title: Emerging Regulatory Roles of Dual-Specificity Phosphatases in Inflammatory Airway Disease

text: Inflammatory airway disease, such as asthma and chronic obstructive pulmonary disease (COPD), is a major health burden worldwide. These diseases cause large numbers of deaths each year due to airway obstruction, which is exacerbated by respiratory viral infection. The inflammatory response in the airway is mediated in part through the MAPK pathways: p38, JNK and ERK. These pathways also have roles in interferon production, viral replication, mucus production, and T cell responses, all of which are important processes in inflammatory airway disease. Dual-specificity phosphatases (DUSPs) are known to regulate the MAPKs, and roles for this family of proteins in the pathogenesis of airway disease are emerging. This review summarizes the function of DUSPs in regulation of cytokine expression, mucin production, and viral replication in the airway. The central role of DUSPs in T cell responses, including T cell activation, differentiation, and proliferation, will also be highlighted. In addition, the importance of this protein family in the lung, and the necessity of further investigation into their roles in airway disease, will be discussed.


title: A longitudinal study of the dynamics of bovine corona virus and respiratory syncytial virus infections in dairy herds

text: Abstract The objective of this study was to examine the dynamics of bovine corona virus (BCV) and bovine respiratory syncytial virus (BRSV) infections in dairy herds over a 3-year period. The status of 79 dairy herds located in two Northern and two Southern Regions of Sweden were surveyed by measuring antibody concentrations to BCV and BRSV in pooled milk samples from primiparous cows, and in bulk-tank milk twice annually. In the Southern Regions the percentage of antibody-positive herds remained persistently high (75–100%), whereas in herds based in the Northern Region, the percentage of positive herds for BCV and BRSV was 38–80% and 0–80%, respectively, with antibody levels to BRSV decreasing over time. Pooled milk samples of ‘home-bred’ primiparous animals were found to be most useful in terms of monitoring herd status but could gradually be replaced by bulk-tank sampling once freedom from infection was established.


title: Empirical Treatment and Prevention of COVID-19

text: The rapid spread of severe acute respiratory coronavirus syndrome 2 (SARS-CoV-2) in the population and throughout the cells within our body has been developing. Another major cycle of coronavirus disease 2019 (COVID-19), which is expected in the coming fall, could be even more severe than the current one. Therefore, effective countermeasures should be developed based on the already obtained clinical and research information about SARS-CoV-2. The aim of this review was to summarize the data on the empirical treatment of COVID-19 acquired during this SARS-CoV-2 infection cycle; this would aid the establishment of an appropriate healthcare policy to meet the challenges in the future. The infectious disease caused by SARS-CoV-2 is characterized by common cold along with hypersensitivity reaction. Thus, in addition to treating common cold, it is essential to minimize the exposure of cells to the virus and to mitigate the uncontrolled immune response. A proper combination of antiviral agents, immune modulators such as prednisolone, and anticoagulants such as heparin and anti-C5a antagonists could be employed to minimize lung damage and prevent systemic involvements. Finally, strategies to achieve population immunity against SARS-CoV-2 should be developed through understanding of the interaction between the immune system and the virus.


title: A preference driven multi-criteria optimization tool for HVAC design and operation

text: Abstract This paper discusses the issue of selecting the design solution that best accords with an articulated preference of multiple criteria with an acceptable performance band. The application of a newly developed multi-criteria decision-making tool called RR-PARETO2 is presented. An example of HVAC design is used to illustrate how solutions could be selected within a multi-criteria optimization framework. In this example, five criteria have been selected, namely, power consumption, thermal comfort, risk of airborne infection of influenza and tuberculosis and effective differential temperature (Δt eq) of body parts. The goal is to select the optimal air exchange rate that makes reasonable trade-offs among all the objectives. Two scenarios have been studied. In the first scenario, there is an influenza outbreak and the important objective is to prevent the spread of infection. In the second scenario, energy prices are high and the primary objective is to reduce energy. In both scenarios, RR-PARETO2 algorithm selects solutions that make reasonable trade-offs among conflicting objectives. The example illustrates how objectives such as reduction of airborne disease transmission and maximizing thermal comfort can be incorporated in the design of a practical, full-scale HVAC system.


title: Psoriatic Arthritis and COVID‐19 Pandemic: Consequences in Medical Treatment?

text: The COVID‐19 pandemic has a strong negative impact on human society world‐wide. Patients with immune‐mediated disease may be prone to an increased risk of infection and/ or more severe course. We review the available data for patients with psoriatic arthritis (PSA) and systemic treatments. Current treatment options are summarized. Based upon the experience with COVID‐19 the following problems are addressed: (a) Can systemic treatment reduce comorbidities of PsA that are also comorbidities for COVID‐19? Does systemic medical treatment pose an increased risk of infection with SARS‐CoV‐2? Does systemic drug therapy have an impact on the risk of pulmonary fibrosis ‐ a factor with strong negative impact on COVID‐19 outcome? Small molecules, inhibitors of tumor necrosis factor alfa, interleukin and JAK inhibitors are considered. The data are inhomogeneous for the multiple drugs used in PsA. Although the risk for severe upper airway tract infections during clinical controlled trials was mostly in the range of placebo, these data have been obtained before the COVID‐19 pandemic and should be interpreted with caution. Some biologics demonstrated an anti‐fibrotic activity in vitro and in animal disease models. None of the biologics is indicated during an active infection with fever. In non‐symptomatic PsA patients, systemic drug therapy can be continued. This article is protected by copyright. All rights reserved.


title: How scientific research reacts to international public health emergencies: a global analysis of response patterns

text: As of the middle of April 2020, the unprecedented COVID-19 pandemic has claimed more than 137,000 lives (https://coronavirus.jhu.edu/map.html). Because of its extremely fast spreading, the attention of the global scientific community is now focusing on slowing down, containing and finally stopping the spread of this disease. This requires the concerted action of researchers and practitioners of many related fields, raising, as always in such situations the question, of what kind of research has to be conducted, what are the priorities, how has research to be coordinated and who needs to be involved. In other words, what are the characteristics of the response of the global research community on the challenge? In the present paper, we attempt to characterise, quantify and measure the response of academia to international public health emergencies in a comparative bibliometric study of multiple outbreaks. In addition, we provide a preliminary review of the global research effort regarding the defeat of the COVID-19 pandemic. From our analysis of six infectious disease outbreaks since 2000, including COVID-19, we find that academia always responded quickly to public health emergencies with a sharp increase in the number of publications immediately following the declaration of an outbreak by the WHO. In general, countries/regions place emphasis on epidemics in their own region, but Europe and North America are also concerned with outbreaks in other, developed and less developed areas through conducting intensive collaborative research with the core countries/regions of the outbreak, such as in the case of Ebola in Africa. Researches in the fields of virology, infectious diseases and immunology are the most active, and we identified two characteristic patterns in global science distinguishing research in Europe and America that is more focused on public health from that conducted in China and Japan with more emphasis on biomedical research and clinical pharmacy, respectively. Universities contribute slightly less than half to the global research output, and the vast majority of research funding originates from the public sector. Our findings on how academia responds to emergencies could be beneficial to decision-makers in research and health policy in creating and adjusting anti-epidemic/-pandemic strategies.


title: A complete protocol for whole-genome sequencing of virus from clinical samples: Application to coronavirus OC43

text: Abstract Genome sequencing of virus has become a useful tool for better understanding of virus pathogenicity and epidemiological surveillance. Obtaining virus genome sequence directly from clinical samples is still a challenging task due to the low load of virus genetic material compared to the host DNA, and to the difficulty to get an accurate genome assembly. Here we introduce a complete sequencing and analyzing protocol called V-ASAP for Virus Amplicon Sequencing Assembly Pipeline. Our protocol is able to generate the viral dominant genome sequence starting from clinical samples. It is based on a multiplex PCR amplicon sequencing coupled with a reference-free analytical pipeline. This protocol was applied to 11 clinical samples infected with coronavirus OC43 (HcoV-OC43), and led to seven complete and two nearly complete genome assemblies. The protocol introduced here is shown to be robust, to produce a reliable sequence, and could be applied to other virus.


title: Crosstalk between innate and adaptive immune responses to infectious bronchitis virus after vaccination and challenge of chickens varying in serum mannose-binding lectin concentrations

text: Mannose-binding lectin (MBL), a C-type collectin with structural similarities to C1q, is an innate pattern-recognition molecule that is sequestered to sites of inflammation and infections. MBL selectively binds distinct chemical patterns, including carbohydrates expressed on all kinds of pathogens. The present study shows that serum MBL levels influence the ability of chickens to clear the respiratory tract of virus genomes after an infectious bronchitis virus (IBV) infection. The primary IBV infection induced changes in circulating T-cell populations and in the specific antibody responses. Serum MBL levels also influenced IBV vaccine-induced changes in circulating T-cell populations. Moreover, addition of mannose to an IBV vaccine altered both vaccine-induced changes in circulating T-cell populations and IBV specific vaccine and infection-induced antibody responses in chickens with high serum MBL levels. These data demonstrate that MBL is involved in the regulation of the adaptive immune response to IBV.


title: Vitrification after multiple rounds of sample application and blotting improves particle density on cryo-electron microscopy grids

text: Single particle cryo-electron microscopy (cryoEM) is becoming widely adopted as a tool for structural characterization of biomolecules at near-atomic resolution. Vitrification of the sample to obtain a dense distribution of particles within a single field of view remains a major bottleneck for the success of such experiments. Here, we describe a simple and cost-effective method to increase the density of frozen-hydrated particles on grids with holey carbon support films. It relies on performing multiple rounds of sample application and blotting prior to plunge freezing in liquid ethane. We show that this approach is generally applicable and significantly increases particle density for a range of samples, such as small protein complexes, viruses and filamentous assemblies. The method is versatile, easy to implement, minimizes sample requirements and can enable characterization of samples that would otherwise resist structural studies using single particle cryoEM.


