title: Data-driven modelling and prediction of COVID-19 infection in India and correlation analysis of the virus transmission with socio-economic factors

text: AIMS: The current study attempts to model the COVID-19 outbreak in India, USA, China, Japan, Italy, Iran, Canada and Germany. The interactions of coronavirus transmission with socio-economic factors in India using the multivariate approach were also investigated. METHODS: Actual cumulative infected population data from 15 February to May 15, 2020 was used for determination of parameters of a nested exponential statistical model, which were further employed for the prediction of infection. Correlation and Principal component analysis provided the relationships of coronavirus spread with socio-economic factors of different states of India using the Rstudio software. RESULTS: Cumulative infection and spreadability rate predicted by the model was in good agreement with the actual observed data for all countries (R(2) = 0.985121 to 0.999635, and MD = 1.2–7.76%) except Iran (R(2) = 0.996316, and MD = 18.38%). Currently, the infection rate in India follows an upward trajectory, while other countries show a downward trend. The model claims that India is likely to witness an increased spreading rate of COVID-19 in June and July. Moreover, the flattening of the cumulative infected population is expected to be obtained in October infecting more than 12 lakhs people. Indian states with higher population were more susceptible to virus infection. CONCLUSIONS: A long-term prediction of cumulative cases, spreadability rate, pandemic peak of COVID-19 was made for India. Prediction provided by the model considering most recent data is useful for making appropriate interventions to deal with the rapidly emerging pandemic.


Therapeutic Use of Immunoglobulins


title: Ocular Examination and Corneal Surface Disease in the Ferret

text: This article provides a brief, clinically relevant review of corneal surface disease in the ferret. A description of the ophthalmic examination of the ferret is provided. Stepwise descriptions of the most common ophthalmic abnormalities are provided, along with common rule-outs.


title: Transcriptome-wide shift from photosynthesis and energy metabolism upon endogenous fluid protein depletion in young Nepenthes ampullaria pitchers

text: Carnivorous pitcher plants produce specialised pitcher organs containing secretory glands, which secrete acidic fluids with hydrolytic enzymes for prey digestion and nutrient absorption. The content of pitcher fluids has been the focus of many fluid protein profiling studies. These studies suggest an evolutionary convergence of a conserved group of similar enzymes in diverse families of pitcher plants. A recent study showed that endogenous proteins were replenished in the pitcher fluid, which indicates a feedback mechanism in protein secretion. This poses an interesting question on the physiological effect of plant protein loss. However, there is no study to date that describes the pitcher response to endogenous protein depletion. To address this gap of knowledge, we previously performed a comparative RNA-sequencing experiment of newly opened pitchers (D0) against pitchers after 3 days of opening (D3C) and pitchers with filtered endogenous proteins (>10 kDa) upon pitcher opening (D3L). Nepenthes ampullaria was chosen as a model study species due to their abundance and unique feeding behaviour on leaf litters. The analysis of unigenes with top 1% abundance found protein translation and stress response to be overrepresented in D0, compared to cell wall related, transport, and signalling for D3L. Differentially expressed gene (DEG) analysis identified DEGs with functional enrichment in protein regulation, secondary metabolism, intracellular trafficking, secretion, and vesicular transport. The transcriptomic landscape of the pitcher dramatically shifted towards intracellular transport and defence response at the expense of energy metabolism and photosynthesis upon endogenous protein depletion. This is supported by secretome, transportome, and transcription factor analysis with RT-qPCR validation based on independent samples. This study provides the first glimpse into the molecular responses of pitchers to protein loss with implications to future cost/benefit analysis of carnivorous pitcher plant energetics and resource allocation for adaptation in stochastic environments.


title: Serological survey of SARS‐CoV‐2 for experimental, domestic, companion and wild animals excludes intermediate hosts of 35 different species of animals

text: The pandemic SARS‐CoV‐2 has been reported in 123 countries with more than 5,000 patients died from it. However, the original and intermediate hosts of the virus remain unknown. In this study, 1,914 serum samples from 35 animal species were used for detection of SARS‐CoV‐2‐specific antibodies using double‐antigen sandwich ELISA after validating its specificity and sensitivity. The results showed that no SARS‐CoV‐2‐specific antibodies were detected in above samples which excluded the possibility of 35 animal species as intermediate host for SARS‐CoV‐2. More importantly, companion animals including pet dogs (including one dog the SARS‐CoV‐2 patient kept and two dogs which had close contact with it) and cats, street dogs and cats also showed serological negative to SARS‐CoV‐2, which relieved the public concerns for the pets as SARS‐CoV‐2 carriers.


title: The growth pattern and fuel life cycle analysis of the electricity consumption of Hong Kong

text: As the consumption of electricity increases, air pollutants from power generation increase. In metropolitans such as Hong Kong and other Asian cities, the surge of electricity consumption has been phenomenal over the past decades. This paper presents a historical review about electricity consumption, population, and change in economic structure in Hong Kong. It is hypothesized that the growth of electricity consumption and change in gross domestic product can be modeled by 4-parameter logistic functions. The accuracy of the functions was assessed by Pearson's correlation coefficient, mean absolute percent error, and root mean squared percent error. The paper also applies the life cycle approach to determine carbon dioxide, methane, nitrous oxide, sulfur dioxide, and nitrogen oxide emissions for the electricity consumption of Hong Kong. Monte Carlo simulations were applied to determine the confidence intervals of pollutant emissions. The implications of importing more nuclear power are discussed.


title: Opening up while locking down: how an Irish independent sector mental health service is responding to the COVID-19 crisis

text: The COVID-19 pandemic poses a particular set of challenges for health services. Some of these are common across all services (e.g. strategies to minimise infections; timely testing for patients and staff; and sourcing appropriate personal protective equipment (PPE)) and some are specific to mental health services (e.g. how to access general medical services quickly; how to safely deliver a service that traditionally depends on intensive face to face contact; how to isolate someone who does not wish to do so; and how to source sufficient PPE in the face of competing demands for such equipment). This paper describes how St Patrick’s Mental Health Services (SPMHS) chose to address this unfolding and ever-changing crisis, how it developed its strategy early based on a clear set of objectives and how it adapted (and continues to adapt) to the constantly evolving COVID-19 landscape.


title: International Adoption: Issues in Infectious Diseases

text: International adoptions have become increasingly common in the United States. Children awaiting international adoption and families traveling to adopt these children can be exposed to a variety of infectious diseases. Compared with the United States, foreign countries often have different immunization practices and methods of diagnosing, treating, and monitoring disease. Reporting of medical conditions can also differ from that of the United States. The prevalence of infectious diseases varies from country to country and may or may not be common among adopted children. The transmission of tuberculosis, hepatitis B, and measles from adopted children to family members has been documented. Furthermore, infectious organisms (e.g., intestinal parasites), bacterial pathogens (e.g., Bordetella pertussis and Treponema pallidum), and viruses (e.g., human immunodeficiency virus and hepatitis viruses) may cause clinically significant morbidity and mortality among infected children. Diseases such as severe acute respiratory syndrome or avian influenza have not been reported among international adoptees, but transmission is possible if infection is present. Family members may be infected by others during travel or by their adopted child after returning home. Families preparing to adopt a child from abroad should pay special attention to the infectious diseases they may encounter and to the precautions they should take on returning home.


title: In-hospital evaluation of orthophthalaldehyde as a high level disinfectant for flexible endoscopes

text: Abstract One hundred endoscopes used for bronchoscopy (30), gastroscopy (35) or colonoscopy (35) were studied to determine the efficiency of a new high level disinfectant, orthophthalaldehyde (OPA). Manual cleaning was the method studied since this would be the least effective and thereby provide the greatest challenge to the 0·5% ( w v ) OPA solution. The OPA was convenient and easy to use since it did not have irritating vapours and as it is used directly, does not require dilution. Our study demonstrated that the OPA was stable for up to 14 days despite repeated re-use. The cleaning/ disinfection procedure could achieve a ⩾5 LOG10 reduction in bacterial load. This in-hospital evaluation supports the conclusion that OPA is an effective choice as a high level disinfectant for flexible endoscopes.


title: The impact of the COVID-19 outbreak on the medico-legal and human rights of psychiatric patients

text: The COVID-19 pandemic has raised significant concerns for population mental health and the effective provision of mental health services in the light of increased demands and barriers to service delivery [1]. Particular attention is being directed toward the possible neuropsychiatric sequelae of both COVID-19 and of the stringent societal mitigation steps deployed by national governments, concerns that are informed by historical increases in the incidence of psychotic disorders following influenza pandemics [2]. However, so far there has been scant attention paid to other important areas of psychiatry during COVID-19, including medico-legal aspects and human rights. In this paper, we discuss the legal implications for psychiatry of the COVID-19 pandemic and report a novel situation in which psychiatric patients may experience diminution of their statutory protections. We believe that this represents a paradigm shift in psychiatric care and that the consideration of the fundamental rights of psychiatric patients as “less important” than infection control measures compel mental health professionals to “advocate for … patients and their caregivers” in this time of crisis [1].


title: In situ reverse-transcription loop-mediated isothermal amplification (in situ RT-LAMP) for detection of Japanese encephalitis viral RNA in host cells

text: Abstract Background Clinical diagnosis of Japanese encephalitis is usually difficult due to non-specific signs at the early and acute stages of the infection. Virus isolation from peripheral blood is also not possible because of the short period and low level of transient viremia even in the acute stage of the disease. It is thus urgent to develop a feasible and convenient method for laboratory diagnosis of the infection. Objectives To establish a newly designed molecular approach that can be used to detect intracellular Japanese encephalitis viral RNA in host cells. Study design The method was firstly established and then was carried out to test its efficacy in cultured BHK-21 cells, subsequently in peripheral blood mononuclear cells (PBMCs) isolated from mice that have been inoculated with JE virus suspension. Results In this study, in situ reverse-transcription loop-mediated isothermal amplification (in situ RT-LAMP) was established; which combines merits of recently developed loop-mediated isothermal amplification (LAMP) and in situ reverse-transcriptase polymerase chain reaction (in situ RT-PCR). Conclusions The newly designed method can detect viral RNAs in peripheral blood mononuclear cells (PBMCs) in a short time with high sensitivity and efficiency.


