


title: A Review of Respiratory System Anatomy, Physiology, and Disease in the Mouse, Rat, Hamster, and Gerbil

text: The purpose of this article is to provide for practitioners a comprehensive overview of respiratory diseases, both infectious and noninfectious, in the mouse, rat, hamster, and gerbil. The information presented will also be useful for veterinarians pursuing board certification. Anatomy and physiology are briefly addressed, as those two facets alone could encompass an entire article for these species.


title: Anatomical distribution of respiratory tract leukocyte cell subsets in neonatal calves

text: Neonatal calves are highly susceptible to a number of diseases including those that infect via the mucosal surfaces of the respiratory and gastrointestinal tracts. In order to determine appropriate vaccine design and delivery systems, or to identify suitable immunostimulatory methods to combat these infections, a detailed understanding of the immune cell populations present at clinically relevant sites is key. Few studies have assessed the immune cell composition of the neonatal calf lung and comparisons with circulating immune cells in the blood are lacking. We describe immune cell populations present in the peripheral blood, bronchoalveolar lavage (BAL) fluid and lung tissue of young disease-free calves. Flow cytometric analysis revealed significant differences in cell subset distribution between the peripheral blood and respiratory tract, and between compartments within the respiratory tract. Notably, whereas WC1(+) γδ TCR + T lymphocytes dominate the peripheral blood, both the BAL fluid and lung tissue contained a high proportion of myeloid cells which expressed CD14 and CD172a (SIRPα). Very low numbers of tissue myeloid cells expressed MHC Class II in comparison to circulating myeloid cells in the blood. Respiratory tract tissues had low frequencies of CD4+ and CD8 + T lymphocytes, which were significantly lower than in the blood. Differences in the proportion of NKp46+ natural killer cells were also observed between tissue compartments. In order to target vaccines or immunostimulatory therapeutics appropriately, these differences in immune cell populations in tissue compartments should be taken into consideration.


title: Epidemiologic characteristics of scrub typhus on Jeju Island

text: OBJECTIVES: Scrub typhus is the most common febrile disease in Korea during the autumn. Jeju Island is the largest island in South Korea and has a distinctive oceanic climate. This study aimed to identify epidemiologic characteristics of scrub typhus on Jeju Island. METHODS: From January 2011 to December 2016, 446 patients were diagnosed with scrub typhus on Jeju Island. The patients’ personal data and the environmental factors that might be related to scrub typhus were investigated and retrospectively analyzed. RESULTS: The median age of the patients was 58-years-old (range, 8 to 91) and 43% of them worked in the agricultural, forestry or livestock industry. Regardless of their job, 87% of the patients had a history of either working outdoors or of other activities before developing scrub typhus. The south and southeast regions of Jeju Island, especially Namwon-eup, showed the highest incidence of scrub typhus. Workers in mandarin orange orchards seemed to be the highest risk group for scrub typhus infection. CONCLUSIONS: Scrub typhus on Jeju Island showed unique characteristics. To efficiently prevent scrub typhus, each year individual regional approaches should be developed based on the epidemiologic characteristics of the disease.


title: Grinding of alumina ceramic with microtextured brazed diamond end grinding wheels

text: Brazed monolayer diamond grinding wheels have advantages of a high abrasive bonding strength, high protrusion, and a large chip disposal space. However, it is difficult to prepare ordered and fine-grained brazed diamond grinding wheels. This study presents a new method for grain-arranged, brazed diamond grinding wheels with microtextures with similar performance to ordered and fine-grained brazed diamond grinding wheels. First, coarse diamond grains (18/20 mesh) were orderly brazed to fabricate the end grinding wheels. Next, a series of microtextures were ablated on the diamond grains using a pulsed laser, and two types of textured end grinding wheels—TG-G (ablated microgrooves only) and TG-GH (ablated microgrooves and microholes)—were prepared. Then, an experiment involving the grinding of alumina ceramics was performed, and the grinding characteristics and grinding mechanism were analyzed. The results indicated that compared with untextured diamond end grinding wheels (TG), the textured diamond grinding wheels (TG-G and TG-GH) significantly reduced the grinding force and the roughness of the machined surface. The local stress concentration at the microtextures promoted the formation of microcracks in the diamond grains of TG-G and TG-GH, and the self-sharpness of the grinding wheel was significantly improved. The brittle fracture mode of ceramic materials in grinding included intergranular fracture and transgranular fracture. Ironing pressure action was a key material-removal mechanism. It had an important influence on the cutting force and plasticity characteristics of the TG machined surface. For the surfaces processed by TG-G and TG-GH, the effect of ironing was weakened, while shearing played a more important role. The TG-GH grinding wheel ablated with microgrooves and microholes was superior to the TG-G grinding wheel ablated with only microgrooves, with regard to the grinding force, roughness, and self-sharpening.