title: Neonates with reduced neonatal lung function have systemic low-grade inflammation

text: Background Children and adults with asthma and impaired lung function have been reported to have low-grade systemic inflammation, but it is unknown whether this inflammation starts before symptoms and in particular whether low-grade inflammation is present in asymptomatic neonates with reduced lung function. Objective We sought to investigate the possible association between neonatal lung function and biomarkers of systemic inflammation. Methods Plasma levels of high-sensitivity C-reactive protein (hs-CRP), IL-1β, IL-6, TNF-α, and CXCL8 (IL-8) were measured at age 6 months in 300 children of the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort who had completed neonatal lung function testing at age 4 weeks. Associations between neonatal lung function indices and inflammatory biomarkers were investigated by conventional statistics and unsupervised principal component analysis. Results The neonatal forced expiratory volume at 0.5 seconds was inversely associated with hs-CRP (β-coefficient, −0.12; 95% CI, −0.21 to −0.04; P < .01) and IL-6 (β-coefficient, −0.10; 95% CI, −0.18 to −0.01; P = .03) levels. The multivariate principal component analysis approach, including hs-CRP, IL-6, TNF-α, and CXCL8, confirmed a uniform upregulated inflammatory profile in children with reduced forced expiratory volume at 0.5 seconds (P = .02). Adjusting for body mass index at birth, maternal smoking, older children in the home, neonatal bacterial airway colonization, infections 14 days before, and asthmatic symptoms, as well as virus-induced wheezing, at any time before biomarker assessment at age 6 months did not affect the associations. Conclusion Diminished neonatal lung function is associated with upregulated systemic inflammatory markers, such as hs-CRP.


title: Novel coronavirus: From discovery to clinical diagnostics

text: Abstract A novel coronavirus designated as 2019-nCoV first appeared in Wuhan, China in late December 2019. Dozens of people died in China, and thousands of people infected as 2019-nCoV continues to spread around the world. We have described the discovery, emergence, genomic characteristics, and clinical diagnostics of 2019-nCoV.


title: The COVID-19 Pandemic and Physical Activity

text: Abstract The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune, respiratory, cardiovascular, musculoskeletal systems and the brain. The cellular mechanisms and danger of this “second wave” effect of COVID-19 to the human body, along with the effects of aging, proper nutrition, and regular physical activity, are reviewed in this editorial article.


title: Infectious Triggers of Chronic Lung Allograft Dysfunction

text: Survival after lung transplantation is limited in large part due to the high incidence of chronic rejection, known as chronic lung allograft dysfunction (CLAD). Pulmonary infections are a frequent complication in lung transplant recipients, due both to immunosuppressive medications and constant exposure of the lung allograft to the external environment via the airways. Infection is a recognized risk factor for the development of CLAD, and both acute infection and chronic lung allograft colonization with microorganisms increase the risk for CLAD. Acute infection by community acquired respiratory viruses, and the bacteria Pseudomonas aeruginosa and Staphylococcus aureus are increasingly recognized as important risk factors for CLAD. Colonization by the fungus Aspergillus may also augment the risk of CLAD. Fostering this transition from healthy lung to CLAD in each of these infectious episodes is the persistence of an inflammatory lung allograft environment.


title: HAIKU: A Semantic Framework for Surveillance of Healthcare-Associated Infections

text: Abstract Healthcare-Associated Infections (HAI) impose a substantial health and financial burden. Surveillance for HAI is essential to develop and evaluate prevention and control efforts. The traditional approaches to HAI surveillance are often limited in scope and efficiency by the need to manually obtain and integrate data from disparate paper charts and information systems. The considerable effort required for discovery and integration of relevant data from multiple sources limits the current effectiveness of HAI surveillance. Knowledge-based systems can address this problem of contextualizing data to support integration and reasoning. In order to facilitate knowledge-based decision making in this area, availability of a reference vocabulary is crucial. The existing terminologies in this domain still suffer from inconsistencies and confusion in different medical/clinical practices, and there is a need for their further improvement and clarification. To develop a common understanding of the infection control domain and to achieve data interoperability in the area of hospital-acquired infections, we present the HAI Ontology (HAIO) to improve knowledge processing in pervasive healthcare environments, as part of the HAIKU (Hospital Acquired Infections – Knowledge in Use) system. The HAIKU framework assists physicians and infection control practitioners by providing recommendations regarding case detection, risk stratification and identification of diagnostic factors.


title: Structure and Inhibition of the SARS Coronavirus Envelope Protein Ion Channel

text: The envelope (E) protein from coronaviruses is a small polypeptide that contains at least one α-helical transmembrane domain. Absence, or inactivation, of E protein results in attenuated viruses, due to alterations in either virion morphology or tropism. Apart from its morphogenetic properties, protein E has been reported to have membrane permeabilizing activity. Further, the drug hexamethylene amiloride (HMA), but not amiloride, inhibited in vitro ion channel activity of some synthetic coronavirus E proteins, and also viral replication. We have previously shown for the coronavirus species responsible for severe acute respiratory syndrome (SARS-CoV) that the transmembrane domain of E protein (ETM) forms pentameric α-helical bundles that are likely responsible for the observed channel activity. Herein, using solution NMR in dodecylphosphatidylcholine micelles and energy minimization, we have obtained a model of this channel which features regular α-helices that form a pentameric left-handed parallel bundle. The drug HMA was found to bind inside the lumen of the channel, at both the C-terminal and the N-terminal openings, and, in contrast to amiloride, induced additional chemical shifts in ETM. Full length SARS-CoV E displayed channel activity when transiently expressed in human embryonic kidney 293 (HEK-293) cells in a whole-cell patch clamp set-up. This activity was significantly reduced by hexamethylene amiloride (HMA), but not by amiloride. The channel structure presented herein provides a possible rationale for inhibition, and a platform for future structure-based drug design of this potential pharmacological target.


title: Enfermedades infecciosas zoonóticas

text: Resumen En orden a efectuar una reflexión estructurada sobre lo que representan las zoonosis emergentes expondremos de manera deliberadamente sesgada los siguientes aspectos: en primer término, aludiremos a modo de introducción a determinados conceptos y características comunes al perfil de un agente emergente modelo; en segundo lugar, comentaremos los factores que contribuyen a facilitar la emergencia de las infecciones zoonóticas en el momento presente, y en última instancia, presentaremos de modo secuencial una reflexión sobre la vigilancia, la práctica médica asistencial y el papel de los laboratorios en este ámbito. Abstract To effect a structured review about what emerging zoonoses represent, we present the following aspects in a deliberately biased way: firstly, by way of introduction, we discuss certain concepts and characteristics common to the profile of an emergent agent; secondly, we comment on the factors that facilitate the emergence of zoonotic infections at present; and finally, we describe the surveillance, medical practice and laboratory work in this area.


title: Middle East Respiratory Syndrome Coronavirus Superspreading Event Involving 81 Persons, Korea 2015

text: Since the first imported case of Middle East respiratory syndrome coronavirus (MERS-CoV) infection was reported on May 20, 2015 in Korea, there have been 186 laboratory-confirmed cases of MERS-CoV infection with 36 fatalities. Ninety-seven percent (181/186) of the cases had exposure to the health care facilities. We are reporting a superspreading event that transmitted MERS-CoV to 81 persons at a hospital emergency room (ER) during the Korean outbreak in 2015. The index case was a 35-yr-old man who had vigorous coughing while staying at the ER for 58 hr. As in severe acute respiratory syndrome outbreaks, superspreading events can cause a large outbreak of MERS in healthcare facilities with severe consequences. All healthcare facilities should establish and implement infection prevention and control measure as well as triage policies and procedures for early detection and isolation of suspected MERS-CoV cases.


title: Drastic changes in the tissue-specific expression of secreted phospholipases A2 in chicken pulmonary disease

text: Infectious bronchitis is one of the most important diseases in poultry and it causes major economic losses. Infectious bronchitis is an acute, highly contagious, viral disease of chickens, characterized by rales, coughing, and sneezing. Because secreted phospholipases A2 (sPLA2) are involved in inflammatory processes, the gene expressions of sPLA2s were investigated in both healthy chickens and chickens with infectious bronchitis and lung inflammation. The draft chicken genome was first scanned using human sPLA2 sequences to identify chicken sPLA2s (ChPLA2), chicken total mRNA were isolated and RT-PCR experiments were performed to amplify and then sequence orthologous cDNAs. Full-length cDNA sequences of ChPLA2-IB, -IIA, -IIE, -V and -X were cloned. The high degree of sequence identity of 50–70% between the avian and mammalian (human and mouse) sPLA2 orthologs suggests a conservation of important enzymatic functions for these phospholipases. Quantitation by qPCR of the transcript levels of ChPLA2-IB, -IIA, -IIE, -V and -X in several tissues from healthy chicken indicated that the expression patterns and mRNA levels diverged among the phospholipases tested. In chicken with infectious bronchitis, an over expression of ChPLA2-V was observed in lungs and spleen in comparison with healthy chicken. These findings suggest that ChPLA2-V could be a potential biomarker for lung inflammation. Conversely, a down regulation of ChPLA2-IB, -IIA and -X was observed in lungs and spleen in case of infectious bronchitis. A significant increase in the expression level of ChPLA2-X and ChPLA2-IB was also noticed in pancreas. No or minor changes have been detected in the expression of ChPLA2-IIE in lungs and small intestine, but it shows a significant increase in several infected tissues.


title: The how and why of lncRNA function: An innate immune perspective

text: Abstract Next-generation sequencing has provided a more complete picture of the composition of the human transcriptome indicating that much of the “blueprint” is a vastness of poorly understood non-protein-coding transcripts. This includes a newly identified class of genes called long noncoding RNAs (lncRNAs). The lack of sequence conservation for lncRNAs across species meant that their biological importance was initially met with some skepticism. LncRNAs mediate their functions through interactions with proteins, RNA, DNA, or a combination of these. Their functions can often be dictated by their localization, sequence, and/or secondary structure. Here we provide a review of the approaches typically adopted to study the complexity of these genes with an emphasis on recent discoveries within the innate immune field. Finally, we discuss the challenges, as well as the emergence of new technologies that will continue to move this field forward and provide greater insight into the biological importance of this class of genes. This article is part of a Special Issue entitled: ncRNA in control of gene expression edited by Kotb Abdelmohsen.


