title: Functional Circularity of Legitimate Qβ Replicase Templates

text: Abstract Qβ replicase (RNA-directed RNA polymerase of bacteriophage Qβ) exponentially amplifies certain RNAs in vitro. Previous studies have shown that Qβ replicase can initiate and elongate on a variety of RNAs; however, only a minute fraction of them are recognized as ‘legitimate’ templates. Guanosine 5′-triphosphate (GTP)-dependent initiation on a legitimate template generates a stable replicative complex capable of elongation in the presence of aurintricarboxylic acid, a powerful inhibitor of RNA–protein interactions. On the contrary, initiation on an illegitimate template is GTP independent and does not result in the aurintricarboxylic-acid-resistant replicative complex. This article demonstrates that the 3′ and 5′ termini of a legitimate template cooperate during and after the initiation step. Breach of the cooperation by dividing the template into fragments or by introducing point mutations at the 5′ terminus reduces the rate and the yield of initiation, increases the GTP requirement, decreases the overall rate of template copying, and destabilizes the postinitiation replicative complex. These results revive the old idea of a functional circularity of legitimate Qβ replicase templates and complement the increasing body of evidence that functional circularity may be a common property of RNA templates directing the synthesis of either RNA or protein molecules.


title: Meeting the challenge of the 2019 novel coronavirus disease in patients with cancer

text: The alarming situation of the 2019 novel coronavirus disease (COVID‐19) is contrasted by the limited efforts to curb the spread and impact of the disease among patients with cancer. This commentary proposes a simple 5‐part strategy plus rapidly expanded use of telemedicine to anticipate and deal with COVID‐19 and, by extension, future epidemics in patients with cancer.


title: The orthopaedic and traumatology scenario during Covid-19 outbreak in Italy: chronicles of a silent war

text: BACKGROUND: From February 21, the day of hospitalisation in ICU of the first diagnosed case of Covid-19, the social situation and the hospitals’ organisation throughout Italy dramatically changed. METHODS: The CIO (Club Italiano dell’Osteosintesi) is an Italian society devoted to the study of traumatology that counts members spread in public and private hospitals throughout the country. Fifteen members of the CIO, Chairmen of 15 Orthopaedic and Trauma Units of level 1 or 2 trauma centres in Italy, have been involved in the study. They were asked to record data about surgical, outpatients clinics and ER activity from the 23rd of February to the 4th of April 2020. The data collected were compared with the data of the same timeframe of the previous year (2019). RESULTS: Comparing with last year, overall outpatient activity reduced up to 75%, overall Emergency Room (ER) trauma consultations up to 71%, elective surgical activity reduced up to 100% within two weeks and trauma surgery excluding femoral neck fractures up to 50%. The surgical treatment of femoral neck fractures showed a stable reduction from 15 to 20% without a significant variation during the timeframe. CONCLUSIONS: Covid-19 outbreak showed a tremendous impact on all orthopaedic trauma activities throughout the country except for the surgical treatment of femoral neck fractures, which, although reduced, did not change in percentage within the analysed timeframe.


title: Tracheostomy during COVID‐19 pandemic—Novel approach

text: BACKGROUND: This study describes a novel approach in reducing SARS‐CoV‐2 transmission during tracheostomy. METHODS: Five patients underwent tracheostomy between April 1, 2020 and April 17, 2020. A clear and sterile plastic drape was used as an additional physical barrier against droplets and aerosols. Operative diagnosis; droplet count and distribution on plastic sheet and face shields were documented. RESULTS: Tracheostomy was performed for patients with carcinoma of tonsil (n = 2) and nasopharynx (n = 1), and aspiration pneumonia (n = 2). Droplet contamination was noted on all plastic sheets (n = 5). Droplet contamination was most severe over the central surface at 91.5% (86.7%‐100.0%) followed by the left and right lateral surfaces at 5.2% (6.7%‐10.0%) and 3.3% (6.7%‐10.0%), respectively. No droplet contamination was noted on all face shields. CONCLUSION: Plastic drapes can help reduce viral transmission to health care providers during tracheostomy. Face shields may be spared which in turn helps to conserve resources during the novel coronavirus disease 2019 pandemic.


title: An Overview of Enzymatic Reagents for the Removal of Affinity Tags

text: Although they are often exploited to facilitate the expression and purification of recombinant proteins, every affinity tag, whether large or small, has the potential to interfere with the structure and function of its fusion partner. For this reason, reliable methods for removing affinity tags are needed. Only enzymes have the requisite specificity to be generally useful reagents for this purpose. In this review, the advantages and disadvantages of some commonly used endo- and exoproteases are discussed in light of the latest information.