title: Identification of the structural proteins of turkey enteric coronavirus

text: Coronaviruses in the intestinal contents of turkey poults from Quebec flocks with outbreaks of enteritis were detected by electron microscopy. Five isolates were serially propagated in embryonic turkey eggs by inoculation of clarified intestinal contents into the amniotic cavity. Viral particles contained in the intestinal contents of infected embryos were purified by differential and isopycnic centrifugation in sucrose gradients. Intact virions present in fractions of densities 1.18 to 1.20 g/ml were precipitated with trichloroacetic acid and the protein content was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. At least seven polypeptides with molecular weights ranging from 27,000 to 180,000 were regularly detected after electrophoresis of SDS-solubilized virions. Homologous rabbit antisera to turkey coronaviruses and pooled sera from convalescent turkeys immunochemically stained five polypeptides of apparent molecular weights of 95,000, 72–75,000, 66,000, 52,000 and 27,000. A further polypeptide with a molecular weight of 140,000 appeared in the absence of 2-mercaptoethanol and probably represents a dimer of the 66,000 polypeptide. One Quebec isolate differed from the Minnesota strain by two of its polypeptides, but no antigenic variations could be demonstrated amongst the various isolates either by immuno-electron microscopy, hemagglutination inhibition, or enzyme immuno assays on nitrocellulose.


title: Takotsubo Syndrome in the Setting of COVID-19 Infection

text: Abstract: A 58 year old woman was admitted with symptoms of COVID-19. She subsequently developed mixed shock and echocardiogram showed mid-distal left ventricular hypokinesis and apical ballooning, findings typical for stress, or Takotsubo, cardiomyopathy. Over the next few days her left ventricular function improved, further supporting reversibility of acute stress cardiomyopathy.


title: Identifying epitopes of HIV-1 that induce protective antibodies

text: During the past 20 years, the pendulum of opinion in the HIV-1 vaccine field has swung between two extremes, initially favouring the induction of antibodies only, and subsequently favouring the induction of cell-mediated immune responses only. At present, the consensus seems to be that induction of both humoral and cellular immunity by an HIV-1 vaccine will be required to achieve maximum protection. One obstacle to the development of an effective HIV-1 vaccine has been the difficulty in inducing broadly reactive, potent antibodies with protective functions. Defining epitopes and designing immunogens that will induce these antibodies is one of the main challenges that now confronts the HIV-1 vaccine field.


title: Impact of COVID‐19 on blood centres in Zhejiang province China

text: BACKGROUND AND OBJECTIVES: A worldwide pandemic of coronavirus disease 2019 (COVID‐19) has affected millions of people. A ‘closed‐off management’ protocol has been launched nationwide in China to cope with this major public health emergency. However, these procedures may cause a crisis for blood donation and blood supply. In this study, we assessed the impact of the COVID‐19 pandemic on blood donation and supply in Zhejiang province, which could provide reference and insight for developing countermeasures in other countries. MATERIALS AND METHODS: Blood donor and supply information from 38 blood centres during the Spring Festival of 2019 and 2020 were reviewed. A self‐administered questionnaire was carried out. RESULTS: Due to the COVID‐19 pandemic, the number of whole blood donors dropped by 67%. The success rate of recruitment for donations dropped by 60%. Most respondents (81·2%) were worried about the ‘possibility of acquiring COVID‐19 during blood donation’. The total amount of RBCs supply dropped by 65%. In the first week of the outbreak, the weekly amount of issued RBC units (10171·5 u) was almost six times higher than the collected units (1347·5 u). The mean haemoglobin value for RBCs transfusion was about 6·3 g/dl. About 4% of RBCs and 2·8% of frozen plasma were used in COVID‐19 patients. CONCLUSION: The secondary consequences of the COVID‐19 pandemic are blood shortages caused by the unavailability of blood donors, and this is likely to be replicated in many countries with high burdens of COVID‐19. Practical actions to broaden sources and reduce use for the global crisis must be taken proactively.