title: Comparaison entre le nombre et la nature des clostridium fécaux et d'autres facteurs de risque impliqués dans la pathologie intestinale des nouveau-nés

text: Summary One-hundred and fifteen infants aged 1 to 31 days from two intensivecare units were grouped into 6 classes according to clinical criteria (enterocolitis with or without anatomopathological examination and pneumatosis intestinalis, ≪haemorrhagic colitis ≫, acute diarrhoea or absence of intestinal disorders). The total number of viable bacteria, the number of Clostridium and, in some cases, the presence of rota- and/or coronavirus were determined in their stools. The incidence of Clostridium in the stools of infants with enterocolitis (with or without pneumatosis intestinalis) or haemorrhagic colitis was not significantly different from that of infants without intestinal disorders, whereas stools of infants with acute diarrhoea less often contained Clostridium than those of other infants. C. butyricum, C. difficile, C. perfringens, C. tertium, and C. sordellii were identified. Correspondence analysis comparing the variable, ≪clinical profile≫, with 23 other variables, suggested that the variables of gemellity, a birth-weight below 1900 g, a gestational age of less than 35 weeks, respiratory distress, umbilical catheterization and a Clostridium count above 107/g at the onset of clinical signs, i.e. between 8 to 12 days of age, were linked to the clinical profile of necrotizing enterocolitis with pneumatosis intestinalis. Conversely, the absence of gemellity, a high birthweight and gestational age, the absence of respiratory distress or umbilical catheterization, the onset of diarrhoea within 8 days, and the presence of rota- and/or coronavirus in the stools were linked with a clinical profile of acute diarrhoea.


title: Coronaviruses in spinal fluid of patients with acute monosymptomatic optic neuritis

text: Acute monosymptomatic optic neuritis (AMON) may be an initial symptom of multiple sclerosis (MS). Coronaviruses have been implicated in the etiology of MS. The objective of the present study was to look for coronaviral RNA in AMON, which could be present in the initial stages of the development of MS. Material and methods ‐ Spinal fluids from 37 patients with AMON and 15 surgical control patients with protrusion of the intervertebral disk were assayed with a nested multiplex polymerase chain reaction with primers specific for human coronaviruses strain (HCV) 229E and OC43. Results ‐ Four patients and 1 control were positive for HCV‐229E. No evidence of HCV‐OC43 was found. The frequency of positive samples was low and there was no statistical difference between AMON and controls. Conclusion ‐ This study does not provide evidence for an etiological role of human coronaviruses in acute monosymptomatic optic neuritis.


Feeding our autonomy: resilience in the face of the CoVid-19 and future pandemics


title: The other side of the coin: Leveraging Epstein–Barr virus in research and therapy

text: Abstract Epstein-Barr virus is (EBV) a ubiquitous virus prevalent in 90% of the human population. Transmitted through infected saliva, EBV is the causative agent of infectious mononucleosis (IM) and is further implicated in malignancies of lymphoid and epithelial origins. In the past few decades, research efforts primarily focused on dissecting the mechanism of EBV-induced oncogenesis. Here, we present an alternate facet of the oncovirus EBV, on its applications in research and therapy. Finally, discussions on the prospective utilization of EBV in nasopharyngeal carcinoma (NPC) diagnosis and therapy will also be presented.


title: Tropical Diseases Definition, Geographic Distribution, Transmission, and Classification

text: The term tropical diseases encompasses all diseases that occur principally in the tropics. This term covers all communicable and noncommunicable diseases, genetic disorders, and disease caused by nutritional deficiencies or environmental conditions (such as heat, humidity, and altitude) that are encountered in areas that lie between, and alongside, the Tropic of Cancer and Tropic of Capricorn belts. In tropical countries, apart from noncommunicable diseases, a severe burden of disease is caused by an array of different microorganisms, parasites, land and sea animals, and arthropods.


title: Uncertainties on the prognostic value of D‐dimers in COVID‐19 patients

text: We read with great interest the paper by Zhang and colleagues [1], describing the predictive value of D-dimers tested on admission on in-hospital mortality in patients with Covid-19. These interesting results may supply an easy-to practice laboratory marker to clinical teams managing the patients. However, a number of uncertainties must be mentioned.


title: Fatal pneumonia and viremia due to human parainfluenza virus type 1 in a patient with adult T-cell leukemia–lymphoma treated with mogamulizumab

text: Abstract We report a case of fatal pneumonia and viremia due to human parainfluenza virus type 1 (HPIV-1) in a 65-year-old male patient with adult T-cell leukemia–lymphoma (ATL) treated with mogamulizumab, a brand-new therapeutic agent for ATL. To our knowledge, this is the first report describing viremia due to HPIV-1. After administering mogamulizumab, lymphocyte count in the blood was drastically decreased and the patient suffered from complicated infections including gram-negative bacterial sepsis, cytomegalovirus antigenemia and aspergillosis. Although these infections were successfully controlled by broad spectrum antimicrobial therapy, patchy ground-grass opacities in the both lungs were gradually worsened. He finally died due to acute respiratory failure. Since findings of the chest CT was consistent with typical patterns of viral pneumonia, we screened major respiratory viruses in the peripheral blood with multiplex PCR, and it turned out that RNA of HPIV-1 was positive. Although ATL cells were not detected in the autopsied lungs and a variety of other tissues, cytoplasmic inclusion bodies, which are commonly observed in RNA viral infection, were abundantly observed in the autopsied lung tissue. These findings suggest that mogamulizumab accomplished complete remission of ATL, while the chemotherapy-induced prolonged lymphopenia caused fatal pneumonia and viremia due to HPIV-1. As it has been well recognized that community respiratory viruses including HPIV-1 often cause fatal pneumonia in patients with leukemia, but also there is no specific treatment for HPIV-1, we have to enforce standard precautions especially when we treat leukemic patients with intensively immunosuppressive agents such as mogamulizumab.


title: A sensitive duplex nanoparticle-assisted PCR assay for identifying porcine epidemic diarrhea virus and porcine transmissible gastroenteritis virus from clinical specimens

text: In this study, a novel duplex nanoparticle-assisted polymerase chain reaction (nanoPCR) assay was developed to detect porcine epidemic diarrhea virus (PEDV) and porcine transmissible gastroenteritis virus (TGEV). Two pairs of primers were designed based on the conserved region within the N gene of PEDV and TGEV. In a screening of 114 clinical samples from four provinces in China for PEDV and TGEV, 48.2 and 3.5 % of the samples, respectively, tested positive. Under optimized conditions, the duplex nanoPCR assay had a detection limit of 7.6 × 10(1) and 8.5 × 10(1) copies μL(−1) for PEDV and TGEV, respectively. The sensitivity of the duplex nanoPCR assay was ten times higher than that of a conventional PCR assay. Moreover, no fragments were amplified when the duplex nanoPCR assay was used to test samples containing other porcine viruses. Our results indicate that the duplex nanoPCR assay described here is useful for the rapid detection of PEDV and TGEV and can be applied in clinical diagnosis.


An increased severity of peripheral arterial disease in the covid-19 era.


title: Clinical characteristics and outcomes of respiratory syncytial virus infection in pregnant women

text: OBJECTIVE: To describe the clinical presentation and laboratory diagnosis of pregnant women with respiratory syncytial virus (RSV) infection. METHODS: Pregnant women in their second and third trimester were enrolled during the course of routine prenatal care visits when they were asymptomatic within the preceding two weeks (healthy controls) or when they reported symptoms of acute respiratory illness (ARI) of ≤7 days of duration (cases). Clinical outcomes were assessed at enrollment and two weeks after. Re-enrollment was allowed. Nasal-pharyngeal secretions were evaluated for respiratory pathogens by real-time reverse transcription polymerase chain reaction (PCR). Sera were tested for RSV-specific antibody responses by Western Blot, microneutralization assay, and palivizumab competitive antibody assay. RESULTS: During the 2015–2016 respiratory virus season, 7 of 65 (11%) pregnant women with ARI at their initial enrollment and 8 of 77 (10%) pregnant women with ARI during the study period (initial or re-enrollment) had PCR-confirmed RSV infection. Four (50%) PCR-confirmed RSV ARI cases reported symptoms of a lower respiratory tract illness (LRTI), one was hospitalized. Combining PCR and serology data, the RSV attack rate at initial enrollment was 12% (8 of 65), and 13% (10 of 77) based on ARI episodes. Among healthy controls, 28 of 88 (32%) had a Western Blot profile suggestive of a recent RSV infection either in the prior and/or current season. CONCLUSION: RSV had an attack rate of 10–13% among ambulatory pregnant women receiving routine prenatal care during the respiratory virus season. The serology results of healthy controls suggest a potentially higher attack rate. Future studies should be aware of the combined diagnostic strength of PCR and serology to identify RSV infection. As maternal RSV vaccine candidates are evaluated to protect young infants, additional priority should be placed on outcomes of pregnant women.