Immunocytochemical Reorganization of the Nucleolus in Human Embryo Fibroblasts Infected with Cytomegalovirus in vitro


title: The Pandemic of Hate is Giving COVID-19 a Helping Hand

text: The Pandemic of Hate Is Giving Novel Coronavirus Disease (COVID-19) a Helping Hand.


title: Transparent Development of the WHO Rapid Advice Guidelines

text: Emerging health problems require rapid advice. We describe the development and pilot testing of a systematic, transparent approach used by the World Health Organization (WHO) to develop rapid advice guidelines in response to requests from member states confronted with uncertainty about the pharmacological management of avian influenza A (H5N1) virus infection. We first searched for systematic reviews of randomized trials of treatment and prevention of seasonal influenza and for non-trial evidence on H5N1 infection, including case reports and animal and in vitro studies. A panel of clinical experts, clinicians with experience in treating patients with H5N1, influenza researchers, and methodologists was convened for a two-day meeting. Panel members reviewed the evidence prior to the meeting and agreed on the process. It took one month to put together a team to prepare the evidence profiles (i.e., summaries of the evidence on important clinical and policy questions), and it took the team only five weeks to prepare and revise the evidence profiles and to prepare draft guidelines prior to the panel meeting. A draft manuscript for publication was prepared within 10 days following the panel meeting. Strengths of the process include its transparency and the short amount of time used to prepare these WHO guidelines. The process could be improved by shortening the time required to commission evidence profiles. Further development is needed to facilitate stakeholder involvement, and evaluate and ensure the guideline's usefulness.


Immunological aspects of grafting in the mammalian central nervous system. A review and speculative synthesis


title: Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung

text: Angiotensin converting enzyme (ACE) 2 is a carboxypeptidase that shares 42% amino acid homology with ACE. Little is known about the regulation or pattern of expression of ACE2 in the mouse lung, including its definitive cellular distribution or developmental changes. Based on Northern blot and RT‐PCR data, we report two distinct transcripts of ACE2 in the mouse lung and kidney and describe a 5′ exon 1a previously unidentified in the mouse. Western blots show multiple isoforms of ACE2, with predominance of a 75–80 kDa protein in the mouse lung versus a 120 kDa form in the mouse kidney. Immunohistochemistry localizes ACE2 protein to Clara cells, type II cells, and endothelium and smooth muscle of small and medium vessels in the mouse lung. ACE2 mRNA levels peak at embryonic day 18.5 in the mouse lung, and immunostaining demonstrates protein primarily in the bronchiolar epithelium at that developmental time point. In murine cell lines ACE2 is strongly expressed in the Clara cell line mtCC, as opposed to the low mRNA expression detected in E10 (type I‐like alveolar epithelial cell line), MLE‐15 (type II alveolar epithelial cell line), MFLM‐4 (fetal pulmonary vasculature cell line), and BUMPT‐7 (renal proximal tubule cell line). In summary, murine pulmonary ACE2 appears to be primarily epithelial, is developmentally regulated, and has two transcripts that include a previously undescribed exon. J. Cell. Biochem. 101:1278–1291, 2007. © 2007 Wiley‐Liss, Inc.


title: Cell-Surface Peptidases∗ ∗ Dedicated to Professor Dr. Eberhard Heymann on the occasion of his 65th birthday.

text: Abstract The cell surface has various functions: communicating with other cells, integrating into the tissue, and interacting with the extracellular matrix. Proteases play a key role in these processes. This review focuses on cell-surface peptidases (ectopeptidases, oligopeptidases) that are involved in the inactivation or activation of extracellular regulatory peptides, hormones, paracrine peptides, cytokines, and neuropeptides. The nomenclature of cell-surface peptidases is explained in relation to other proteases, and information is provided on membrane anchoring, catalytic sites, regulation, and, in particular, on their physiological and pharmacological importance. Furthermore, nonenzymatic (binding) functions and participation in intracellular signal transduction of cell surfaces peptidases are described. An overview on the different cell-surface peptidases is given, and their divergent functions are explained in detail. An example of actual pharmacological importance, dipeptidyl-peptidase IV (CD26), is discussed.