Managing yourself and keeping your family safe: An experience of a COVID positive surgeon


title: Informal motorbike taxi drivers and mobility injustice on Hanoi's streets. Negotiating the curve of a new narrative

text: Abstract The central government of the Socialist Republic of Vietnam and Hanoi's municipal authorities are enthusiastically embracing a series of plans and policies for the capital city to create a sustainable mega-city. This state imaginary privileges ‘modern’ mobilities, championing highways, a bus rapid transport system, and an elevated metro, while so called ‘traditional’ means of moving around the city such as motorbikes, bicycles, or cyclos are being strongly discouraged and increasingly marginalised. For example, Hanoi officials are implementing a step-wise ban on motorbikes from downtown streets by 2030, while the majority of the urban population travels by motorbike, with about five million motorbikes plying the city's streets. While such an approach not only creates mobility injustice for lower socio-economic residents of the city as a whole, it threatens to undermine the livelihoods of thousands of informal motorbike taxi drivers (locally known as xe ôm). In this article I engage with the emerging mobility injustice literature to explore how state discourses regarding urban modernisation are impacting the possibilities for Hanoi's xe ôm drivers to maintain access to city streets and viable livelihoods. These drivers must negotiate emerging and often conflicting state policies, their enforcement, as well as new app-based competitors, all of which challenge the equitable distribution of motility and produce important frictions. Nonetheless, xe ôm drivers draw on their agency and creativity during their daily routines to push back, while also creating new narratives regarding their vital role in maintaining neighbourhood security. We thus see how marginalised individuals are counteracting policies they consider unjust, even when this urban agenda is embedded in a politically socialist context.


title: Viruses and viral proteins

text: For more than 30 years X-ray crystallography has been by far the most powerful approach for determining the structures of viruses and viral proteins at atomic resolution. The information provided by these structures, which covers many important aspects of the viral life cycle such as cell-receptor recognition, viral entry, nucleic acid transfer and genome replication, has extensively enriched our vision of the virus world. Many of the structures available correspond to potential targets for antiviral drugs against important human pathogens. This article provides an overview of the current knowledge of different structural aspects of the above-mentioned processes.


Ethical framework for head and neck endocrine surgery in the COVID‐19 pandemic


title: Novel COVID-19: A Comprehensive Review of Transmission, Manifestation, and Pathogenesis

text: A global outbreak highlights the start of a new decade as a new strain of coronaviruses emerges. Coronavirus disease 2019 (COVID-19), also referred to as Wuhan-Hu-1-CoV - amongst many other names - emerged from the West District of Southern China Seafood Wholesale Market in late December 2019. With the emergence of the new decade, the causative agent of COVID-19 was identified: severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). COVID-19 became declared a global pandemic by the World Health Organization (WHO). COVID-19, currently, is affecting 204 countries and territories and two international conveyances. Initial stages of COVID-19 present with symptoms that mimic the common cold and individuals may be asymptomatic carriers and thus, transmitting the virus to others. COVID-19, like other coronaviruses, presents with S glycoproteins on the membrane that plays an integral role in the virus binding with the angiotensin-converting enzyme 2 (ACE2) receptor. The ACE2 receptor is an intramembrane receptor on the type II pneumocytes, where the virus is able to replicate after getting endocytosed within the cytoplasm. As the viral load increases within the alveolar cell, the alveolar epithelial cell will burst, releasing the newly replicated viral RNA. Elderly individuals are at a greater risk of infection due to weakened immune systems and pre-existing medical conditions resulting in a compromised immune response, also increasing the susceptibility of infection. Infected individuals presenting with mild to moderate symptoms are recommended to self-isolate as the majority will recover without any intervention.


title: Infection prevention and control (IPC) for novel coronavirus (COVID-19)

text: Graphical Abstract.


title: Chronic obstructive pulmonary disease in China: a nationwide prevalence study

text: BACKGROUND: Because of the rapid change in economic development and lifestyle in China, and the ageing population, concerns have grown that chronic obstructive pulmonary disease (COPD) could become epidemic. An up-to-date nationwide estimation of COPD prevalence in China is needed. METHODS: We did a cross-sectional survey of a nationally representative sample of individuals from mainland China aged 40 years or older. The primary outcome was COPD, defined according to the 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) lung function criteria. FINDINGS: Between Dec 29, 2014, and Dec 31, 2015, 66 752 adults were recruited to the study population. The estimated standardised prevalence of COPD was 13·6% (95% CI 12·0–15·2). The prevalence of COPD differed significantly between men and women (19·0%, 95% CI 16·9–21·2 vs 8·1%, 6·8–9·3; p<0·0001), mainly because of a significant difference in smoking status between men and women (current smokers 58·2% vs 4·0%). The prevalence of COPD differed by geographic region, with the highest prevalence in southwest China (20·2%, 95% CI 14·7–25·8) and the lowest in central China (10·2%, 8·2–12·2). Among adults with COPD, 56·4% (95% CI 53·7–59·2) had mild disease (GOLD stage I), 36·3% (34·3–38·3) had moderate disease (GOLD stage II), 6·5% (5·5–7·4) had severe disease (GOLD stage III), and 0·9% (0·6–1·1) had very severe disease (GOLD stage IV). INTERPRETATION: In a large, nationally representative sample of adults aged 40 years or older, the estimated overall prevalence of COPD in China in 2014–15 was 13·6%, indicating that this disease has become a major public-health problem. Strategies aimed at prevention and treatment of COPD are needed urgently. FUNDING: Chinese Central Government, the Ministry of Science and Technology of The People's Republic of China, and the National Natural Science Foundation of China.


title: Additional molecular testing of saliva specimens improves the detection of respiratory viruses

text: Emerging infectious diseases in humans are often caused by respiratory viruses such as pandemic or avian influenza viruses and novel coronaviruses. Microbiological testing for respiratory viruses is important for patient management, infection control and epidemiological studies. Nasopharyngeal specimens are frequently tested, but their sensitivity is suboptimal. This study evaluated the incremental benefit of testing respiratory viruses in expectorated saliva using molecular assays. A total of 258 hospitalized adult patients with suspected respiratory infections were included. Their expectorated saliva was collected without the use of any special devices. In the first cohort of 159 patients whose nasopharyngeal aspirates (NPAs) tested positive for respiratory viruses during routine testing, the viral load was measured using quantitative reverse transcription PCR. Seventeen percent of the patients (27/159) had higher viral loads in the saliva than in the NPA. The second cohort consisted of 99 patients whose NPAs tested negative for respiratory viruses using a direct immunofluorescence assay. Their NPA and saliva specimens were additionally tested using multiplex PCR. In these patients, the concordance rate by multiplex PCR between NPA and saliva was 83.8%. Multiplex PCR detected viruses in saliva samples from 16 patients, of which nine (56.3%) had at least one virus that was not detected in the NPA. Decisions on antiviral or isolation precautions would be affected by salivary testing in six patients. Although NPAs have high viral loads and remain the specimen of choice for most patients with respiratory virus infections, supplementary molecular testing of saliva can improve the clinical management of these patients.


title: In the Same Storm but Different Boats

text: People’s experiences of the COVID-19 pandemic vary widely, with some groups suffering disproportionately.


title: Longitudinal and cross-sectional detection of four bovine enteric viruses by multiplex- reverse transcription polymerase chain reaction: Identification of possible indicator viruses to assess biosecurity level at bovine farms

text: It can be judged that if the detection frequency of prevalent pathogenic viruses decreases, biosecurity has been enhanced. To monitor bovine farm biosecurity levels, one-step multiplex reverse transcription polymerase chain reaction (RT-PCR) for the simultaneous detection of group A rotavirus (RVA), bovine torovirus (BToV), bovine enterovirus (BEV), and bovine coronavirus (BCV) was designed, with the aim of configuring candidates for “viral pathogen indicators”. A total of 322 bovine fecal samples were collected from calves aged less than three months at 48 bovine farms in Ibaraki and Chiba prefectures. At farm A, 20 calves were selected and sampled weekly for 12 weeks (184 samples); at farm B, 10 calves were selected and sampled for five weeks (50 samples); and at the rest of the 46 farms, 88 calves were sampled once. The screening on the 358 field samples proved positive for 27 RVA, 4 BToV, 55 BEV, and 52 BCV. In the successive sampling, RVA was detected once but not continuously, whereas BEV and BCV were detected in succession for up to five weeks. The results revealed that RVA was the primary agent among the positive samples obtained from calves aged three weeks or less, while BEV was the primary among those from the older than three weeks old. They can be employed as useful viral pathogen indicators for soundly evaluating biosecurity at bovine farms.


title: Commentary on “Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open label non-randomized clinical trial” by Gautret et al

text: The results of a clinical trial comparing hydroxychloroquine with or without azithromycin to the standard of care for the treatment of COVID-19 were recently published by Philippe Gautret et al. This study provides outstanding results for the combination of hydroxychloroquine and azithromycin over the standard of care, but the evidence was deemed insufficiently robust to warrant a public health decision to widen the use of hydroxychloroquine for the treatment of COVID-19. We provide a scientific critical review of the Gautret et al. publication, put the results in the context of the current knowledge, provide an evaluation of the validity of the results (from a methodologic perspective), and discuss public health implications. The study has a number of limitations, including small sample size, lack of comparability between patients in active treatment and control arms, lack of blinding, use of interim analyses without controlling for the risk of type 1 error, use of analysis in the per-protocol population instead of the intention-to-treat population, and inconsistencies between the study protocol and article. However, none of these observations is of a nature to reverse the conclusions. The study brings useful knowledge consistent with available evidence and clinical practice from China and South Korea, which could have prompted quicker policy decision-making.