Value of Analog in Medicine: Digital Compromise to Teach Old-Timer New Trick


title: CD4 T cell loss and Th2 and Th17 bias are associated with the severity of severe fever with thrombocytopenia syndrome (SFTS)

text: Abstract Severe fever with thrombocytopenia syndrome (SFTS) is a newly emerging infectious disease caused by a novel bunyavirus with high mortality. Immune suppression is thought to be crucial in disease progression. However, data on immune responses during SFTS are scarce. This study aimed to evaluate the changes in CD4 T-cell subsets throughout the entirety of infection and analyse their relationships with disease severity in SFTS patients. In parallel with CD4 T-cell depletion, decreased Th1, Th2 and Treg numbers, but comparable Th17-cell numbers, were observed in deceased patients compared with those in surviving patients. Additionally, increased Th2 and Th17-cell percentages in the residual CD4 T-cell population led to aberrant Th2/Th1 and Th17/Treg ratios, which were positively correlated with disease severity. Collectively, our data indicated that CD4 T-cell deficiency, Th2 and Th17 bias were closely correlated with the severity of SFTS, indicating therapeutic potential of early immune interventions to ameliorate disease severity.


title: Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission

text: BACKGROUND: The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness. RESULTS: Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations. CONCLUSION: Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus.


title: COVID‐19, Virtual Church Services and a New Temporary Geography of Home

text: The COVID‐19 pandemic and subsequent lockdown measures implemented by the United Kingdom government from 23 March 2020 led to unprecedented adaptations from individuals and communities including places of worship, their clergy and congregations. This paper through a multi‐disciplinary dialogue between human geography and theology explores the interrelations between place, space and the spiritual. It identifies the bricolage mechanisms that were developed rapidly by churches to shift towards providing virtual church services. This was an uncommon practice by Christian denominations in the UK. COVID‐19 changed the rules requiring new practices to emerge resulting in a new form of infrasecular space to emerge. Such rapid transformations through the provision of online services and virtual embeddedness blurred the lines between sacred and secular spaces. During virtual services, the minister’s home is temporally linked to the homes of congregants forming an intersacred space. Homes and spaces within homes are transformed into temporary sacred spaces.


title: Infection control for SARS in a tertiary paediatric centre in Hong Kong

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging infectious disease. After the appearance of an index patient in Hong Kong in February 2003, SARS outbreaks occurred rapidly in hospitals and spread to the community. The aim of this retrospective study is to evaluate the effectiveness of a triage policy and risk-stratified infection control measures in preventing nosocomial SARS infection among paediatric healthcare workers (HCWs) at the Prince of Wales Hospital, a general hospital to which children with SARS are referred in Hong Kong. The acute paediatric wards were stratified into three areas: (1) ultra high-risk area, (2) high-risk area and (3) moderate-risk area according to different risk levels of nosocomial SARS transmission. The implementation of different levels of infection control precautions was guided by this risk stratification strategy. Between 13 March and 23 June, 38 patients with probable and suspected SARS, 90 patients with non-SARS pneumonia, and 510 patients without pneumonia were admitted into our unit. All probable SARS cases were isolated in negative-pressure rooms. Twenty-six HCWs worked in the ultra high-risk area caring for SARS patients and 88 HCWs managed non-SARS patients in other ward areas. None of the HCWs developed clinical features suggestive of SARS. In addition, there was no nosocomial spread of SARS-associated coronavirus to other patients or visitors during this period. In conclusion, stringent infection control precautions, appropriate triage and prompt isolation of potential SARS patients may have contributed to a lack of nosocomial spread and HCW acquisition of SARS in our unit.


title: Review of the clinical significance of respiratory virus infections in newborn infants

text: Respiratory viruses have been recognised as causative agents for a wide spectrum of clinical manifestations and severe respiratory compromise in neonates during birth hospitalisation. Early‐life respiratory virus infections have also been shown to be associated with adverse long‐term consequences. CONCLUSION: Preventing virus infections by intensifying hygiene measures and cohorting infected infants should be a major goal for neonatal intensive care units, as well as more common use of virus diagnostics. Active virus surveillance and long‐term follow‐up are needed to ascertain the causality and exact underlying mechanisms for adverse long‐term consequences.


title: Hematological features of persons with COVID-19

text: We studied admission and dynamic demographic, hematological and biochemical co-variates in 1449 hospitalized subjects with coronavirus infectious disease-2019 (COVID-19) in five hospitals in Wuhan, Hubei province, China. We identified two admission co-variates: age (Odds Ratio [OR] = 1.18, 95% Confidence Interval [CI] [1.02, 1.36]; P = 0.026) and baseline D-dimer (OR = 3.18 [1.48, 6.82]; P = 0.003) correlated with an increased risk of death in persons with COVID-19. We also found dynamic changes in four co-variates, Δ fibrinogen (OR = 6.45 [1.31, 31.69]; P = 0.022), Δ platelets (OR = 0.95 [0.90–0.99]; P = 0.029), Δ C-reactive protein (CRP) (OR = 1.09 [1.01, 1.18]; P = 0.037), and Δ lactate dehydrogenase (LDH) (OR = 1.03 [1.01, 1.06]; P = 0.007) correlated with an increased risk of death. The potential risk factors of old age, high baseline D-dimer, and dynamic co-variates of fibrinogen, platelets, CRP, and LDH could help clinicians to identify and treat subjects with poor prognosis.


Lack of maternal–fetal SARS-CoV-2 transmission


title: Etablierung eines fischvirus empfänglichen zellstammes aus Hypophysen des Karpfens (Cyprinus carpio L.)

text: Abstract A new continous cell strain (CaPi) was established from normal pituitary tissue of carp, Cyprinus carpio L. Cells of a fractionated dispersion (0.25% trypsin-PBS, 10°C) of pituitaries formed monolayer (fibroblast- and epithelial-like-cells) at 25°C using Eagle's minimal essential medium (MEM) supplemented with 10% fetal calf serum and non essential amino acids. The continous cell strain, designated CaPi, was obtained by an enzymatical selection of epitheloid cells from the monolayer of the primary pituitary cell culture. This culture has been subcultered 70 times over a period of 24 months. CaPi-cells multiply over a temperature range of 15–35°C with an optimum growth temperature of 30°C at a seeding density of 1.7 × 106 cells/ml. Chromosome analysis indicates the cells are heteroploid and show modal numbers of 47 chromosomes. The CaPi cell line is susceptible to fishviruses (VHSV, PFR, SVCV) producing cytopathic effects (CPE). However, IPNV replicates without visible cell alterations.


The Use of Nonsteroidal Anti-inflammatory Drugs in Urological Practice in the COVID-19 Era: Is “Safe Better than Sorry”?


title: Multiple sclerosis

text: Abstract Multiple sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity. It is believed to be autoimmune in nature. The cause is unknown; both genetic and environmental factors have been implicated in the pathogenesis. MS generally presents with the acute or subacute onset of neurologic abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a neurologic examination and laboratory tests. These tests may include magnetic resonance imaging of the head and spine, lumbar puncture, and evoked potentials. Treatment is based on general supportive care, the use of corticosteroids for relapses, and symptomatic management of ongoing problems. The frequency of relapses can be reduced with interferon-β (Betaseron). Copolymer 1 and interferon-β la are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of relapses in relapsing-remitting MS. Treatment of chronic progression is often attempted with immunosuppressive agents such as corticosteroids, azathioprine, and cyclophosphamide. Use of other agents is being investigated.


title: Effect of avian influenza A H5N1 infection on the expression of microRNA-141 in human respiratory epithelial cells

text: BACKGROUND: Avian influenza remains a serious threat to human health. The consequence of human infection varies markedly among different subtypes of avian influenza viruses. In addition to viral factors, the difference in host cellular response is likely to play a critical role. This study aims at elucidating how avian influenza infection perturbs the host’s miRNA regulatory pathways that may lead to adverse pathological events, such as cytokine storm, using the miRNA microarray approach. RESULTS: The results showed that dysregulation of miRNA expression was mainly observed in highly pathogenic avian influenza A H5N1 infection. We found that miR-21*, miR-100*, miR-141, miR-574-3p, miR-1274a and miR1274b were differentially expressed in response to influenza A virus infection. Interestingly, we demonstrated that miR-141, which was more highly induced by H5N1 than by H1N1 (p < 0.05), had an ability to suppress the expression of a cytokine - transforming growth factor (TGF)-β2. This was supported by the observation that the inhibitory effect could be reversed by antagomiR-141. CONCLUSIONS: Since TGF-β2 is an important cytokine that can act as both an immunosuppressive agent and a potent proinflammatory molecule through its ability to attract and regulate inflammatory molecules, and previous report showed that only seasonal influenza H1N1 (but not the other avian influenza subtypes) could induce a persistent expression of TGF-β2, we speculate that the modulation of TGF-β2 expression by different influenza subtypes via miR-141 might be a critical step for determining the outcome of either normal or excessive inflammation progression.


title: SARS‐CoV‐2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability

text: The emergence of SARS‐CoV‐2 has resulted in nearly 1,280,000 infections and 73,000 deaths globally so far. This novel virus acquired the ability to infect human cells using the SARS‐CoV cell receptor hACE2. Because of this, it is essential to improve our understanding of the evolutionary dynamics surrounding the SARS‐CoV‐2 hACE2 interaction. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict whether these genomic regions are under directional or purifying selection between divergent viral lineages, at various scales of relatedness. With this analysis, we determine a region inside the receptor‐binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor ACE2. Next, to gain further insights into factors associated with recognition of the human host receptor, we performed modeling studies of five different betacoronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of SARS‐CoV‐2 infections. We also propose that a glycine residue at the receptor‐binding domain of the spike glycoprotein can have a critical role in permitting bat SARS‐related coronaviruses to infect human cells.