Novel Method to Expedite Early Healing of Dental Implant


title: Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19)

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.


Follow-up of caregivers involved in the management of COVID-19


title: CD56+ B-cell Neurolymphomatosis in a Cat

text: Summary A 16-year-old male Russian blue cat was presented with acute onset of paraparesis of the forelimbs that progressed to tetraparesis. Neurological examination revealed non-ambulatory tetraparesis with decreased postural reactions in all four limbs. Magnetic resonance imaging revealed multifocal nerve root swelling on the right at C6/C7 and C7/T1, while ultrasonography demonstrated swelling of the right brachial plexus. To understand the cause of the nerve swelling, the right musculocutaneous nerve arising from the brachial plexus and the pectoralis muscle were biopsied. Histologically, there was evidence of neurolymphomatosis (neurotropic lymphoma) with Wallerian degeneration and denervation atrophy of myofibres. The neoplastic lymphoid cells expressed CD79a, CD20 and CD56. Based on these findings, a diagnosis of B-cell neurolymphomatosis was made. Expression of CD56, synonymous with neural cell adhesion molecule, is rare in B-cell lymphomas and has not been reported in feline B-cell lymphomas or feline neurolymphomatosis. CD56 expression was suspected to have played an important role in neurotropism of the neoplastic cells in this case.


title: Guidance for anti-VEGF intravitreal injections during the COVID-19 pandemic

text: PURPOSE: There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection. METHODS: The Vision Academy’s Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance. RESULTS: The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring. CONCLUSION: Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.


title: Development and Characterization of Broadly Cross-reactive Monoclonal Antibodies Against All Known Ebolavirus Species

text: As of 25 March 2015, the largest recorded outbreak of Ebola virus infection is ongoing, with almost 25 000 cases and >10 000 deaths. There are 5 genetically and antigenically distinct species within the genus Ebolavirus. Limited cross-reactivity and protection is observed between these 5 Ebolavirus species, which complicates vaccine development. However, on the basis of sequence homology between the 5 Ebolavirus species, we hypothesize that conserved epitopes are present on the viral glycoprotein (GP), which can be targeted by antibodies. In the current study, a panel of mouse monoclonal antibodies was isolated and characterized using an enzyme-linked immunosorbent assay (ELISA) to determine cross-reactivity, avidity, and competition for epitope binding; Western blot analysis was also performed. Four monoclonal antibodies were identified by ELISA as cross-reacting with the GPs of all 5 Ebolavirus species. The identification of cross-reactive antibodies that bind the GPs of all known Ebolavirus species will give us important insight into the presence of conserved epitopes on the viral GP. These data will be crucial for the development of novel therapeutics and diagnostic assays.


Official Data and Analytical Forecasts: Differences and Similarities Among Coronavirus Disease (COVID-19) Confirmed Cases and Deaths


The VACCINES Act, Deciphering Vaccine Hesitancy in the Time of COVID19


title: Transcriptogram analysis reveals relationship between viral titer and gene sets responses during Corona-virus infection.