Letter: does the IFNL4 gene discovery really provide a causal role for the IL28B haplotype blocks? Authors' reply


title: Viral vectors for production of recombinant proteins in plants

text: Global demand for recombinant proteins has steadily accelerated for the last 20 years. These recombinant proteins have a wide range of important applications, including vaccines and therapeutics for human and animal health, industrial enzymes, new materials and components of novel nano‐particles for various applications. The majority of recombinant proteins are produced by traditional biological “factories,” that is, predominantly mammalian and microbial cell cultures along with yeast and insect cells. However, these traditional technologies cannot satisfy the increasing market demand due to prohibitive capital investment requirements. During the last two decades, plants have been under intensive investigation to provide an alternative system for cost‐effective, highly scalable, and safe production of recombinant proteins. Although the genetic engineering of plant viral vectors for heterologous gene expression can be dated back to the early 1980s, recent understanding of plant virology and technical progress in molecular biology have allowed for significant improvements and fine tuning of these vectors. These breakthroughs enable the flourishing of a variety of new viral‐based expression systems and their wide application by academic and industry groups. In this review, we describe the principal plant viral‐based production strategies and the latest plant viral expression systems, with a particular focus on the variety of proteins produced and their applications. We will summarize the recent progress in the downstream processing of plant materials for efficient extraction and purification of recombinant proteins. J. Cell. Physiol. 216: 366–377, 2008. © 2008 Wiley‐Liss, Inc.


title: A sorghum xylanase inhibitor-like protein with highly potent antifungal, antitumor and HIV-1 reverse transcriptase inhibitory activities

text: Abstract A 25-kDa protein, with an N-terminal amino acid sequence homologous to that of xylanase inhibitor and designated as xylanase inbibitor-like protein (XILP) was purified from sorghum seeds. The isolation protocol consisted of affinity chromatography, ion exchange chromatography, and gel filtration. XILP inhibited mycelial growth in various phytopathogenic fungi. The antifungal activity was thermostable and pH-stable. XILP inhibited proliferation of various cancer cell lines but did not do so in human embryonic liver (WRL 68) cells. There was no mitogenic activity toward mouse splenocytes. XILP reduced the activity of HIV-1 reverse transcriptase with an IC50 of 11.1μM, but lacked inhibitory activity toward HIV-1 integrase and SARS coronavirus proteinase. In conclusion, sorghum XILP is thermostable and pH stable and exhibits potent antifungal, antiproliferative, and HIV-1 reverse transcriptase inhibitory activities.


Dramatic reduction of psychiatric emergency consultations during lockdown linked to COVID‐19 in Paris and suburbs


What Should the Dean Do?


title: Comparison of Cepheid® Xpert Flu and Roche RealTime Ready Influenza A/H1N1 Detection Set for detection of influenza A/H1N1

text: Abstract Objective To compare two influenza polymerase chain reaction (PCR) methods. Methods A total of 749 suspected MERS-CoV patients presenting at Johns Hopkins Aramco Healthcare, Saudi Arabia, each submitted a clinical sample for influenza A reflex testing using the on-site Cepheid® Xpert Flu assay and at the Ministry of Health laboratory by the Roche PCR assay. Results There was 92.12% overall agreement between the two methods. Specificity of the Cepheid® Xpert Flu was 95.8% for H1N1 and 94.4% for total influenza A. Cepheid® Xpert Flu sensitivity for influenza A was 100% for younger patients (0–19-year age group) but significantly lower both for older patients (68.2% for 60–79-year and 50% for ≥80-year age groups) and overall for males compared to females (72.6% and 94.0%, respectively). Conclusions Specificity of the Cepheid® Xpert Flu test was high; however, sensitivity for total influenza A was lower particularly in males and older patients.


title: COVID‐19 and the treatment of acute appendicitis in Ireland: a new era or short‐term pivot?

text: Covid-19 (SARS-CoV-2) has caused major disruption to healthcare practices globally. The reality of a pandemic rapidly overwhelming healthcare systems has been alarming and countries earlier in their curves have sought to implement the lessons from others' experiences. Surgery is among the many services impacted by re-structuring to provide surge capacity in Ireland. Since the commencement of our national mitigation phase in March 2020, with subsequent escalation to lock-down on March 17th , elective care has been reduced to only those most time-sensitive (e.g. oncological care).


title: Antiviral Peptides: Identification and Validation

text: Despite rapid advances in the human healthcare, the infection caused by certain viruses results in high morbidity and mortality accentuate the importance for development of new antivirals. The existing antiviral drugs are limited, due to their inadequate response, increased rate of resistance and several adverse side effects. Therefore, one of the newly emerging field “peptide-based therapeutics” against viruses is being explored and seems promising. Over the last few years, a lot of scientific effort has been made for the identification of novel and potential peptide-based therapeutics using various advanced technologies. Consequently, there are more than 60 approved peptide drugs available for sale in the market of United States, Europe, Japan, and some Asian countries. Moreover, the number of peptide drugs undergoing the clinical trials is rising gradually year by year. The peptide-based antiviral therapeutics have been approved for the Human immunodeficiency virus (HIV), Influenza virus and Hepatitis virus (B and C). This review enlightens the various peptide sources and the different approaches that have contributed to the search of potential antiviral peptides. These include computational approaches, natural and biological sources (library based high throughput screening) for the identification of lead peptide molecules against their target. Further the applications of few advanced techniques based on combinatorial chemistry and molecular biology have been illustrated to measure the binding parameters such as affinity and kinetics of the screened interacting partners. The employment of these advanced techniques can contribute to investigate antiviral peptide therapeutics for emerging infections.


title: Tough challenges for testing Ebola therapeutics

text: Therapies for Ebola virus disease are urgently needed, but they must be rigorously tested for safety and efficacy before any mass roll-out to patients. Fiona Fleck reports.


title: Ribosome structure: revisiting the connection between translational accuracy and unconventional decoding

text: Abstract The ribosome is a molecular machine that converts genetic information in the form of RNA, into protein. Recent structural studies reveal a complex set of interactions between the ribosome and its ligands, mRNA and tRNA, that indicate ways in which the ribosome could avoid costly translational errors. Ribosomes must decode each successive codon accurately, and structural data provide a clear indication of how ribosomes limit recruitment of the wrong tRNA (sense errors). In a triplet-based genetic code there are three potential forward reading frames, only one of which encodes the correct protein. Errors in which the ribosome reads a codon out of the normal reading frame (frameshift errors) occur less frequently than sense errors, although it is not clear from structural data how these errors are avoided. Some mRNA sequences, termed programmed-frameshift sites, cause the ribosome to change reading frame. Based on recent work on these sites, this article proposes that the ribosome uses the structure of the codon–anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.


title: Lessening of porcine epidemic diarrhoea virus susceptibility in piglets after editing of the CMP-N-glycolylneuraminic acid hydroxylase gene with CRISPR/Cas9 to nullify N-glycolylneuraminic acid expression

text: Porcine epidemic diarrhoea virus (PEDV) devastates the health of piglets but may not infect piglets whose CMP-N-glycolylneuraminic acid hydroxylase (CMAH) gene mutated (knockouts, KO) by using CRISPR/Cas9 gene editing techniques. This hypothesis was tested by using KO piglets challenged with PEDV. Two single-guide RNAs targeting the CMAH gene and Cas9 mRNA were microinjected into the cytoplasm of newly fertilized eggs; 4 live founders generated and proven to be biallelic KO, lacking detectable N-glycolylneuraminic acid (NGNA). The founders were bred, and homozygous offspring were obtained. Two-day-old (in exps. I and III) and 3-day-old (in exp. II) KO and wild-type (WT) piglets were inoculated with TCID50 1x103 PEDV and then fed 20 mL of infant formula (in exps. I and II) or sow’s colostrum (in exp. III) every 4 hours. In exp. III, the colostrum was offered 6 times and was then replaced with Ringer/5% glucose solution. At 72 hours post-PEDV inoculation (hpi), the animals were euthanized for necropsy, and their intestines were sampled. In all 3 experiments, the piglets showed apparent outward clinical manifestations suggesting that infection occurred despite the CMAH KO. In exp. I, all 6 WT piglets and only 1 of 6 KO piglets died at 72 hpi. Histopathology and immunofluorescence staining showed that the villus epithelial cells of WT piglets were severely exfoliated, but only moderate exfoliation and enterocyte vacuolization was observed in KO piglets. In exp. II, delayed clinical symptoms appeared, yet the immunofluorescence staining/histopathologic inspection (I/H) scores of the two groups differed little. In exp. III, the animals exhibited clinical and pathological signs after inoculation similar to those in exp. II. These results suggest that porcine CMAH KO with nullified NGNA expression are not immune to PEDV but that this KO may lessen the severity of the infection and delay its occurrence.


title: Evaluation of Anyplex™ II RV16 and RB5 real-time RT-PCR compared to Seeplex® RV15 OneStep ACE and PneumoBacter ACE for the simultaneous detection of upper respiratory pathogens

text: Abstract This prospective study was performed to evaluate and compare the performance of the multiplex PCR Seeplex ® assays and Anyplex™ II assays. From May 2014 until April 2016, a total of 247 respiratory samples were collected in Okinawa, Japan. Multiple respiratory pathogens were detected in 37% of patients with positive results. The most prevalent pathogens were influenza A virus and respiratory syncytial virus B. Despite minor differences in capabilities, both the Seeplex ® assays and Anyplex™ II assays can be easily implemented in diagnostic or research laboratories to optimize the detection and management of respiratory pathogen induced diseases.