title: Dataset of seismic ambient vibrations from the quaternary Norcia basin (central Italy)

text: Central Italy was affected by a long seismic sequence in 2016 and 2017, characterized by five main-shocks with Mw>5.0. The Mw 6.5 mainshock occurred on 30 October 2016 close to the town of Norcia, located in the intra-Apennine Norcia basin. Different degrees of damages were observed during this seismic crisis, caused by a variable seismic shaking. This was also due to important 1D and 2D variation of Quaternary fluvio-lacustrine sediments infilling the basin. Following such considerations, a new geophysical dataset of seismic vibration measurements was acquired in the study area during the period April 2017–November 2019. We collected mainly single-seismic station noise data, to infer the distribution of resonance frequency (f(0)) of the basin. A total of 60 sites were measured to cover the entire extension in the basin. We deployed seismometers along three transects of a total length of 21 km, mostly along the main structural directions of the basin (i.e. NNW-SSE and NE-SW). Two 2D arrays of seismic stations with a elicoidal-shaped geometry, and a set of MASW active data were also acquired in the northern sector of the basin, in order to better constrain the seismic velocity of the sedimentary infilling. These new records have been integrated with available geological information in order to reconstruct the deep structure of the basin, as discussed in the research paper by [2]. The entire dataset used in [2] is here provided, together with 7 additional records recovered for the basin (i.e. N54-N60) and ancillary open-source geospatial data. The dataset can be used for different purposes: specific research on the Norcia basin, comparative studies on similar areas around the world, development of new data modeling and testing of new analysis software, and as a training dataset for machine learning applications.


title: Potential impact of the COVID-19 pandemic on HIV, tuberculosis, and malaria in low-income and middle-income countries: a modelling study

text: BACKGROUND: COVID-19 has the potential to cause substantial disruptions to health services, due to cases overburdening the health system or response measures limiting usual programmatic activities. We aimed to quantify the extent to which disruptions to services for HIV, tuberculosis, and malaria in low-income and middle-income countries with high burdens of these diseases could lead to additional loss of life over the next 5 years. METHODS: Assuming a basic reproduction number of 3·0, we constructed four scenarios for possible responses to the COVID-19 pandemic: no action, mitigation for 6 months, suppression for 2 months, or suppression for 1 year. We used established transmission models of HIV, tuberculosis, and malaria to estimate the additional impact on health that could be caused in selected settings, either due to COVID-19 interventions limiting activities, or due to the high demand on the health system due to the COVID-19 pandemic. FINDINGS: In high-burden settings, deaths due to HIV, tuberculosis, and malaria over 5 years could increase by up to 10%, 20%, and 36%, respectively, compared with if there was no COVID-19 pandemic. The greatest impact on HIV was estimated to be from interruption to antiretroviral therapy, which could occur during a period of high health system demand. For tuberculosis, the greatest impact would be from reductions in timely diagnosis and treatment of new cases, which could result from any prolonged period of COVID-19 suppression interventions. The greatest impact on malaria burden could be as a result of interruption of planned net campaigns. These disruptions could lead to a loss of life-years over 5 years that is of the same order of magnitude as the direct impact from COVID-19 in places with a high burden of malaria and large HIV and tuberculosis epidemics. INTERPRETATION: Maintaining the most critical prevention activities and health-care services for HIV, tuberculosis, and malaria could substantially reduce the overall impact of the COVID-19 pandemic. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development, and Medical Research Council.


title: Mammalian Two-Hybrid Assay for Detecting Protein-Protein Interactions in Vivo

text: The mammalian two-hybrid system is a very powerful tool to investigate protein-protein interactions in terms of functional domains and identify potential binding ligands and partners of a protein. Compared with the yeast two-hybrid system, the mammalian two-hybrid system provides the milieu for the bona fide posttranslational modifications and localizations of most eukaryotic proteins and, therefore, should be a better choice to study proteins of mammalian origin. This chapter depicts the detailed experimental procedures adapted by various laboratories. Researchers with experience in molecular biology could modify the procedures according to their own needs, that is, the choice of restriction sites in the cloning process. The reference list could be of use to researchers who wish to understand more of the system and explore its wider applications.


title: Genetic evolution and tropism of transmissible gastroenteritis coronaviruses

text: Abstract Transmissible gastroenteritis virus (TGEV) is an enteropathogenic coronavirus isolated for the first time in 1946. Nonenteropathogenic porcine respiratory coronaviruses (PRCVs) have been derived from TGEV. The genetic relationship among six European PRCVs and five coronaviruses of the TGEV antigenic cluster has been determined based on their RNA sequences. The S protein of six PRCVs have an identical deletion of 224 amino acids starting at position 21. The deleted area includes the antigenic sites C and B of TGEV S glycoprotein. Interestingly, two viruses (NEB72 and TOY56) with respiratory tropism have S proteins with a size similar to the enteric viruses. NEB72 and TOY56 viruses have in the S protein 2 and 15 specific amino acid differences with the enteric viruses. Four of the residues changed (aa 219 of NEB72 isolate and as 92, 94, and 218 of TOY56) are located within the deletion present in the PRCVs and may be involved in the receptor binding site (RBS) conferring enteric tropism to TGEVs. A second RBS used by the virus to infect ST cells might be located in a conserved area between sites A and D of the S glycoprotein, since monoclonal antibodies specific for these sites inhibit the binding of the virus to ST cells. An evolutionary tree relating 13 enteric and respiratory isolates has been proposed. According to this tree, a main virus lineage evolved from a recent progenitor virus which was circulating around 1941. From this, secondary lineages originated PUR46, NEB72, TOY56, MIL65, BR170, and the PRCVs, in this order. Least squares estimation of the origin of TGEV-related coronaviruses showed a significant constancy in the fixation of mutations with time, that is, the existence of a well-defined molecular clock. A mutation fixation rate of 7 ± 2 × 10−4 nucleotide substitutions per site and per year was calculated for TGEV-related viruses. This rate falls in the range reported for other RNA viruses. Point mutations and probably recombination events have occurred during TGEV evolution.


title: Bat and Lyssavirus Exposure among Humans in Area that Celebrates Bat Festival, Nigeria, 2010 and 2013

text: Using questionnaires and serologic testing, we evaluated bat and lyssavirus exposure among persons in an area of Nigeria that celebrates a bat festival. Bats from festival caves underwent serologic testing for phylogroup II lyssaviruses (Lagos bat virus, Shimoni bat virus, Mokola virus). The enrolled households consisted of 2,112 persons, among whom 213 (10%) were reported to have ever had bat contact (having touched a bat, having been bitten by a bat, or having been scratched by a bat) and 52 (2%) to have ever been bitten by a bat. Of 203 participants with bat contact, 3 (1%) had received rabies vaccination. No participant had neutralizing antibodies to phylogroup II lyssaviruses, but >50% of bats had neutralizing antibodies to these lyssaviruses. Even though we found no evidence of phylogroup II lyssavirus exposure among humans, persons interacting with bats in the area could benefit from practicing bat-related health precautions.


title: Magnetic particles for the separation and purification of nucleic acids

text: Nucleic acid separation is an increasingly important tool for molecular biology. Before modern technologies could be used, nucleic acid separation had been a time- and work-consuming process based on several extraction and centrifugation steps, often limited by small yields and low purities of the separation products, and not suited for automation and up-scaling. During the last few years, specifically functionalised magnetic particles were developed. Together with an appropriate buffer system, they allow for the quick and efficient purification directly after their extraction from crude cell extracts. Centrifugation steps were avoided. In addition, the new approach provided for an easy automation of the entire process and the isolation of nucleic acids from larger sample volumes. This review describes traditional methods and methods based on magnetic particles for nucleic acid purification. The synthesis of a variety of magnetic particles is presented in more detail. Various suppliers of magnetic particles for nucleic acid separation as well as suppliers offering particle-based kits for a variety of different sample materials are listed. Furthermore, commercially available manual magnetic separators and automated systems for magnetic particle handling and liquid handling are mentioned.


title: Ferroquine and its derivatives: New generation of antimalarial agents

text: Malaria has been teasing human populations from a long time. Presently, several classes of antimalarial drugs are available in market, but the issues of toxicity, lower efficacy and the resistance by malarial parasites have decreased their overall therapeutic indices. Thus, the search for new promising antimalarials continues, however, the battle against malaria is far from over. Ferroquine is a derivative of chloroquine with antimalarial properties. It is the most successful of the chloroquine derivatives. Not only ferroquine, but also its derivatives have shown promising potential as antimalarials of clinical interest. Presently, much research is dedicated to the development of ferroquine derivatives as safe alternatives to antimalarial chemotherapy. The present article describes the structural, chemical and biological features of ferroquine. Several classes of ferroquine derivatives including hydroxyferroquines, trioxaferroquines, chloroquine-bridged ferrocenophanes, thiosemicarbazone derivatives, ferrocene dual conjugates, 4-N-substituted derivatives, and others have been discussed. Besides, the mechanism of action of ferroquine has been discussed. A careful observation has been made into pharmacologically significant ferroquine derivatives with better or equal therapeutic effects to that of chloroquine and ferroquine. A brief discussion of the toxicities of ferroquine derivatives has been made. Finally, efforts have been made to discuss the current challenges and future perspectives of ferroquine-based antimalarial drug development.


title: Potential role of viruses in neurodegeneration

text: Viruses have the capacity to induce alterations and degenerations of neurons by different direct and indirect mechanisms. In the review, we have focused on some examples that may provide new avenues for treatment or altering the course of infections, i.e., antibodies to fusogenic virus membrane proteins, drugs that interfere with lipid metabolism, calcium channel blockers, immunoregulatory molecules, and, and inhibitors of excitotoxic amino acids. Owing to their selectivity in attack on regions of nervous tissue, governed by viral factors and by routes of invasion, viral receptors or metabolic machineries of infected cells, certain viral infections show similarities in distribution of their resulting lesions in the nervous system to that of the common human neurodegenerative diseases (namely, motor neurons disease, Parkinson’s disease, and Alzheimer’s disease). However, it should be emphasized that no infectious agent has as yet provided a complete animal model for any of these diseases, nor has any infectious agent been linked to them from observations on clinical or postomortem materials.