text: To understand the difference between benign and severe outcomes after Coronavirus infection, we urgently need ways to clarify and quantify the time course of tissue and immune responses. Here we re-analyze 72-hour time-series microarrays generated in 2013 by Sims and collaborators for SARS-CoV-1 in vitro infection of a human lung epithelial cell line. Using a Transcriptogram-based top-down approach, we identified three major, differentially-expressed gene sets comprising 219 mainly immune-response-related genes. We identified timescales for alterations in mitochondrial activity, signaling and transcription regulation of the innate and adaptive immune systems and their relationship to viral titer. At the individual-gene level, EGR3 was significantly upregulated in infected cells. Similar activation in T-cells and fibroblasts in infected lung could explain the T-cell anergy and eventual fibrosis seen in SARS-CoV-1 infection. The methods can be applied to RNA data sets for SARS-CoV-2 to investigate the origin of differential responses in different tissue types, or due to immune or preexisting conditions or to compare cell culture, organoid culture, animal models and human-derived samples.


title: Severe Cardiac Dysfunction in a Patient with Multisystem Inflammatory Syndrome in Children Associated with COVID-19: Retrospective Diagnosis of a Puzzling Presentation. A Case Report

text: Abstract We report one of the earliest known U.S. cases of multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). This adolescent male presented prior to any known association between COVID-19 and immune mediated inflammatory syndrome in children. He presented in stable condition and without significant multisystem involvement. During hospitalization he developed severe left ventricular dysfunction and mixed hypovolemic, distributive and cardiogenic shock. Clinical features overlapped with Kawasaki disease, acute rheumatic fever, and toxic shock syndrome. After centers in Europe began reporting a multisystem inflammatory condition in children with COVID-19, the patient’s clinical course and laboratory findings were revisited. He underwent newly available antibody testing and was diagnosed as one of the first known cases of MIS-C in the United States.


title: A specific transmembrane domain of a coronavirus E1 glycoprotein is required for its retention in the Golgi region

text: The E1 glycoprotein of the avian coronavirus infectious bronchitis virus contains a short, glycosylated amino-terminal domain, three membrane-spanning domains, and a long carboxy-terminal cytoplasmic domain. We show that E1 expressed from cDNA is targeted to the Golgi region, as it is in infected cells. E1 proteins with precise deletions of the first and second or the second and third membrane-spanning domains were glycosylated, thus suggesting that either the first or third transmembrane domain can function as an internal signal sequence. The mutant protein with only the first transmembrane domain accumulated intracellularly like the wild-type protein, but the mutant protein with only the third transmembrane domain was transported to the cell surface. This result suggests that information specifying accumulation in the Golgi region resides in the first transmembrane domain, and provides the first example of an intracellular membrane protein that is transported to the plasma membrane after deletion of a specific domain.


title: Identification of two antigenic epitopes on SARS-CoV spike protein

text: Abstract The spike (S) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a major virion structural protein. It plays an important role in interaction with receptor and inducing neutralizing antibodies. In the study, six tentative antigenic epitopes (S1 S2 S3 S4 S5 S6) of the spike protein of SARS-CoV were predicted by bio-informatics analysis, and a multi-epitope chimeric gene of S1–S2–S3–S4–S5–S6 was synthesized and fused to downstream GST gene in pGEX-6p-1. The Western blotting demonstrated that SARS patient convalescent serum could recognize the recombinant fusion protein. A number of monoclonal antibodies were developed against the fusion protein. In further, the six predicted epitope genes were individually fused to GST of pGEX-6p-1 and expressed in Escherichia coli BL21, respectively. Among six fusion peptides, S5 reacted with monoclonal antibody D3C5 and S2 reacted with monoclonal antibody D3D1 against spike protein of SARS-CoV. The epitopes recognized by monoclonal antibodies D3C5 and D3D1 are linear, and correspond to 447–458 and 789–799 amino acids of spike protein of SARS-CoV, respectively. Identification of antigenic epitope of spike protein of SARS-CoV could provide the basis for the development of immunity-based prophylactic, therapeutic, and diagnostic techniques for the control of severe acute respiratory syndrome.