title: Hong Kong Registry Report 2004

text: This report is based on data (up to 31 March 2004) from the Renal Registry of the Hospital Authority of Hong Kong, and accounts for 90-95% of all patients receiving renal replacement therapy (RRT) in the territory. Patients receiving RRT in the private sector are not included in this report. The number of patients receiving RRT was 6,054 (889 per million population [pmp]), of whom 51.6% (3,123, 451 pmp) were receiving peritoneal dialysis (PD), 10.9% (662, 97 pmp) hemodialysis (HD), and 37.5% (2,269, 334 pmp) had functioning kidney transplants. The net increase from the previous year in the number of patients receiving RRT was 3.1%. The incidence of end-stage renal failure in patients undergoing RRT was 954 (140 pmp). The median ages of existing and new patients receiving RRT were 55 and 56 years, respectively. There was a trend towards an increasing number of elderly dialysis patients. Diabetes was the third major cause of renal failure among existing RRT patients and the most common cause of renal failure in new cases. The rate of serologic positivity for hepatitis B infection in RRT patients was 9.68%, while that for hepatitis C infection was 3.28%. In Hong Kong, most patients were put on PD when RRT was required. Of all patients on dialysis, 83% were on PD, of whom 94.8% were on continuous ambulatory peritoneal dialysis (CAPD). Most CAPD patients were on disconnect systems. HD was used in 17.5% of all patients on dialysis. Of the 2,269 patients with functioning kidney transplants, 836 (36.8%) were transplanted in Hong Kong. Of these, 495 (59.2%) had undergone cadaveric kidney transplantation. Of all patients receiving RRT, 30% were receiving erythropoietin. For the year ending 31 March 2004, the annual crude mortality rate for all RRT was 10% (15.3% for PD, 13% for HD, and 1.9% for transplantation). The major causes of death were infection, cardiovascular disease, and cerebrovascular accident. The 1- and 5-year survival rates for patients with kidney transplantation performed in Hong Kong between 1 April 1997 and 31 March 2003 were 98.6% and 96.5%, respectively, for living related kidney transplants, and 96.1% and 91.2%, respectively, for cadaveric kidney transplants. The 1- and 5- year graft survival rates were 91.1% and 86.1% (death censored) and 90.5% and 85.6% (death not censored) for living related kidney transplants, and 89% and 83% (death censored) and 86% and 79% (death not censored) for cadaveric kidney transplants. The overall peritonitis rate for all chronic PD systems for the year ending 31 March 2004 was one episode per 27.7 months.


Romeo and Juliet: revisited (at the time of COVID-19)


The Value of Headache‐Specific Recommendations During COVID‐19


title: Klebsiella pneumoniae pharyngitis mimicking malignancy: a diagnostic dilemma

text: Acute pharyngitis is a common disease. However, acute pharyngitis caused by Klebsiella pneumoniae with a gross appearance mimicking hypopharyngeal malignancy has never previously been reported. We report the case of a 57-year-old man with a right hypopharyngeal tumor which was disclosed by fiberoptic laryngoscopy and computed tomography scan. However, both the frozen and final pathologies showed no evidence of malignant cells, and a bacterial culture revealed the growth of K. pneumoniae. The hypopharyngeal lesion completely regressed after 2 weeks of antibiotic treatment. Clinicians should perform biopsy along with tissue culture for tumor-like lesions because infectious agents can lead to lesions with malignancy-like appearance.


title: A Single V672F Substitution in the Spike Protein of Field-Isolated PEDV Promotes Cell–Cell Fusion and Replication in VeroE6 Cells

text: While porcine epidemic diarrhea virus (PEDV) infects and replicates in enterocytes lining villi of neonatal piglets with high efficiency, naturally isolated variants typically grow poorly in established cell lines, unless adapted by multiple passages. Cells infected with most cell-adapted PEDVs usually displayed large syncytia, a process triggered by the spike protein (S). To identify amino acids responsible for S-mediated syncytium formation, we constructed and characterized chimeric S proteins of the cell-adapted variant, YN144, in which the receptor binding domain (RBD) and S1/S2 cleavage site were replaced with those of a poorly culturable field isolate (G2). We demonstrated that the RBD, not the S1/S2 cleavage site, is critical for syncytium formation mediated by chimeric S proteins. Further mutational analyses revealed that a single mutation at the amino acid residue position 672 (V672F) could enable the chimeric S with the entire RBD derived from the G2 strain to trigger large syncytia. Moreover, recombinant PEDV viruses bearing S of the G2 strain with the single V672F substitution could induce extensive syncytium formation and replicate efficiently in VeroE6 cells stably expressing porcine aminopeptidase N (VeroE6-APN). Interestingly, we also demonstrated that while the V672F mutation is critical for the syncytium formation in VeroE6-APN cells, it exerts a minimal effect in Huh-7 cells, thereby suggesting the difference in receptor preference of PEDV among host cells.


title: Clinical, laboratory, and radiological features indicative of novel coronavirus disease (COVID‐19) in emergency departments – a multicentre case‐control study in Hong Kong

text: OBJECTIVES: Little is known about the value of routine clinical assessment in identifying patients with coronavirus disease 2019 (COVID‐19) in the emergency department (ED). We aimed to compare the exposure history, signs and symptoms, laboratory, and radiographic features of ED patients who tested positive and negative for COVID‐19. METHODS: This was a case‐control study in seven EDs in Hong Kong from 20 January to 29 February 2020. Thirty‐seven patients with laboratory‐confirmed COVID‐19 were age‐ and gender‐matched to 111 controls. We compared the groups with univariate analysis and calculated the odds ratio (OR) of having COVID‐19 for each characteristic that was significantly different between the groups with adjustment for age and presumed location of acquiring the infection. RESULTS: There were no significant differences in patient characteristics and reported symptoms between the groups. A positive contact history within 14 days (adjusted OR 37.61, 95% CI 10.86‐130.19), bilateral chest radiograph shadow (adjusted OR 13.19, 95% CI 4.66‐37.35), having prior medical consultation (adjusted OR 7.43, 95% 2.89 ‐19.09), a lower white blood cell count (adjusted OR 1.30, 95% CI 1.11‐1.51), and a lower platelet count (adjusted OR 1.07, 95% CI 1.01‐1.12) were associated with a higher odds of COVID‐19 separately. A higher neutrophil count was associated with a lower odds of COVID‐19 (adjusted OR 0.77, 95% CI 0.65‐0.91). CONCLUSION: This study highlights a number of clinical features that may be useful in identifying high‐risk patients for early testing and isolation while waiting for the test result. Further studies are warranted to verify the findings. This article is protected by copyright. All rights reserved


title: Structure of the S1 subunit C-terminal domain from bat-derived coronavirus HKU5 spike protein

text: Abstract Accumulating evidence indicates that MERS-CoV originated from bat coronaviruses (BatCoVs). Previously, we demonstrated that both MERS-CoV and BatCoV HKU4 use CD26 as a receptor, but how the BatCoVs evolved to bind CD26 is an intriguing question. Here, we solved the crystal structure of the S1 subunit C-terminal domain of HKU5 (HKU5-CTD), another BatCoV that is phylogenetically related to MERS-CoV but cannot bind to CD26. We observed that the conserved core subdomain and those of other betacoronaviruses (betaCoVs) have a similar topology of the external subdomain, indicating the same ancestor of lineage C betaCoVs. However, two deletions in two respective loops located in HKU5-CTD result in conformational variations in CD26-binding interface and are responsible for the non-binding of HKU5-CTD to CD26. Combined with sequence variation in the HKU5-CTD receptor binding interface, we propose the necessity for surveilling the mutation in BatCoV HKU5 spike protein in case of bat-to-human interspecies transmission.


title: The comparative pathology of severe acute respiratory syndrome and avian influenza A subtype H5N1—a review

text: Summary The pathology of 2 zoonotic human viral infections that recently emerged, severe acute respiratory syndrome (SARS) due to coronavirus (SARS-CoV) and avian influenza A subtype H5N1, is reviewed and compared based on the literature and the cases examined by the authors. Pneumocytes are the primary target of infection resulting in diffuse alveolar damage. Systemic cytokine activation results in hemophagocytic syndrome, lymphoid depletion, and skeletal muscle fiber necrosis. Severe acute respiratory syndrome induces a more fibrocellular intra-alveolar organization with a “bronchiolitis obliterans organizing pneumonia”–like pattern and presence of multinucleated histiocytes and pneumocytes. H5N1 causes a more fulminant and necrotizing diffuse alveolar damage with patchy and interstitial paucicellular fibrosis. Severe acute respiratory syndrome associated coronavirus persists in the lung up to the second month, whereas H5N1 persists in the lung up to the third week. Severe acute respiratory syndrome associated coronavirus disseminates to blood, urine, feces, gastrointestinal tract, and liver. There is recent report of possible cerebral involvement by H5N1 and its isolation in the blood, gastrointestinal tract, and cerebrospinal fluid. More pathologic studies are urgently needed.


title: Great Green Transition and Finance

text: European governments are struggling to regain economic strength in the coronavirus pandemic as in many countries the number of new infections seems to gradually subside. Growth rates deep in the red call for a reconstruction programme when the crisis is finally manageable and economic activity can resume. Amidst this, there are again influential groups that claim “this is not the time to insist on strict climate protection goals”. On the contrary, the ongoing COVID-19 crisis has clearly illustrated what climate disasters, often occurring locally, could do to the life of citizens. The reconstruction programme needs to initiate the great green transition. The transformation from a climate-distorting to a climate-protecting economy opens up investment opportunities and points to financing needs comparable with those necessary for the rebuilding of the European economy after World War II. The great green transition is a unique chance to pursue policies for a new and sustainable growth regime.