Italian Physical Therapists’ Response to the Novel COVID-19 Emergency


title: Prediction of respiratory disease and diarrhea in veal calves based on immunoglobulin levels and the serostatus for respiratory pathogens measured at arrival

text: Abstract Failure of passive transfer is a common problem in calves destined for veal production. At present it is unknown whether the risk for respiratory disease (BRD) or neonatal calf diarrhea (NCD) in the veal herd is associated with total immunoglobulin (Ig) and/or on the serostatus for respiratory pathogens measured at arrival. Therefore, the first objective of this prospective longitudinal cohort study was to determine associations between serum protein fractions as determined by routine electrophoresis (total protein, albumin, alpha-1 and -2 globulins, beta-globulins and Ig's) at arrival and BRD and NCD in the first 3 weeks of the production cycle. The second objective was to determine whether the serostatus (seropositive/seronegative) of seven respiratory pathogens (bovine respiratory syncytial virus (BRSV), parainfluenzavirus-3, bovine coronavirus (BCV), bovine herpesvirus-1, bovine viral diarrhea virus, Mannheimia haemolytica and Mycoplasma bovis) of these arrival serum samples could be associated with the risk of having BRD. The third objective was to determine which of the electrophoresis proteins and respiratory serostatuses were associated with average daily gain (ADG) in the study period. The study population consisted of 150 rosé veal calves housed in a single air–space. The study period ended at day 18 post arrival, when BRD incidence was judged to be too high to further postpone a group treatment. A Cox regression model was used to determine the effect of the studied protein fractions and antibodies on the time to BRD and NCD occurrence. The effect of the studied predictors on ADG was determined by linear regression. Calves with Ig levels under 7.5g/L had an increased BRD hazard (hazard ratio (HR)=1.9 (95% confidence interval (CI)=1.2–3.0)). NCD was only positively associated with the alpha-2 globulin concentration. Calves with a negative serostatus for BCV (HR=1.7 (95% CI=1.0–2.8)) or BRSV (HR=2.0 (95% CI=1.0–3.9)) had an increased BRD hazard. Average daily gain (ADG) was 0.242kg/day (SD=0.142) and was not related to the occurrence of BRD or NCD. Calves with Ig's below 7.5g/L and with increased levels of alpha-2 globulins showed a decrease in ADG. This study showed the importance of providing sufficient colostrum to veal calves and the potential benefit of the presence of BCV and BRSV antibodies at arrival to reduce the BRD hazard in the first 3 weeks.


title: Internet Hospitals Help Prevent and Control the Epidemic of COVID-19 in China: Multicenter User Profiling Study

text: BACKGROUND: During the spread of the novel coronavirus disease (COVID-19), internet hospitals in China were engaged with epidemic prevention and control, offering epidemic-related online services and medical support to the public. OBJECTIVE: The aim of this study is to explore the role of internet hospitals during the prevention and control of the COVID-19 outbreak in China. METHODS: Online epidemic-related consultations from multicenter internet hospitals in China during the COVID-19 epidemic were collected. The counselees were described and classified into seven type groups. Symptoms were recorded and compared with reported patients with COVID-19. Hypochondriacal suspicion and offline visit motivation were detected within each counselees’ group to evaluate the social panic of the epidemic along with the consequent medical-seeking behaviors. The counselees’ motivation and the doctors’ recommendation for an offline visit were compared. Risk factors affecting the counselees’ tendency of hypochondriacal suspicion and offline visit motivation were explored by logistic regression models. The epidemic prevention and control measures based on internet hospitals were listed, and the corresponding effects were discussed. RESULTS: A total of 4913 consultations were enrolled for analysis with the median age of the counselees at 28 years (IQR 22-33 years). There were 104 (2.12%) healthy counselees, 147 (2.99%) hypochondriacal counselees, 34 (0.69%) exposed counselees, 853 (17.36%) mildly suspicious counselees, 42 (0.85%) moderately suspicious counselees, 3550 (72.26%) highly suspicious counselees, and 183 (3.72%) severely suspicious counselees. A total of 94.20% (n=4628) of counselees had epidemic-related symptoms with a distribution similar to those of COVID-19. The hypochondriacal suspicion (n=2167, 44.11%) was common. The counselees’ motivation and the doctors’ recommendation for offline visits were inconsistent (P<.001) with a Cohen kappa score of 0.039, indicating improper medical-seeking behaviors. Adult counselees (odds ratio [OR]=1.816, P<.001) with epidemiological exposure (OR 7.568, P<.001), shortness of breath (OR 1.440, P=.001), diarrhea (OR 1.272, P=.04), and unrelated symptoms (OR 1.509, P<.001) were more likely to have hypochondriacal suspicion. Counselees with severe illnesses (OR 2.303, P<.001), fever (OR 1.660, P<.001), epidemiological exposure history (OR 1.440, P=.01), and hypochondriacal suspicion (OR 4.826, P<.001) were more likely to attempt an offline visit. Reattending counselees (OR 0.545, P=.002) were less motivated to go to the offline clinic. CONCLUSIONS: Internet hospitals can serve different types of epidemic counselees, offer essential medical supports to the public during the COVID-19 outbreak, reduce the social panic, promote social distancing, enhance the public’s ability of self-protection, correct improper medical-seeking behaviors, reduce the chance of nosocomial cross-infection, and facilitate epidemiological screening, thus, playing an important role on preventing and controlling COVID-19.


title: Colostrum Management for Dairy Calves

text: Colostrum management is the single most important management factor in determining calf health and survival. Unfortunately, a significant proportion of North American dairy calves suffer from failure of passive transfer of antibodies from colostrum, contributing to excessively high preweaning mortality rates and other short- and long-term losses associated with animal health, welfare, and productivity. A successful colostrum management program requires producers to consistently provide calves with a sufficient volume of clean, high-quality colostrum within the first few hours of life. This article reviews the process of colostrogenesis and discusses important components of colostrum. The key components of delivering and monitoring a successful colostrum management program are discussed.


title: The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals

text: The global outbreak of coronavirus disease (COVID-19) has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, post-acute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with COVID-19. Clinicians across the nation’s rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands, and the strategies to meet the needs of this population. The complications from COVID-19 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting, and at home through ongoing therapy either in-person or via telehealth.


Highlights of the issue 5, 2020


title: Upper Respiratory Infections

text: Upper respiratory infections (URIs) are infections of the mouth, nose, throat, larynx (voice box), and trachea (windpipe). This article outlines the epidemiology, etiology, diagnosis, and management of URIs, including nasopharyngitis (common cold), sinusitis, pharyngitis, laryngitis, and laryngotracheitis.


title: Anti-RAS drugs and SARS-CoV-2 infection

text: • There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. • The level of ACE2 expression is not completely related with the risk of COVID-19 infection. • There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. • It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.


title: Discovery, synthesis, and optimization of an N-alkoxy indolylacetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root

text: From an aqueous decoction of the traditional Chinese medicine “ban lan gen” (the Isatis indigotica root), an antiviral natural product CI - 39 was isolated as an NNRTI (non-nucleoside reverse transcriptase inhibitor) (EC(50) = 3.40 μM). Its novel structure was determined as methyl (1-methoxy-1H-indol-3-yl)acetamidobenzoate by spectroscopic data and confirmed by single crystal X-ray diffraction. Through synthesis and structure-activity relationship (SAR) investigation of CI - 39 and 57 new derivatives (24 with EC(50) values of 0.06–8.55 μM), two optimized derivatives 10f and 10i (EC(50): 0.06 μM and 0.06 μM) having activity comparable to that of NVP (EC(50) = 0.03 μM) were obtained. Further evaluation verified that 10f and 10i were RT DNA polymerase inhibitors and exhibited better activities and drug resistance folds compared to NVP against seven NNRTI-resistant strains carrying different mutations. Especially, 10i (EC(50) = 0.43 μM) was more active to the L100I/K103N double-mutant strain as compared to both NVP (EC(50) = 0.76 μM) and EFV (EC(50) = 1.08 μM). The molecular docking demonstrated a possible binding pattern between 10i and RT and revealed activity mechanism of 10i against the NNRTI-resistant strains.


title: Systematic literature review on novel corona virus SARS-CoV-2: a threat to human era

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the seventh-generation coronavirus family causing viral pandemic coronavirus disease (COVID-19) across globe affecting millions of people. The objectives of this study are to (1) identify the major research themes in COVID-19 literature, (2) determine the origin, symptoms and modes of transmission of COVID, (3) recommend the intervention and mitigation strategies adopted by the Governments globally against the spread of COVID-19 and the traumatization among the public? and (4) study the possible drugs/treatment plans against COVID-19. A systematic literature review and comprehensive analysis of 38 research articles on COVID-19 are conducted. An integrated Research focus parallel-ship network and keyword co-occurrence analysis are carried out to visualize the three research concepts in COVID-19 literature. Some of our observations include: (1) as SARS-CoV-2’s RNA matches ~ 96% to SARS-CoV, it is assumed to be transmitted from the bats. (2) The common symptoms are high fever, dry cough, fatigue, sputum production, shortness of breath, diarrhoea etc. (3) A lockdown across 180 affected counties for more than a month with social-distancing and the precautions taken in SARS and MERS are recommended by the Governments. (4) Researchers’ claim that nutrition and immunity enhancers and treatment plans such as arbidol, lopinavir/ritonavir, convalescent plasma and mesenchymal stem cells and drugs including remdesivir, hydroxychloroquine, azithromycin and favipiravir are effective against COVID-19. This complied report serves as guide to help the administrators, researchers and the medical officers to adopt recommended intervention strategies and the optimal treatment/drug against COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13337-020-00604-z) contains supplementary material, which is available to authorized users.


title: Adaptive memory and evolution of the human naturalistic mind: Insights from the use of medicinal plants

text: Throughout evolutionary history, humans have been exposed to a wide variety of diseases, some of which have serious and even lethal consequences. Memorizing medicinal plants for the treatment of serious diseases likely maximized the chances of survival and reproduction and was instrumental in the evolutionary success of our species. In the present study, we used the idea of adaptive memory to understand whether human memory evolved to recall information about medicinal plants for the treatment of serious diseases. We considered plant-disease pairs of words as units of information available in a medical system based on the use of medicinal plants. The pairs included in the categories of chronic infectious diseases and transmissible infectious diseases were considered to be of higher adaptive value, whereas those included in the category of common conditions were considered to be of lower adaptive value. Pairs grouped into the category of emerging and reemerging diseases were employed to investigate conformity bias; pairs belonging to the category esthetic uses were considered to be of little adaptive relevance and utilized as an experimental control. Our results revealed that plant-disease pairs associated with the category of common conditions, considered by us to be of lower severity and less adaptive relevance for humans, were better remembered and retained in the participants' memory. We believe that prior experience with common conditions and the frequency of these conditions in the population may have intensified the ability to remember the plant-disease pairs associated with this group of diseases.


title: Potential role of memantine in the prevention and treatment of COVID-19: its antagonism of nicotinic acetylcholine receptors (nAChR) and beyond

text: Memantine, as an antagonist of α7-nAChR and NMDA receptors may decrease ACE2 receptors expression and reduce oxidative stress and inflammation. Hence, memantine may potentially reduce SARS-CoV-2 virulence.