title: Identifying very low-risk STEMI patients for early ICU discharge in the COVID-19 era

text: Objectives To perform an online survey aimed at evaluating the impact of COVID-19 on Italian radiology departments Methods We launched a survey composed of 25 questions about how COVID-19 has changed the safety and organization of daily activity in Italian radiology units Results A total of 2136/10,564 (20 2%) radiologists of the Italian Society of Medical and Interventional Radiology participated Two-thirds performed at least one diagnostic/interventional procedure on COVID-19 patients The 88 1% reported a reduction in the elective imaging volumes, with US, mammography, and MRI having shown the greater decrease (41 1%, 23 9%, and 21 1%, respectively) In 69 6% of cases, institutions had trouble getting personal protective equipment (PPE), especially public hospitals and southern institutions Less than 30% of participants were subjected to RT-PCR swab test, although 81 5% believed that it should be done on all health workers and 70% suggested it as the most important measure to improve safety at work Slightly more than half of participants declared to work safely and felt to be adequately protected by their institutions Up to 20% of northern participants were redeployed to clinical services The first imaging examination performed by admitted COVID-19 patients was chest radiography in 76 3% of cases Almost half of participants reported that less than 30% of health workers were infected in their radiology department, with higher rates in northern regions and public institutions Conclusions This snapshot of the current situation in Italian radiology departments could be used to harmonize the organization of working activity in order to safely and effectively face this pandemic Key Points • More than two-thirds of institutions had trouble getting PPE for health workers, with public hospitals and southern institutions that presented more procurement problems • A substantial drop of imaging volumes was observed in the vast majority of Italian radiology departments, mostly due to the decrease of ultrasound, mammography, and MRI, especially in private practice were working activity was stopped in 13 3% of institutions • RT-PCR swab to health workers was reported as the most suggested measure by Italian radiologists to improve safety at work, as more than 80% of them believed that it should be performed to all health workers, although less than 30% were subjected to this test


title: Respiratory viruses, a common microbiological finding in neutropenic children with fever

text: Abstract Background Febrile neutropenia is a common complication in children undergoing chemotherapy for malignancies. A microbial agent is only identified in 15–30% of the fever episodes and corresponds mostly to bacterial findings. Objective To investigate viral infections as possible etiologic agents in episodes of febrile neutropenia. Study design Nasopharyngeal aspirates (NPAs) from patients presenting with neutropenic fever at two pediatric oncology wards in Sweden and Australia were analyzed with a conventional virus-diagnostic approach and RT-PCR. Coupled blood samples were analyzed for the detection of CMV, EBV, adenovirus and erythrovirus. Bacterial blood culture was performed routinely. Results Conventional virus-diagnostic approach coupled to routinely performed bacterial analyzes revealed an infectious agent in 29% compared to 60% when using PCR. By adding PCR, a viral pathogen was detected in 46% of the NPAs and in 4% of the blood samples collected. In half of the patients with bacteremia, respiratory tract viruses were co-detected. Conclusion Respiratory viruses were frequently detected in NPAs suggesting a significant role of viral infections in children presenting with neutropenic fever. The meaning of these findings needs to be further evaluated but has the potential to individualize infection treatment and to reduce the extensive use of antibiotics in immunocompromised children with neutropenia.


title: Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development

text: Vaccines based on virus-like particles have proved their success in human health. More than 25 years after the approval of the first vaccine based on this technology, the substantial efforts to expand the range of applications and target diseases are beginning to bear fruit. The incursion of high-throughput screening technologies, combined with new developments in protein engineering and chemical coupling, have accelerated the development of systems capable of producing macrostructures useful for vaccinology, gene delivery, immunotherapy and bionanotechnology. This review summarizes the most recent developments in microbial cell factories and cell-free systems for virus-like particle production and discusses the future impact of this technology in human and animal health.


title: Effect of human movement on airborne disease transmission in an airplane cabin: study using numerical modeling and quantitative risk analysis