title: Chapter 15 Viral Diseases of Common Marmosets

text: Abstract Common marmosets are highly susceptible to several viral pathogens that exist as latent or subclinical infections in their natural reservoir hosts but cause severe disease or death when interspecies transmission occurs. Examples of such viruses in marmosets are herpes simplex virus infections, parainfluenza virus 1 infections, and measles acquired from humans, Saimiriine herpesvirus 1 infection after transmission from squirrel monkeys, and infections with lymphocytic choriomeningitis virus originating from mice. Other relevant viral infections causing spontaneous disease in common marmoset colonies include cowpox virus infections and paramyxovirus saguinus infections. Callitrichine herpesvirus 3 is a newly recognized lymphocryptovirus that is associated with the development of intestinal lymphoproliferative disease in common marmosets. Most viral pathogens causing disease in common marmosets are potential zoonotic agents, and protective measures should be implemented when handling these small New World monkeys.


title: Pandemic Influenza Planning, United States, 1978–2008

text: During the past century, 4 influenza pandemics occurred. After the emergence of a novel influenza virus of swine origin in 1976, national, state, and local US public health authorities began planning efforts to respond to future pandemics. Several events have since stimulated progress in public health emergency planning: the 1997 avian influenza A(H5N1) outbreak in Hong Kong, China; the 2001 anthrax attacks in the United States; the 2003 outbreak of severe acute respiratory syndrome; and the 2003 reemergence of influenza A(H5N1) virus infection in humans. We outline the evolution of US pandemic planning since the late 1970s, summarize planning accomplishments, and explain their ongoing importance. The public health community’s response to the 2009 influenza A(H1N1)pdm09 pandemic demonstrated the value of planning and provided insights into improving future plans and response efforts. Preparedness planning will enhance the collective, multilevel response to future public health crises.


title: Role of emerging respiratory viruses in children with severe acute wheezing

text: BACKGROUND: Acute wheezing episodes are frequently associated with respiratory viral infections in children. However, the role of the recently described respiratory viruses is not yet fully understood. OBJECTIVE: The main objective of this study was to estimate the frequency of human metapneumovirus (HMPV), human bocavirus (HBoV), and 14 other respiratory viruses in hospitalized children with acute wheezing. METHODS: A prospective study was conducted on children <14 years old, admitted with an acute expiratory wheezing episode from September 2005 to June 2008. Viruses were detected in nasopharyngeal aspirates by polymerase chain reaction. Clinical data were prospectively recorded. RESULTS: A viral pathogen was identified in 444 (71%) out of 626 hospitalized acute wheezing episodes. Respiratory syncytial virus (RSV) was the most frequently detected (27%), followed by rhinovirus (24%), adenovirus (17.8%), HBoV (16%), and HMPV (4.7%). The rate of viral detection was significantly higher in infants (77.3%), than in older children (59.8%) (P < 0.001). RSV and HBoV were more prevalent in infants (P < 0.001) than in older children. CONCLUSION: The most prevalent viruses found in severe acute wheezing episodes were RSV and rhinovirus not only in childhood, but also in infancy. However, other emerging viruses such as HBoV and metapneumovirus also play an important role in wheezing episodes. Pediatr Pulmonol. 2010; 45:585–591. © 2010 Wiley‐Liss, Inc.


title: Faecal viruses of dogs — an electron microscope study

text: Abstract Faecal samples from 112 dogs both with and without diarrhoea were screened for parvovirus by a haemagglutination titration test and then examined by electron microscopy for the presence of viruses and virus-like particles. On the basis of morphology eight distinct viruses or virus-like particles were identified. Particles identified were coronaviruses, coronavirus-like particles, rotavirus-like particles, papovavirus-like particles, torovirus-like particles, picornavirus-like particles, 27 nm virus-like particles with projections and parvovirus-like particles which did not cause haemagglutination.


title: Emerging Respiratory Viruses in Children

text: Respiratory viral infections are a leading cause of pediatric disease. Emerging respiratory viruses can cause outbreaks with significant morbidity and mortality or circulate routinely. The rapid identification of pathogens, epidemiologic tracing, description of symptoms, and development of preventative and therapeutic measures are crucial to limiting the spread of these viruses. Some emerging viruses, such as rhinovirus C and influenza C, circulate yearly but were previously undetected due to limited diagnostic methods. Although some pathogens have a geographic focus, globalization dictates that providers be aware of all emerging diseases in order to recognize outbreaks and diagnose and treat patients.


title: Localization of proteins to the Golgi apparatus

text: For the Golgi apparatus to perform its various unique roles it must maintain a population of resident proteins. These residents include the enzymes that modify the proteins and lipids passing through the Golgi, as well as the proteins involved in vesicle formation and protein sorting. For several of these residents, it has been possible to identify regions that are crucial for specifying a Golgi localization. Consideration of how these targeting domains could function has provided insights into the organization of the Golgi and its protein and lipid content.


title: Is diet partly responsible for differences in COVID-19 death rates between and within countries?

text: Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.


Subject and Author Indexes for volume 62


Respiratory Viral Infections in Developing Countries: Common, Severe, and Unrecognized


title: Antigenicity and receptor-binding ability of recombinant SARS coronavirus spike protein

text: Abstract Severe acute respiratory syndrome (SARS) is an emerging infectious disease associated with a novel coronavirus and causing worldwide outbreaks. SARS coronavirus (SARS-CoV) is an enveloped RNA virus, which contains several structural proteins. Among these proteins, spike (S) protein is responsible for binding to specific cellular receptors and is a major antigenic determinant, which induces neutralizing antibody. In order to analyze the antigenicity and receptor-binding ability of SARS-CoV S protein, we expressed the S protein in Escherichia coli using a pET expression vector. After the isopropyl-β-d-thiogalactoside induction, S protein was expressed in the soluble form and purified by nickel-affinity chromatography to homogeneity. The amount of S protein recovered was 0.2–0.3mg/100ml bacterial culture. The S protein was recognized by sera from SARS patients by ELISA and Western blot, which indicated that recombinant S protein retained its antigenicity. By biotinylated ELISA and Western blot using biotin-labeled S protein as the probe, we identified 130-kDa and 140-kDa proteins in Vero cells that might be the cellular receptors responsible for SARS-CoV infection. Taken together, these results suggested that recombinant S protein exhibited the antigenicity and receptor-binding ability, and it could be a good candidate for further developing SARS vaccine and anti-SARS therapy.


title: Biostudy on Traditional Chinese Medicine Massa Medicata Fermentata

text: [Image: see text] Massa Medicata Fermentata (MMF) has been used for a long time by the Chinese. MMF is used widely in feed additives and human medicinal applications throughout the world; however, there have only been a few reports about the biostudy of its fermentation mechanism and medicinal ingredients. To safely use MMF, we observed the changes in the ingredients and amylase activity for several raw materials during the fermentation process of MMF. We are going to explore the basis of pharmacodynamic substances and the purpose of MMF to provide support for safe use in clinics. This biostudy data demonstrated that the ingredients such as amygdalin, benzaldehyde, and rutin were gradually degraded during the process of fermentation, and the fermented MMF did not contain amygdalin and benzaldehyde. The HPLC fingerprint of fermented MMF for 7 days is similar to the chemical composition of the original unfermented MMF with a similarity of only 0.106. Meanwhile, the activities of amylase in fermented MMF had gradually increased, and the content of organic acids also had increased. According to our biostudy, we found that the raw material chemical composition of MMF in the process of fermentation was affected by microorganisms and various substances. The conclusions of our study determined that the initial components of MMF are not identical to the pharmacodynamic components. We also conclude that amylase activity explains the pharmacological activity of MMF to a certain extent, but it is likely not the only factor. The implication not only provides the initial knowledge of MMF but also implies the further exploration of this popular traditional medicine.


title: Estimating influenza vaccine effectiveness using routine surveillance data among children aged 6–59 months for five consecutive influenza seasons

text: Summary Objectives We aimed to estimate the pooled vaccine effectiveness (VE) in children over five winters through data linkage of two existing surveillance systems. Methods Five test-negative case–control studies were conducted from November to February during the 2004/2005 to 2008/2009 seasons. Sentinel physicians from the Viral Surveillance Network enrolled children aged 6–59 months with influenza-like illness to collect throat swabs. Through linking with a nationwide vaccination registry, we measured the VE with a logistic regression model adjusting for age, gender, and week of symptom onset. Both fixed-effects and random-effects models were used in the meta-analysis. Results Four thousand four hundred and ninety-four subjects were included. The proportion of influenza test-positive subjects across the five seasons was 11.5% (132/1151), 7.2% (41/572), 23.9% (189/791), 6.6% (75/1135), and 11.2% (95/845), respectively. The pooled VE was 62% (95% confidence interval (CI) 48–83%) in both meta-analysis models. By age category, VE was 51% (95% CI 23–68%) for those aged 6–23 months and 75% (95% CI 60–84%) for those aged 24–59 months. Conclusions Influenza vaccination provided measurable protection against laboratory-confirmed influenza among children aged 6–59 months despite variations in the vaccine match during the 2004/2005 to 2008/2009 influenza seasons in Taiwan.


title: Community Respiratory Viruses in Individuals with Human Immunodeficiency Virus Infection

text: Abstract Respiratory viruses, particularly influenza viruses, respiratory syncytial virus (RSV), parainfluenza viruses, and adenoviruses, are ubiquitous pathogens among humans, especially among young children. However, relatively little is known about the impact of these common infections on individuals with the human immunodeficiency virus (HIV). A review of the literature identifies three key areas that need further exploration. First, moderate-to-severe and even fatal lower respiratory viral illnesses in HIV-infected individuals have been reported. In general, the clinical presentation of these respiratory viral infections in persons with HIV infection is similar to their presentation in individuals without HIV infection. The major exception is the occurrence of fulminant, and often fatal, disseminated adenovirus infection in adults and children with HIV disease. Despite these reports, no information is available regarding the frequency of moderate-to-severe respiratory viral illnesses in individuals with HIV infection. Epidemiologic studies of respiratory viral illnesses in cohorts of HIV-infected adults and children are needed. Second, prolonged shedding of respiratory viruses for weeks and even months has been documented in HIV-infected adults and children. The frequency of prolonged shedding in this population has not been well defined, but data from a small newborn cohort study suggest that, at least for RSV, prolonged shedding is common. Prolonged respiratory viral shedding has implications for infection control in medical facilities where HIV-infected individuals are treated and in nursing homes, child care centers, and group foster homes that provide care for HIV-infected individuals. Therapies to help eliminate these chronic viral infections should be explored. Finally, indirect evidence suggests that respiratory viral infection may result in changes in HIV replication and, theoretically, HIV disease progression. Increased HIV-1 replication has been demonstrated in vitro in T lymphoma cells exposed to genetic material from adenovirus. Increased HIV replication in peripheral blood from adults following inactivated influenza vaccination has been reported. The impact of natural respiratory viral infection (and perhaps vaccination against these pathogens) on HIV replication and disease progression will be an important area of study.