Challenges and countermeasures for organ donation during the SARS-CoV-2 epidemic: the experience of Sichuan Provincial People’s Hospital


title: Human Interaction Smart Subsystem—Extending Speech-Based Human-Robot Interaction Systems with an Implementation of External Smart Sensors

text: This paper presents a more detailed concept of Human-Robot Interaction systems architecture. One of the main differences between the proposed architecture and other ones is the methodology of information acquisition regarding the robot’s interlocutor. In order to obtain as much information as possible before the actual interaction took place, a custom Internet-of-Things-based sensor subsystems connected to Smart Infrastructure was designed and implemented, in order to support the interlocutor identification and acquisition of initial interaction parameters. The Artificial Intelligence interaction framework of the developed robotic system (including humanoid Pepper with its sensors and actuators, additional local, remote and cloud computing services) is being extended with the use of custom external subsystems for additional knowledge acquisition: device-based human identification, visual identification and audio-based interlocutor localization subsystems. These subsystems were deeply introduced and evaluated in this paper, presenting the benefits of integrating them into the robotic interaction system. In this paper a more detailed analysis of one of the external subsystems—Bluetooth Human Identification Smart Subsystem—was also included. The idea, use case, and a prototype, integration of elements of Smart Infrastructure systems and the prototype implementation were performed in a small front office of the Weegree company as a decent test-bed application area.


title: Association between Australian Hajj Pilgrims’ awareness of MERS-CoV, and their compliance with preventive measures and exposure to camels

text: Through a prospective cohort study the relationship between travellers’ awareness of MERS-CoV, and compliance with preventive measures and exposure to camels was evaluated among Australian Hajj pilgrims who attended Hajj in 2015. Only 28% of Australian Hajj pilgrims were aware of MERS-CoV in Saudi Arabia. Those who were aware of MERS-CoV were more likely to receive recommended vaccines [odds ratio (OR) 3.1, 95% confidence interval (CI): 1.5–5.9, P < 0.01], but there was no significant difference in avoiding camels or their raw products during Hajj between those who were aware of MERS-CoV and those who were not (OR 1.2, 95% CI: 0.3–5.2, P = 0.7). Hajj pilgrims’ awareness is reflected in some of their practices but not in all.


title: Infectious causes of reproductive loss in camelids

text: Reproductive losses in camelids are due to infertility, pregnancy loss, udder diseases and neonatal mortality caused by a variety of infectious diseases. Uterine infection and abortion represent the major complaint in camelid veterinary practice. The major infectious organisms in endometritis and metritis are E. coli and Streptococcus equi subspecies zooepidemicus. Abortion rates due to infectious diseases vary from 10% to more than 70% in some areas. Leptospirosis, toxoplasmosis and chlamydiosis have been diagnosed as the major causes of abortion in llamas and alpacas. In camels, brucellosis and trypanosomiasis represent the major causes of infectious abortion in the Middle East and Africa. Mastitis is rare in South American camelids. The prevalence of subclinical udder infection in camels can reach very high proportions in dairy camels. Udder infections are primarily due to Streptococcus agalactiae and Staphylococcus aureus. Neonatal mortality is primarily due to diarrhea following failure of passive transfer and exposure to E. coli, rotavirus, coronavirus, Coccidia and Salmonella. This paper reviews the etio-pathogenesis of these causes of reproductive losses, as well as the major risk factors and strategies to prevent their occurrence.


title: Control of a hospital-wide vancomycin-resistant Enterococci outbreak

text: BACKGROUND: To analyze control measures used to eradicate a large vancomycin-resistant Enterococci (VRE) outbreak in a nonendemic 1600-bed tertiary care institution. METHODS: In mid-March 2005, VRE Van B was isolated from 2 clinical samples from different wards. Despite such measures as screening patients sharing rooms with index cases and isolating VRE patients, 43 isolates from different wards were detected by the end of March 2005. To eradicate a hospital-wide outbreak, a coordinated strategy between March and June 2005 comprised (1) formation of a VRE task force, (2) hospital-wide screening, (3) isolation of carriers, (4) physical segregation of contacts, (5) surveillance of high-risk groups, (6) increased cleaning, (7) electronic tagging of VRE status, and (8) education and audits. This is a retrospective study of this multipronged approach to containing VRE. The adequacy of rectal swab sampling for VRE was assessed in a substudy of 111 patients. The prevalence of methicillin-resistant Staphylococcus aureus (MRSA)/VRE co-colonization or co-infection also was determined. RESULTS: A total of 19,574 contacts were identified. Between April and June 2005, 5095 patients were screened, yielding 104 VRE carriers, 54 of whom (52%) were detected in the first 2 weeks of hospital-wide screening. The initial positive yield of 11.4% of persons actively screened declined to 4.2% by the end of June 2005. Pulsed-field typing revealed 1 major clone and several minor clones among the 151 total VRE cases, including 4 clinical cases. Hospital-wide physical segregation of contacts from other patients was difficult to achieve in communal wards. Co-colonization or co-infection with MRSA, which was present in 52 of 151 cases (34%) and the indefinite electronic tagging of positive VRE status strained limited isolation beds. Analysis of 2 fecal or rectal specimens collected 1 day apart may detect at least 83% of VRE carriers. CONCLUSION: A multipronged strategy orchestrated by a central task force curbed but could not eradicate VRE. Control measures were confounded by hospital infrastructure and high MRSA endemicity.


title: Experience with intravenous ribavirin in the treatment of hemorrhagic fever with renal syndrome in Korea

text: Abstract Results of a clinical study using intravenous (IV) ribavirin for treating Department of Defense personnel with hemorrhagic fever with renal syndrome (HFRS) acquired in Korea from 1987 to 2005 were reviewed to determine the clinical course of HFRS treated with IV ribavirin. A total of 38 individuals enrolled in the study had subsequent serological confirmation of HFRS. Four of the 38 individuals received three or fewer doses of ribavirin and were excluded from treatment analysis. Of the remaining 34 individuals, oliguria was present in one individual at treatment initiation; none of the remaining 33 subjects developed oliguria or required dialysis. The mean peak serum creatinine was 3.46mg/dl and occurred on day 2 of ribavirin therapy. Both the peak serum creatinine and the onset of polyuria occurred on mean day 6.8 of illness. Reversible hemolytic anemia was the main adverse event of ribavirin, with a ≥25% decrease in hematocrit observed in 26/34 (76.5%) individuals. While inability to adjust for all baseline variables prevents comparison to historical cohorts in Korea where oliguria has been reported in 39–69% cases and dialysis required in approximately 40% HFRS cases caused by Hantaan virus, the occurrence of 3% oliguria and 0% dialysis requirement in the treatment cohort is supportive of a previous placebo-controlled HFRS trial in China where IV ribavirin given early resulted in decreased occurrence of oliguria and decreased severity of renal insufficiency.


title: Respiratory function and pulmonary lesions in pigs infected with porcine reproductive and respiratory syndrome virus

text: Abstract Pulmonary dysfunction was evaluated in pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV, isolate VR-2332) and compared to clinical and pathological findings. Infected pigs developed fever, reduced appetite, respiratory distress and dullness at 9days post-inoculation (dpi). Non-invasive pulmonary function tests using impulse oscillometry and rebreathing of test gases (He, CO) revealed peripheral airway obstruction, reduced lung compliance and reduced lung CO-transfer factor. PRRSV-induced pulmonary dysfunction was most marked at 9–18 dpi and was accompanied by a significantly increased respiratory rate and decreased tidal volume. Expiration was affected more than inspiration. On histopathological examination, multifocal areas of interstitial pneumonia (more severe and extensive at 10 dpi than 21 dpi) were identified as a possible structural basis for reduced lung compliance and gas exchange disturbances.