text: BACKGROUND: Airborne transmission of respiratory infectious disease in indoor environment (e.g. airplane cabin, conference room, hospital, isolated room and inpatient ward) may cause outbreaks of infectious diseases, which may lead to many infection cases and significantly influences on the public health. This issue has received more and more attentions from academics. This work investigates the influence of human movement on the airborne transmission of respiratory infectious diseases in an airplane cabin by using an accurate human model in numerical simulation and comparing the influences of different human movement behaviors on disease transmission. METHODS: The Eulerian–Lagrangian approach is adopted to simulate the dispersion and deposition of the expiratory aerosols. The dose–response model is used to assess the infection risks of the occupants. The likelihood analysis is performed as a hypothesis test on the input parameters and different human movement pattern assumptions. An in-flight SARS outbreak case is used for investigation. A moving person with different moving speeds is simulated to represent the movement behaviors. A digital human model was used to represent the detailed profile of the occupants, which was obtained by scanning a real thermal manikin using the 3D laser scanning system. RESULTS: The analysis results indicate that human movement can strengthen the downward transport of the aerosols, significantly reduce the overall deposition and removal rate of the suspended aerosols and increase the average infection risk in the cabin. The likelihood estimation result shows that the risk assessment results better fit the outcome of the outbreak case when the movements of the seated passengers are considered. The intake fraction of the moving person is significantly higher than most of the seated passengers. CONCLUSIONS: The infection risk distribution in the airplane cabin highly depends on the movement behaviors of the passengers and the index patient. The walking activities of the crew members and the seated passengers can significantly increase their personal infection risks. Taking the influence of the movement of the seated passengers and the index patient into consideration is necessary and important. For future studies, investigations on the behaviors characteristics of the passengers during flight will be useful and helpful for infection control. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-434) contains supplementary material, which is available to authorized users.


title: Cloning and characterization of a tyrosine decarboxylase involved in the biosynthesis of galanthamine in Lycoris aurea

text: BACKGROUND: Galanthamine, one kind of Amaryllidaceae alkaloid extracted from the Lycoris species, is used in the treatment of Alzheimer’s disease. In regards to medical and economic importance, the biosynthesis and regulatory mechanism of the secondary metabolites in Lycoris remain uninvestigated. METHODS: BLAST was used to identify the sequence of tyrosine decarboxylase in the transcriptome of Lycoris aurea (L’Hér) Herb. The enzyme activity of this TYDC was determined by using heterologous expressed protein in the Escherichia coli cells. The related productive contents of tyramine were detected using High Performance Liquid Chromatography (HPLC). According to the available micro RNA sequencing profiles and degradome database of L. aurea, microRNA396 were isolated, which targets to LaTYDC1 and RNA Ligase-Mediated-Rapid Amplification of cDNA Ends (RLM-RACE) were used to confirm the cleavage. The expression levels of miR396 and LaTYDC1 were measured using a quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: LaTYDC1 was mainly expressed in root, bulb, leaf and flower fitting the models for galanthamine accumulation. This decarboxylase efficiently catalyzes tyrosine to tyramine conversion. Under methyl jasmonate (MeJA) treatment, the expression of LaTYDC1 and the content of tyramine sharply increase. The use of RLM-RACE confirms that miR396 promotes the degradation of LaTYDC1 mRNA. Under MeJA treatment, the expression of miR396 was suppressed while the expression level of LaTYDC1 sharply increased. Following the increase of the miR396 transcriptional level, LaTYDC1 was significantly repressed. CONCLUSION: LaTYDC1 participates in the biosynthesis of galanthamine, and is regulated by miR396. This finding also provides genetic strategy for improving the yield of galanthamine in the future.


title: MERS coronavirus envelope protein has a single transmembrane domain that forms pentameric ion channels

text: Abstract The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly identified pathogen able of human transmission that causes a mortality of almost 40%. As in the case of SARS-CoV, MERS virus lacking E protein represents a potential vaccine. In both cases, abolishment of channel activity may be a contributor to the attenuation observed in E-deleted viruses. Herein, we report that purified MERS-CoV E protein, like SARS-CoV E protein, is almost fully α-helical, has a single α-helical transmembrane domain, and forms pentameric ion channels in lipid bilayers. Based on these similarities, and the proposed involvement of channel activity as virulence factor in SARS-CoV E protein, MERS-CoV E protein may constitute a potential drug target.