title: Molecular epidemiology of influenza, RSV, and other respiratory infections among children in Qatar: A six years report (2012–2017)

text: Abstract Background Studies on the etiology of respiratory infections among children in Qatar and surrounding countries are limited. Objectives To describe the prevalence and seasonality of RSV, influenza, and other respiratory pathogens among children in Qatar. Methods We retrospectively collected and analyzed data of 33,404 children (<15 years) presented with influenza-like illness from 2012 to 2017. Results At least one respiratory pathogen was detected in 26,138 (78%) of patients. Together, human rhinoviruses (HRV), respiratory syncytial virus (RSV), and influenza viruses comprised nearly two-thirds of all cases, affecting 24%, 19.7%, and 18.5%, respectively. A prevalence of 5-10% was recorded for adenovirus, parainfluenza viruses (PIVs), human bocavirus (HboV), and human coronaviruses (HCoVs). Human metapneumovirus (HMPV), enteroviruses, M. pneumonia, and parechovirus had prevalences below 5%. While RSV, influenza, and HMPV exhibited strong seasonal activity in the winter, HRV was active during low RSV and influenza circulation. The burden of RSV exceeds that of influenza among young age groups, whereas influenza correlated positively with age. Further, HRV, adenovirus, influenza, and RSV infection rates varied significantly between male and females. Conclusion This comprehensive multi-year study provides insights into the etiology of ILI among children in Qatar, which represents the Gulf region. Our results reinforce the significance of active surveillance of respiratory pathogens to improve infection prevention and control strategies, particularly among children.


title: Clozapine is strongly associated with the risk of pneumonia and inflammation

text: Clinicians need to remember that (1) systemic inflammations can increase clozapine level; (2) clozapine, by itself, can cause inflammation, particularly during titration that is too rapid for that patient; (3) clozapine may increase the risk of infection; and (4) more specifically, clozapine may be particularly strongly associated with the risk of pneumonia. Pneumonia appears to be associated with high mortality in clozapine patients around the world. Clinicians who are alert to the risk of pneumonia in clozapine patients may significantly decrease mortality in clozapine patients. There is no data on COVID-19 infections in clozapine patients, but based on what we know about clozapine pharmacology, we can hypothesise that clozapine, possibly by impairing immunological mechanisms, may increase the risk of pneumonia in infected patients. More importantly, once fever and/or pneumonia develops, the clozapine dose should be cut in half to decrease the risk of clozapine intoxication. If there is any doubt that in spite of halving the dose there are still signs of clozapine intoxication, completely stopping clozapine may be indicated. Once the signs of inflammation and fever have disappeared, the clozapine dose can be increased to the prior dosage level.


Fremanezumab for migraine prevention: more effective, less costly


title: POXVIRUS TROPISM

text: Despite the success of the WHO-led smallpox eradication programme a quarter of a century ago, there remains considerable fear that variola virus, or other related pathogenic poxviruses such as monkeypox, could re-emerge and spread disease in the human population. Even today, we are still mostly ignorant about why most poxvirus infections of vertebrate hosts show strict species specificity, or how zoonotic poxvirus infections occur when poxviruses occasionally leap into novel host species. Poxvirus tropism at the cellular level seems to be regulated by intracellular events downstream of virus binding and entry, rather than at the level of specific host receptors as is the case for many other viruses. This review summarizes our current understanding of poxvirus tropism and host range, and discusses the prospects of exploiting host-restricted poxvirus vectors for vaccines, gene therapy or tissue-targeted oncolytic viral therapies for the treatment of human cancers.


Joint China-US Call for Employing a Transdisciplinary Approach to Emerging Infectious Diseases


title: Sequence analysis of the spike protein gene of murine coronavirus variants: Study of genetic sites affecting neuropathogenicity

text: Abstract Mouse hepatitis virus (MHV), a coronavirus, causes encephalitis and demyelination in susceptible rodents. Previous investigations have shown that the MHV spike (S) protein is a critical determinant of viral tropism and pathogenicity in mice and rats. To understand the molecular basis of MHV neuropathogenesis, we studied the spike protein gene sequences of several neutralization-resistant variants of the JHM strain of MHV, which were selected with monoclonal antibodies (MAbs) specific for the S protein. We found that variant 2.2-V-1, which was selected with MAb J.2.2 and primarily caused demyelination, had a single point mutation at nucleotide (NT) 3340, as compared to the parental JHM virus, which predominantly caused encephalitis. This site was in the S2 subunit of the S protein. In contrast, variant 7.2-V-1, which was selected with MAb J.7.2 and primarily caused encephalitis, had two point mutations at NT 1766 and 1950, which were in the S1 subunit. Finally, the double mutant 2.2/7.2-V-2, which was selected with both MAbs J.2.2 and J.7.2, and was attenuated with respect to both virulence and the ability to cause demyelination, had a deletion spanning from NT 1523 to 1624 in the S1 and a point mutation at NT 3340 in the S2. We conclude that at least two regions of the S protein contribute to neuropathogenicity of MHV. We have also isolated a partial revertant of 2.2-V-1, which was partially resistant to MAb 1.2.2 but retained the same neuropathogenicity as the variant 2.2-V-1. This revenant retained the mutation at NT 3340, but had a second-site mutation at NT 1994, further confirming that NT 3340 contributed to the pathogenic phenotype of MHV. By comparing these results with MHV variants isolated in other laboratories, which had mutations in other sites on the S gene and yet retained the demyelinating ability, we suggest that the ability of JHM viruses to induce demyelination is determined by the interaction of multiple sites on the S gene, rather than the characteristics of a single, unique site. Our study also revealed the possible presence of microheterogeneity of S gene sequence, particularly in the S1 region, in these viruses. The sequence microheterogeneity may also contribute to the differences in their biological properties.


title: Effects of service changes affecting distance/time to access urgent and emergency care facilities on patient outcomes: a systematic review

text: BACKGROUND: Reconfiguration of urgent and emergency care services often increases travel time/distance for patients to reach an appropriate facility. Evidence of the effects of reconfiguration is important for local communities and commissioners and providers of health services. METHODS: We performed a systematic review of the evidence regarding effects of service reconfigurations that increase the time/distance for some patients to reach an urgent and emergency care (UEC) facility. We searched seven bibliographic databases from 2000 to February 2019 and used citation tracking and reference lists to identify additional studies. We included studies of any design that compared outcomes for people with conditions requiring emergency treatment before and after service reconfiguration with an associated change in travel time/distance to access UEC. Studies had to be conducted in the UK or other developed countries. Data extraction and quality assessment (using the Joanna Briggs Institute checklist for quasi-experimental studies) were undertaken by a single reviewer with a sample checked for accuracy and consistency. We performed a narrative synthesis of the included studies. Overall strength of evidence was assessed using a previously published method that considers volume, quality and consistency. RESULTS: We included 12 studies, of which six were conducted in the USA, two in the UK and four in other European countries. The studies used a variety of observational designs, with before–after and cohort designs being most common. Only two studies included an independent control site/sites where no reconfiguration had taken place. The reconfigurations evaluated in these studies reported relatively small effects on average travel times/distance. DISCUSSION: For studies of general UEC populations, there was no convincing evidence as to whether reconfiguration affected mortality risk. However, evidence of increased risk was identified from studies of patients with acute myocardial infarction, particularly 1 to 4 years after reconfiguration. Evidence for other conditions was inconsistent or very limited. CONCLUSIONS: We found insufficient evidence to determine whether increased distance to UEC increases mortality risk for the general population of people requiring UEC, although this conclusion may not extend to people with specific conditions.


title: Genomewide Association Study of Severe Covid-19 with Respiratory Failure

text: BACKGROUND: There is considerable variation in disease behavior among patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19). Genomewide association analysis may allow for the identification of potential genetic factors involved in the development of Covid-19. METHODS: We conducted a genomewide association study involving 1980 patients with Covid-19 and severe disease (defined as respiratory failure) at seven hospitals in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe. After quality control and the exclusion of population outliers, 835 patients and 1255 control participants from Italy and 775 patients and 950 control participants from Spain were included in the final analysis. In total, we analyzed 8,582,968 single-nucleotide polymorphisms and conducted a meta-analysis of the two case–control panels. RESULTS: We detected cross-replicating associations with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genomewide level (P<5×10(−8)) in the meta-analysis of the two case–control panels (odds ratio, 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.15×10(−10); and odds ratio, 1.32; 95% CI, 1.20 to 1.47; P=4.95×10(−8), respectively). At locus 3p21.31, the association signal spanned the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at locus 9q34.2 coincided with the ABO blood group locus; in this cohort, a blood-group–specific analysis showed a higher risk in blood group A than in other blood groups (odds ratio, 1.45; 95% CI, 1.20 to 1.75; P=1.48×10(−4)) and a protective effect in blood group O as compared with other blood groups (odds ratio, 0.65; 95% CI, 0.53 to 0.79; P=1.06×10(−5)). CONCLUSIONS: We identified a 3p21.31 gene cluster as a genetic susceptibility locus in patients with Covid-19 with respiratory failure and confirmed a potential involvement of the ABO blood-group system. (Funded by Stein Erik Hagen and others.)