Clinical and Histopathological study of skin dermatoses in patients affected by COVID-19 infection in the Northern part of Italy


title: Retrospective investigation and evolutionary analysis of a novel porcine deltacoronavirus strain detected in Thailand from 2008 to 2015

text: Porcine deltacoronavirus (PDCoV) in Thailand was first detected in 2015. We performed a retrospective investigation of the presence of PDCoV in intestinal samples collected from piglets with diarrhea in Thailand from 2008 to 2015 using RT-PCR. PDCoV was found to be present as early as February 2013. Phylogenetic analysis demonstrated that all PDCoV variants from Thailand differ from those from other countries and belong to a novel group of PDCoV that is separate from the US and Chinese PDCoV variants. Evolutionary analysis suggested that the Thai PDCoV isolates probably diverged from a different ancestor from that of the Chinese and US PDCoV isolates and that this separation occurred after 1994. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00705-017-3331-3) contains supplementary material, which is available to authorized users.


title: Molecular epidemiology of infectious bronchitis virus in Poland from 1980 to 2017

text: Abstract The presence of infectious bronchitis virus (IBV) was identified for the first time in the poultry population in Poland at the end of the 1960s. From this time a few waves of epidemics caused by different IBV variants spread across the country. In order to gain more insight into the molecular epidemiology of IBV in Poland, in the present study the S1 coding region of 34 IBV isolates and nearly whole genome of 10 strains collected over a period of 38 years was characterized. Phylogenetic analysis showed that these strains belonged to five recently established IBV lineages: GI-1, GI-12, GI-13, GI-19 and GI-23. Additionally, two strains from 1989 and 1997 formed a separate branch of the phylogenetic tree categorized as unique early Polish variants, and one strain was revealed to be the recombinant of these and GI-1 lineage viruses. Irrespective of year of isolation and S1-dependent genotype, the genome sequences of Polish IBV strains showed the presence of six genes and 13 ORFs: 5′UTR-1a-1b-S-3a-3b-E-M-4b-4c-5a-5b-N-6b-3′UTR, however their individual genes and putative proteins had different lengths. The phylogenetic analyses performed on the genome of ten Polish IBV strains revealed that they cluster into different groups. The Polish GI-1, GI-19 and GI-23 strains cluster with other similar viruses of these lineages, with the exception of the two strains from 1989 and 1997 which are different. It seems that in Poland in the 1980s and 1990s IBV strains with a unique genome backbone circulated in the field, which were then replaced by other strains belonging to other IBV lineages with a genome backbone specific to these lineages. The recombination analysis showed that some Polish strains resulted from a recombination event involving different IBV lineages, most frequently GI-13 and GI-19.


title: Human coronavirus gene expression in the brains of multiple sclerosis patients

text: Abstract Total RNA extracted from both white and gray matter of brain tissue from multiple sclerosis (MS) patients and controls was analyzed using a reverse transcription-polymerase chain reaction for the presence of the nucleic acid of human coronavirus (HCV) 229E and OC43, the two strains characterized to date and associated with respiratory infections. HCV-229E viral RNA was detectable in the central nervous system tissue of 4 of 11 MS patients and in none of 6 neurological and 5 normal controls. No HCV-OC43 nucleic acid was detected in any of the specimens. These results suggest a neurotropism on the part of the 229E strain of human coronavirus and underline the importance of further studies on its tissue distribution. The fact that it was detected only in tissue from MS patients illustrates the need for continued studies on the possible role of coronaviruses in the etiology of MS.


title: Processing of the SARS-CoV pp1a/ab nsp7–10 region

text: Severe acute respiratory syndrome coronavirus is the causative agent of a respiratory disease with a high case fatality rate. During the formation of the coronaviral replication/transcription complex, essential steps include processing of the conserved polyprotein nsp7–10 region by the main protease M(pro) and subsequent complex formation of the released nsp's. Here, we analyzed processing of the coronavirus nsp7–10 region using native mass spectrometry showing consumption of substrate, rise and fall of intermediate products and complexation. Importantly, there is a clear order of cleavage efficiencies, which is influenced by the polyprotein tertiary structure. Furthermore, the predominant product is an nsp7+8(2 : 2) hetero-tetramer with nsp8 scaffold. In conclusion, native MS, opposed to other methods, can expose the processing dynamics of viral polyproteins and the landscape of protein interactions in one set of experiments. Thereby, new insights into protein interactions, essential for generation of viral progeny, were provided, with relevance for development of antivirals.


title: Viral Respiratory Tract Infections in the Neonatal Intensive Care Unit: The VIRIoN-I Study

text: Objective To determine the frequency of respiratory viral infections among infants who were evaluated for late-onset sepsis in the neonatal intensive care units (NICUs) of Parkland Memorial Hospital, Dallas, Texas; and Women & Infants Hospital, Providence, Rhode Island. Study design Prospective cohort study conducted from January 15, 2012 to January 31, 2013. Infants in the NICU were enrolled if they were inborn, had never been discharged home, and were evaluated for sepsis (at >72 hours of age) and antibiotic therapy was initiated. Infants had a nasopharyngeal specimen collected for detection of respiratory viruses by multiplex polymerase chain reaction within 72 hours of the initiation of antibiotic therapy. Their medical records were reviewed for demographic, clinical, radiographic, and laboratory data until NICU discharge. Results During the 13-month study, 8 of 100 infants, or 8 (6%) of the 135 sepsis evaluations, had a respiratory virus detected by polymerase chain reaction (2, enterovirus/rhinovirus; 2, rhinovirus; 2, coronaviruses; and 2, parainfluenza-3 virus). By bivariate analysis, the infants with viral detection were older (41 vs 11 days; P = .007), exposed to individuals with respiratory tract viral symptoms (37% vs 2%; P = .003), tested for respiratory viruses by provider (75% vs 11%; P < .001), and had lower total neutrophil counts (P = .02). In multivariate regression analysis, the best predictor of viral infection was the caregivers' clinical suspicion of viral infection (P = .006). Conclusions A total of 8% of infants, or 6% of all NICU sepsis evaluations, had a respiratory virus detected when evaluated for bacterial sepsis. These findings argue for more respiratory viral testing of infants with suspected sepsis using optimal molecular assays to establish accurate diagnoses, prevent transmission, and inform antibiotic stewardship efforts.


title: Identifying factors and target preventive therapies for Middle East Respiratory Syndrome sucsibtable patients

text: BACKGROUND: Middle East Respiratory Syndrome (MERS) is a respiratory disease caused by a novel coronavirus that was identified in 2012 in Saudi Arabia. It is associated with significant mortality and morbidity. We identified factors associated with the Middle East Respiratory Syndrome-Coronavirus (MERS‐CoV) infection among suspected cases presented with sign and symptoms of upper respiratory infection or exposure to the virus. We also looked at the impact of medication history on virus transmission. METHOD: We included subjects with suspected MERS-CoV infection and confirmed cases of MERS infection. Subjects were excluded if there were any missing data that prevent the final analysis. Descriptive statistics were used to report demographic data. Percentages and frequencies were used to summarize the categorical variables, while means and standard deviations were calculated for continuous variables. Logistic regression was used to assess the risk of MERS-CoV infection among the suspected cases. A value of p < 0.05 was considered statistically significant. RESULTS: A total of 16,189 suspected cases were identified, complete data were analyzed for 3154 to assess factors that are independently associated with MERS-CoV infection. MERS-CoV infection was associated with age (adjusted odds ratio [AOR] = 1.06; 95% CI [1.02–1.098], P-value = 0.004), male gender (AOR = 1.617; 95% CI [1.365–1.77], P-value < 0.001) and diabetes (AOR = 1.68; 95% CI [1.346–1.848], P-value = 0.002. There was no significant association with the other comorbidities. Medication history was not associated with an increase or decrease the likelihood of the infection. CONCLUSIONS: MERS-Cov infection is more common in male, advanced age and diabetes. No medications were associated with an increase or decrease the likelihood of the infection. This is important to focus on screening and detection to this patient population.


title: Proteomic Fingerprints for Potential Application to Early Diagnosis of Severe Acute Respiratory Syndrome

text: Background: Definitive early-stage diagnosis of severe acute respiratory syndrome (SARS) is important despite the number of laboratory tests that have been developed to complement clinical features and epidemiologic data in case definition. Pathologic changes in response to viral infection might be reflected in proteomic patterns in sera of SARS patients. Methods: We developed a mass spectrometric decision tree classification algorithm using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Serum samples were grouped into acute SARS (n = 74; <7 days after onset of fever) and non-SARS [n = 1067; fever and influenza A (n = 203), pneumonia (n = 176); lung cancer (n = 29); and healthy controls (n = 659)] cohorts. Diluted samples were applied to WCX-2 ProteinChip arrays (Ciphergen), and the bound proteins were assessed on a ProteinChip Reader (Model PBS II). Bioinformatic calculations were performed with Biomarker Wizard software 3.1.1 (Ciphergen). Results: The discriminatory classifier with a panel of four biomarkers determined in the training set could precisely detect 36 of 37 (sensitivity, 97.3%) acute SARS and 987 of 993 (specificity, 99.4%) non-SARS samples. More importantly, this classifier accurately distinguished acute SARS from fever and influenza with 100% specificity (187 of 187). Conclusions: This method is suitable for preliminary assessment of SARS and could potentially serve as a useful tool for early diagnosis.


title: Understanding infectious agents from an in silico perspective

text: Knowledge of infectious diseases now emerging from genomic, proteomic, epidemiological and clinical data can provide insights into the mechanisms of immune function, disease pathogenesis and epidemiology. Here, we describe how considerable advances in computational methods of data mining, mathematical modeling in epidemiology and simulation have been used to enhance our understanding of infectious agents and discuss their impact on the discovery of new therapeutics and controlling their spread.


title: Regulatory Consideration on Preparation and Clinical Use of COVID-19 Convalescent Plasma

text: Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease (COVID-19), spreading from Wuhan to worldwide has been emerged since December 2019. Although scientists and researchers have been racing to develop specific therapeutic agents or vaccines against SARS-CoV-2 since the identification of the agent, either a drug or a vaccine has not been approved to treat or to prevent COVID-19 up to date. On the base of historical experiences, Convalescent Plasma (CP), a passive antibody therapy, has been evaluated as a hopeful and potential therapeutic option since the beginning of the COVID-19 outbreak. Immune plasma had been used previously for the treatment of H1N1 influenza virus, SARS-CoV-1 and MERS-CoV epidemics successfully. In this scope competent authorities are responsible to set up certain principles and criteria for the collection and clinical use of COVID-19 Convalescent Plasma (CCP). This document has been prepared to aid both for the convalescent plasma suppliers and the clinicians. The first part encompasses the supply of CCP and the second part lead the clinical use of CCP for the treatment of patients with severe COVID-19 infection. Turkish Ministry of Health developed a guide on collection and clinical use of CCP and created a web-based monitoring system to follow-up the patients treated with convalescent plasma in universal. This follow-up process is thought to be crucial for the creation and development of current and future treatment modalities. This guide would be a pathfinder for clinicians and/or institutions those eager to conduct CCP treatment more effectively.