title: Nicotine and Opioids: a Call for Co-treatment as the Standard of Care

text: The U.S. is in the midst of an opioid epidemic. At the same time, tobacco use remains the leading cause of preventable death and disability. While the shared biological underpinnings of nicotine and opioid addiction are well established, clinical implications for co-treatment of these two substance use disorders has not been emphasized in the literature, nor have researchers, clinicians, and policy makers adequately outlined pathways for incorporating co-treatment into existing clinical workflows. The current brief review characterizes the metabolic and neural mechanisms which mediate co-use of nicotine and opioids, and then outlines clinical and policy implications for concurrently addressing these two deadly epidemics. Screening, assessment, medication-assisted treatment (MAT), and tobacco-free policy are discussed. The evidence suggests that clinical care and policies that facilitate co-treatment are an expedient means of delivering healthcare to individuals that result in better health for the population while also meeting patients’ substance abuse disorder recovery goals.


title: The Underlying Mechanism of 3-Hydroxyphthalic Anhydride-Modified Bovine Beta-Lactoglobulin to Block Human Papillomavirus Entry Into the Host Cell

text: We have previously demonstrated that 3-hydroxyphthalic anhydride (3HP)-modified bovine beta-lactoglobulin (3HP-β-LG) is highly effective in inhibiting entry of pseudovirus (PsV) of high- and low-risk human papillomavirus (HPV) into the target cell. Intravaginally applied 3HP-β-LG-containing vaginal gel could significantly inhibit HPV infection and reduce viral load in the cervical region. However, we still do not understand the underlying molecular mechanism by which 3HP-β-LG is able to inhibit HPV infection. Here, though, we showed that 3HP-β-LG did not inactivate HPV PsV, but rather blocked entry of HPV PsV into the target cell via its interaction with virus, not cell. It bound to the positively charged region in the HPV L1 protein, suggesting that 3HP-β-LG binds to HPV L1 protein through the interaction between the negatively charged region in 3HP-β-LG and the positively charged region in HPV L1 protein, thus competitively blocking the binding of HPV to the receptor on the basement membrane in vaginal mucosa. Although 3HP-modified chicken ovalbumin (3HP-OVA) also carries high net negative charges, it exhibited no anti-HPV activity, suggesting that the interaction between 3HP-modified protein and HPV L1 protein relies on both electrostatic and matchable conformation of the binding sites in both proteins. When topically applied, 3HP-β-LG did not enter the host cell or blood circulation. These findings suggest that 3HP-β-LG targets HPV L1 protein and blocks HPV entry into the host cell, thus being safe and effective for topical application in the treatment of HPV infection.


title: The global spread of Middle East respiratory syndrome: an analysis fusing traditional epidemiological tracing and molecular phylodynamics

text: BACKGROUND: Since its discovery in 2012, over 1700 confirmed cases of Middle East Respiratory Syndrome (MERS) have been documented worldwide and more than a third of those cases have died. While the greatest number of cases has occurred in Saudi Arabia, the recent export of MERS-coronavirus (MERS-CoV) to Republic of Korea showed that a pandemic is a possibility that cannot be ignored. Due to the deficit of knowledge in transmission methodology, targeted treatment and possible vaccines, understanding this virus should be a priority. Our aim was to combine epidemiological data from literature with genetic information from viruses sequenced around the world to present a phylodynamic picture of MERS spread molecular level to global scale. METHODS: We performed a qualitative meta-analysis of all laboratory confirmed cases worldwide to date based on literature, with emphasis on international transmission and healthcare associated infections. In parallel, we used publicly available MERS-CoV genomes from GenBank to create a phylogeographic tree, detailing geospatial timeline of viral evolution. RESULTS: Several healthcare associated outbreaks starting with the retrospectively identified hospital outbreak in Jordan to the most recent outbreak in Riyadh, Saudi Arabia have occurred. MERS has also crossed many oceans, entering multiple nations in eight waves between 2012 and 2015. In this paper, the spatiotemporal history of MERS cases, as documented epidemiologically, was examined by Bayesian phylogenetic analysis. Distribution of sequences into geographic clusters and interleaving of MERS-CoV sequences from camels among those isolated from humans indicated that multiple zoonotic introductions occurred in endemic nations. We also report a summary of basic reproduction numbers for MERS-CoV in humans and camels. CONCLUSION: Together, these analyses can help us identify factors associated with viral evolution and spread as well as establish efficacy of infection control measures. The results are especially pertinent to countries without current MERS-CoV endemic, since their unfamiliarity makes them particularly susceptible to uncontrollable spread of a virus that may be imported by travelers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s41256-016-0014-7) contains supplementary material, which is available to authorized users.