title: Severe neurologic syndrome associated with Middle East respiratory syndrome corona virus (MERS-CoV)

text: BACKGROUND: Since the identification of the first case of infection with the Middle East respiratory syndrome corona virus (MERS-CoV) in Saudi Arabia in June 2012, the number of laboratory-confirmed cases has exceeded 941 cases globally, of which 347 died. The disease presents as severe respiratory infection often with shock, acute kidney injury, and coagulopathy. Recently, we observed three cases who presented with neurologic symptoms. These are so far the first reported cases of neurologic injury associated with MERS-CoV infection. METHODS: Data was retrospectively collected from three patients admitted with MERS-CoV infection to Intensive Care unit (ICU) at King Abdulaziz Medical City, Riyadh. They were managed separately in three different wards prior to their admission to ICU. FINDING: The three patients presented with severe neurologic syndrome which included altered level of consciousness ranging from confusion to coma, ataxia, and focal motor deficit. Brain MRI revealed striking changes characterized by widespread, bilateral hyperintense lesions on T2-weighted imaging within the white matter and subcortical areas of the frontal, temporal, and parietal lobes, the basal ganglia, and corpus callosum. None of the lesions showed gadolinium enhancement. INTERPRETATION: CNS involvement should be considered in patients with MERS-CoV and progressive neurological disease, and further elucidation of the pathophysiology of this virus is needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s15010-015-0720-y) contains supplementary material, which is available to authorized users.


title: Hemogram data as a tool for decision-making in COVID-19 management: applications to resource scarcity scenarios

text: BACKGROUND: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity. PURPOSE: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. METHODS: Hemogram exams data from 510 symptomatic patients (73 positives and 437 negatives) were used to model and predict qRT-PCR results through Naïve-Bayes algorithms. Different scarcity scenarios were simulated, including symptomatic essential workforce management and absence of diagnostic tests. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context. RESULTS: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity, yielding a 100% sensitivity and 22.6% specificity with a prior of 0.9999; 76.7% for both sensitivity and specificity with a prior of 0.2933; and 0% sensitivity and 100% specificity with a prior of 0.001. Regarding background scarcity context, resources allocation can be significantly improved when model-based patient selection is observed, compared to random choice. CONCLUSIONS: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.


title: The effect of timing on community acquired respiratory virus infection mortality during the first year after allogeneic hematopoietic stem cell transplantation: a prospective epidemiological survey

text: The effect of timing of community acquired respiratory virus (CARV) infection after allogeneic hematopoietic stem cell transplant (allo-HCT) is an as yet unsettled issue. We evaluate this issue by including all consecutive allo-HCT recipients with molecularly-documented CARV infection during the first year after transplant. The study cohort was drawn from a prospective longitudinal survey of CARV in allo-HCT recipient having respiratory symptoms conducted from December 2013 to December 2018 at two Spanish transplant centers. Respiratory viruses in upper and/or lower respiratory specimens were tested using multiplex PCR panel assays. The study cohort comprised 233 allo-HCT recipients with 376 CARV infection episodes diagnosed during the first year after allo-HCT. Overall, 60% of CARV episodes occurred within the first 6 months (227 out of 376). Thirty patients (13%) had died at 3 months after CARV detection, of which 25 (83%) were recipients developing CARV within the first 6 months after transplant. Multivariate analysis identified four risk factors for mortality: ATG used as part of conditioning regimen [odds ratio (OR) 2.8, 95% confidence interval (C.I.) 1.21–6.4, p = 0.01], CARV lower respiratory tract disease (OR 3.4, 95% C.I. 1.4–8.4, p = 0.007), CARV infection within the first 6 months of transplant (OR 3.04, 95% C.I. 1.1–8.7, p = 0.03), and absolute lymphocyte count <0.2 × 109/L (OR 2.4, 95% C.I. 1–5.3, p = 0.04). Developing CARV infection within the first 6 months was associated with higher mortality. Our data supports that the timing of CARV development after allo-HCT could be of major interest.


title: Lessons from Hurricane Katrina for predicting the indirect health consequences of the COVID-19 pandemic

text: Beyond their immediate effects on mortality, disasters have widespread, indirect impacts on mental and physical well-being by exposing survivors to stress and potential trauma. Identifying the disaster-related stressors that predict health adversity will help officials prepare for the coronavirus disease 2019 (COVID-19) pandemic. Using data from a prospective study of young, low-income mothers who survived Hurricane Katrina, we find that bereavement, fearing for loved ones’ well-being, and lacking access to medical care and medications predict adverse mental and physical health 1 y postdisaster, and some effects persist 12 y later. Adjusting for preexisting health and socioeconomic conditions attenuates, but does not eliminate, these associations. The findings, while drawn from a demographically unique sample, suggest that, to mitigate the indirect effects of COVID-19, lapses in medical care and medication use must be minimized, and public health resources should be directed to those with preexisting medical conditions, their social networks, and the bereaved.


title: Impact of respiratory viruses in hospital-acquired pneumonia in the intensive care unit: A single-center retrospective study

text: Abstract Background Data on the frequency and role of respiratory viruses (RVs) in hospital-acquired pneumonia (HAP) are still scarce. Objectives We assessed the proportion of RVs and their impact on the outcome of hospital-acquired pneumonia (HAP) in the intensive care unit (ICU). Study design Cases of HAP were retrospectively selected among patients who underwent screening for RVs by multiplex PCR (mPCR) in the ICU of a French tertiary care hospital from May 2014 to April 2016. ICU length of stay and in-hospital mortality were compared between four groups defined according to the identified pathogens: virus only (V), virus/bacteria (V/B), bacteria only (B) and no pathogen (Neg). When available, previous mPCR was retrieved in order to assess possible chronic viral carriage. Results Overall, 95/999 (10%) ICU patients who underwent mPCR had HAP (V(17,18%), V/B(13,14%), B(60,63%), Neg(5,5%)). Median age was 61 years and 45 (47%) were immunocompromised. Influenza (27%) and rhinovirus (27%) were the most common RVs. V/B group had higher mortality rate than B and V groups (62% vs. 40% and 35%, p=0.3) and a significantly longer length of stay (31days (18–48)) than V group (5days (3–11), p=0.0002)) and B group (14.5days (5.5–25.5), p=0.007)). Among the 15 patients with available mPCR tests before viral HAP, seven were negative and eight were positive corresponding to long-term carriage of community-acquired viruses. Discussion RVs were detected in 32% of HAP patients who underwent mPCR. Two situations were encountered: (i) acute acquired viral infection; (ii) long-term viral carriage (mostly rhinovirus) especially in immunocompromised patients complicated by a virus/bacteria coinfection. The latter was associated with a longer length of stay and a trend toward a higher mortality.


Nature of the Virus Associated with Endemic Balkan Nephropathy


title: Viral interference between low pathogenic avian influenza H9N2 and avian infectious bronchitis viruses in vitro and in ovo

text: Abstract Background Low pathogenic avian influenza (LPAI) H9N2 and infectious bronchitis virus (IBV) are important pathogens of poultry, causing important economic losses for the sector. Replication interference between these two viruses was described using cell cultures (CC) and embryonated chicken eggs (ECE). Chicken embryo lung (CEL) and ECE were simultaneously or sequentially infected with IBV vaccine strain (H120) and LPAIV-H9N2 (A/Ck/TUN/145/2012) to evaluate viral interactionsin vitro and in ovo, respectively. Real-time RT-PCR was developed to specifically quantify both AIV and IBV genomes as well as viral gene copy numbers during mixed infections. The amount of IL-1 beta, in supernatants of co-infected cell cultures, was determined using an ELISA assay. Results Quantitative results of AIV and IBV co-infection showed that interferences between the two viruses yielded decreased viral growth. However, in the case of super-infection, the second virus, either AIV or IBV, induced a decrease in the growth of the first inoculated virus. Conclusion It appears that either AIV or IBV has a negative impact on the other virus growth when they are inoculated simultaneously or sequentially. The ELISA results showed that higher level of secreted IL-1beta varies, depending on the viral interference conditions between both viruses, during mixed infections.


‘COVID-19 Pandemic’ Anxiety induced Tako-tsubo Cardiomyopathy


title: Thermodynamic modeling of a novel air dehumidification system

text: Abstract A novel air dehumidification system is proposed. The proposed system incorporates a membrane-based total heat exchanger into a mechanical air dehumidification system, where the fresh air flows through the enthalpy exchanger, the evaporator and the condenser subsequently. Thermodynamic model for the performance estimation of the combined system is investigated. Processes of the fresh air and the refrigerant are studied. Two additional specific programs are devised to calculate the psychrometrics and the thermodynamic properties of the refrigerant R134a. Annual energy requirement is 4.15 × 106 kJ per person, or 33% saving from a system without energy saving measures.


title: Radiological findings of pneumonia in patients with swine-origin influenza A virus (H1N1)

text: PURPOSE: During spring 2009, a pandemic swine-origin influenza A (H1N1) virus (S-OIV) emerged and spread globally. We describe the chest X-ray and computed tomography (CT) findings of 40 patients with pneumonia due to S-OIV observed in our institution. MATERIAL AND METHODS: Among 534 patients with S-OIV, according to the US Centers for Disease Control and Prevention case definition, seen between June and November 2009, 121 underwent chest X-ray and 40 (median age 44 years, range 16–79) had pneumonia. The initial chest radiographs were evaluated for pattern, distribution and extent of lung abnormalities. Unenhanced chest CT scans were performed in two patients and were reviewed for the same findings. Underlying medical conditions were present in 42% of patients (17/40). RESULTS: Our patients had predominantly mild illness, and pneumonia was observed in 40 individuals (40/121 patients who had chest X-rays, 33%; and 40/534 patients with S-OIV, 7.5%). However, S-OIV can cause severe illness requiring admission to the intensive care unit for advanced mechanical ventilation and extracorporeal life support, including adult respiratory distress syndrome (ARDS) and death. The major radiological abnormalities observed were interstitial changes (60.0%), with (22.0%) or without patchy ground-glass appearance, mostly bilateral, and located in the lower lung zones (7.5%). Extensive disease was seen in 37.5% (15/40), and ARDS was observed in three individuals (0.30%)with underlying medical conditions. Subtle pleural effusion was noted in four patients. CONCLUSIONS: In our series, the most frequent pneumonia patterns observed during S-OIV (H1N1) virus were interstitial changes and patchy ground-glass appearance, mostly bilateral, and located in the lower lung zones. CT, performed in severely ill patients, confirmed the ARDS identified with chest X-rays, better depicting the features and extent of lung abnormalities.


title: Will the antimalarial drug take over to combat COVID-19?

text: BACKGROUND: China has been fighting the epidemic of pneumonia-like diseases first detected for over a month in the city of Wuhan in December 2019. The disease epidemic is caused by a novel coronavirus, called COVID-19, which has now infected more than 700,000 people worldwide. With a death toll approaching that of China’s SARS-CoV outbreak in 2002 and 2003, 2019-nCoV has contributed to an international emergency in public health, placing all health organizations on high alert. Such large numbers of infected and deceased people require an urgent need for reliable, inexpensive, and cheap drugs to control and reduce the outbreak. OBJECTIVE: To systematically review and evaluate the pattern of COVID-19 and the treatment plans. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The articles were searched from databases like PubMed, the Cochrane Library, ScienceDirect, and the Health Research and Development Information Network (HERDIN) combining MeSH and free-text terms. RESULTS: This analysis highlights the agent of COVID-19 and the possible transmission. The current research taking place to overcome this complex disease and the urgent need to develop improved therapeutics are also discussed. CONCLUSION: Herein, we present an epidemiological overview of the currently available information on the treatment claimed to have helped to bring the situation under control.


title: Modelling carbon mitigation pathways by 2050: Insights from the Global Calculator

text: Abstract The Global Calculator (GC) can be used to assess a wide range of climate change mitigation pathways. The GC is an accessible integrated model which calculates the cumulative emissions of a basket of the main greenhouse gases that result from a set of technological and lifestyle choices made at the global level and as defined by the user within a single system dynamics tool. Using the GC, we simulated ambitious scenarios against business as usual trends in order to stay below 2 °C and 1.5 °C of maximum temperature change by the end of this century and carried out a sensitivity analysis of the entire GC model option space. We show that the calculator is useful for making broad simulations for energy, carbon and land use dynamics, and demonstrate how combined and sustained mitigation efforts across different sectors are urgently needed to meet climate targets.


title: School attendance during a pandemic

text: When officials relax school attendance requirements as a prophylactic measure against a pandemic, students of higher prior performance take more absences, while students of lower prior performance keep going to school. Prior performance is positively associated with neighborhood income.


title: Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China

text: BACKGROUND: Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. METHODS: After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. RESULTS: Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P < 0.001). Attack rates increased with exposure time. CONCLUSIONS: Close contact and long exposure may have contributed to the transmission of 2009 H1N1 virus in the train. Trains may have played an important role in the 2009 influenza pandemic.


Omalizumab and COVID19 Treatment: Could It Help?


Giovanni Di Guardo: Animal models and pathogenetic insights to CoViD-19


title: Effect of experimental Ornithobacterium rhinotracheale infection along with live infectious bronchitis vaccination in broiler chickens

text: ABSTRACT Ornithobacterium rhinotracheale (ORT), a bacterium causing respiratory tract infection, has led to a significant problem in the intensive poultry production in Egypt. Polymerase chain reaction-amplified 784-bp specific ORT DNA fragments were found in 7 ORT isolates from lungs, air sacs, and tracheas of commercial broilers or layers in Egypt in 2015. The objective of this study was to investigate the role of the live variant IBV 4/91 with ORT infection. A total of 120 14-d-old broiler chickens (Cobb 500) were equally divided into 4 groups for experimental infection in a complete randomized design. Group 1 was infected with ORT strain and live infectious bronchitis vaccine (IBV 4/91) simultaneously; group 2 was infected with the bacterial strain alone; group 3 was vaccinated only with IBV 4/91, and group 4 was the non-vaccinated and non-infected control group. The respiratory signs, post-mortem lesions (tracheitis and pneumonia) and histopathological findings of lungs, trachea, and air sacs in the experimentally infected broiler chickens appeared to be more prominent in the chickens of group 1 than group 2. With respect to body weight, weight gain, feed conversion rate, and Ornithobacterium re-isolation, there was a difference (P ≤ 0.05) among the chickens of group 1 and the other groups. This reveals that the use of live infectious bronchitic vaccines, which is a common practice in the local Egyptian field of production, may concomitantly increase the pathogenicity of ORT in broiler chickens.


title: Inhibition of Henipavirus infection by RNA interference

text: Abstract Nipah virus (NiV) and Hendra virus (HeV) are recently emerged zoonotic paramyxoviruses exclusively grouped within a new genus, Henipavirus. These viruses cause fatal disease in a wide range of species, including humans. Both NiV and HeV have continued to re-emerge sporadically in Bangladesh and Australia, respectively. There are currently no therapeutics or vaccines available to treat Henipavirus infection and both are classified as BSL4 pathogens. RNA interference (RNAi) is a process by which double-stranded RNA directs sequence-specific degradation of messenger RNA in animal and plant cells. Small interfering RNAs (siRNAs) mediate RNAi by inhibiting gene expression of homologous mRNA and our preliminary studies suggest RNAi may be a useful approach to developing novel therapies for these highly lethal pathogens. Eight NiV siRNA molecules (four L and four N gene specific), two HeV N gene specific, and two non-specific control siRNA molecules were designed and tested for their ability to inhibit a henipavirus minigenome replication system (which does not require the use of live virus) in addition to live virus infections in vitro. In the minigenome assay three out of the four siRNAs that targeted the L gene of NiV effectively inhibited replication. In contrast, only NiV N gene siRNAs were effective in reducing live NiV replication, suggesting inhibition of early, abundantly expressed gene transcripts may be more effective than later, less abundant transcripts. Additionally, some of the siRNAs effective against NiV infection were only partially effective inhibitors of HeV infection. An inverse correlation between the number of nucleotide mismatches and the efficacy of siRNA inhibition was observed. The demonstration that RNAi effectively inhibits henipavirus replication in vitro, is a novel approach and may provide an effective therapy for these highly lethal, zoonotic pathogens.


title: A comparison study of realtime fatality rates: severe acute respiratory syndrome in Hong Kong, Singapore, Taiwan, Toronto and Beijing, China

text: Summary. In an outbreak of a completely new infectious disease like severe acute respiratory syndrome (SARS), estimation of the fatality rate over the course of the epidemic is of clinical and epidemiological importance. In contrast with the constant case fatality rate, a new measure, termed the ‘realtime’ fatality rate, is proposed for monitoring the new emerging epidemic at a population level. A competing risk model implemented via a counting process is used to estimate the realtime fatality rate in an epidemic of SARS. It can capture and reflect the time‐varying nature of the fatality rate over the course of the outbreak in a timely and accurate manner. More importantly, it can provide information on the efficacy of a certain treatment and management policy for the disease. The method has been applied to the SARS data from the regions affected, namely Hong Kong, Singapore, Toronto, Taiwan and Beijing. The magnitudes and patterns of the estimated fatalities are virtually the same except in Beijing, which has a lower rate. It is speculated that the effect is linked to the different treatment protocols that were used. The standard estimate of the case fatality rate that was used by the World Health Organization has been shown to be unable to provide useful information to monitor the time‐varying fatalities that are caused by the epidemic.


Delayed benign surgery during the COVID‐19 pandemic: the other side of the coin


title: Virtual screening identification of novel severe acute respiratory syndrome 3C-like protease inhibitors and in vitro confirmation

text: Abstract The 3C-like protease (3CLpro) of severe acute respiratory syndrome associated coronavirus (SARS-CoV) is vital for SARS-CoV replication and is a promising drug target. Structure based virtual screening of 308307 chemical compounds was performed using the computation tool Autodock 3.0.5 on a WISDOM Production Environment. The top 1468 ranked compounds with free binding energy ranging from −14.0 to −17.09kcalmol−1 were selected to check the hydrogen bond interaction with amino acid residues in the active site of 3CLpro. Fifty-three compounds from 35 main groups were tested in an in vitro assay for inhibition of 3CLpro expressed by Escherichia coli. Seven of the 53 compounds were selected; their IC50 ranged from 38.57±2.41 to 101.38±3.27μM. Two strong 3CLpro inhibitors were further identified as competitive inhibitors of 3CLpro with K i values of 9.11±1.6 and 9.93±0.44μM. Hydrophobic and hydrogen bond interactions of compound with amino acid residues in the active site of 3CLpro were also identified.


title: Babesiosis and blood transfusion: flying under the radar

text: Infectious agents of disease continue to plague transfusion medicine as an increasing number of pathogens are described that pose a potential blood safety risk. While the recent focus has been on newly emerged agents, several well‐established pathogens provide timely reminders that other agents continue to pose threats, but invariably ‘fly under the radar’, thereby failing to elicit adequate measures to prevent their transmission by blood transfusion. Perhaps foremost among this group of agents are the Babesia spp., which have been known to cause human disease, in the USA, for close to 40 years. B. microti, B. divergens and several Babesia‐like agents are responsible for a growing number of human babesiosis infections. Concomitantly, in the USA, there has been a sharp rise in the number of transfusion‐transmitted infections of Babesia spp., attributable almost exclusively to B. microti. Despite the obvious public health issues posed by Babesia spp., options for preventing their transmission by blood transfusion remain limited. However, recognition that the Babesia spp. are indeed an ongoing and expanding blood safety threat will probably prove instrumental in the development of viable interventions to limit transmission of these agents.