title: Predictions of Systemic, Intracellular, and Lung Concentrations of Azithromycin with Different Dosing Regimens used in COVID‐19 Clinical Trials

text: Azithromycin, a broad‐spectrum macrolide antibiotic, is being investigated in patients with COVID‐19. A population pharmacokinetic model was implemented to predict lung, intracellular poly/mononuclear cell (PBM/PML), and alveolar macrophage (AM) concentrations using published data and compared against preclinical EC90 for SARS‐CoV‐2. The final model described the data reported in 8 publications adequately. Consistent with its known properties, concentrations were higher in AM and PBM/PML, followed by lung tissue, and lowest systemically. Simulated PBM/PML concentrations exceeded EC90 following the first dose and for approximately 14 days following 500 mg QD for 3 days or 500 mg QD for 1 day/250 mg QD on days 2‐5, 10 days following a single 1000 mg dose, and for more than 20 days with 500 mg QD for 10 days. AM concentrations exceeded the IC90 for more than 20 days for all regimens. These data will better inform optimization of dosing regimens for azithromycin clinical trials.


title: Advances in Developing Therapies to Combat Zika Virus: Current Knowledge and Future Perspectives

text: Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and molecular investigations are underway to investigate ZIKV pathology and its recent enhanced pathogenicity, as well as to design safe and potent vaccines, drugs, and therapeutics. This review describes progress in the design and development of various anti-ZIKV therapeutics, including drugs targeting virus entry into cells and the helicase protein, nucleosides, inhibitors of NS3 protein, small molecules, methyltransferase inhibitors, interferons, repurposed drugs, drugs designed with the aid of computers, neutralizing antibodies, convalescent serum, antibodies that limit antibody-dependent enhancement, and herbal medicines. Additionally, covalent inhibitors of viral protein expression and anti-Toll-like receptor molecules are discussed. To counter ZIKV-associated disease, we need to make rapid progress in developing novel therapies that work effectually to inhibit ZIKV.


title: Diagnostic microbiologique : du diagnostic par étiologie au diagnostic par syndrome

text: Résumé Objectifs Depuis les dix dernières années, l’introduction de la biologie moléculaire et l’automatisation ont radicalement changé les pratiques dans les laboratoires de microbiologie clinique. L’amélioration de la communication entre les microbiologistes et les cliniciens ainsi que les évolutions technologiques telles que la standardisation et le développement de tests diagnostics plus rapides ont conduit à une réorganisation des laboratoires de microbiologie. Méthodes Jusqu’à présent la prescription des examens ciblait un diagnostic étiologique précis, actuellement l’évolution se fait vers le diagnostic par syndrome incluant un panel de tests regroupant les étiologies responsables d’un syndrome donné y compris les pathogènes émergents. Résultats et conclusions Dans cette revue, nous avons résumé les développements technologiques les plus récents en matière de diagnostic microbiologique adapté au diagnostic par syndrome incluant les stratégies de diagnostic exhaustif, les DNA microarray et les microarray antigéniques. Summary Objectives Over the past decade, the introduction of techniques of molecular biology and the automation have undergone important changes in the practice of clinical microbiological laboratories. Methods Commonly, physician prescriptions are etiology driven for emerging infectious agent. The improving in test standardization and rapidity and the best communication between physician and clinical microbiologist lead to profound changes in microbiology laboratories. Results and conclusion The present review summarizes the recent development in multiplexed microbiological technology adapted to syndrome driven diagnosis, including sampling strategy, DNA microarray and antigenic microarray.


title: Enter the kill zone: Initiation of death signaling during virus entry

text: Abstract Infection of host cells by a variety of viruses results in programmed cell death or apoptosis. In many cases, early events in virus replication that occur prior to synthesis of viral proteins and replication of viral genomes directly or indirectly activate signaling pathways that culminate in cell death. Using examples of viruses for which prodeath signaling is better defined, this review will describe how cell entry steps including virus attachment to receptors, virus uncoating in endosomes, and events that occur following membrane penetration lead to apoptosis. The relevance and physiologic consequences of early induction of prodeath signaling to viral pathogenesis also will be discussed.


title: Over-expression of severe acute respiratory syndrome coronavirus 3b protein induces both apoptosis and necrosis in Vero E6 cells

text: Abstract The genome of the severe acute respiratory syndrome coronavirus encodes for eight accessory viral proteins with no known homologues in other coronaviruses. One of these is the 3b protein, which is encoded by the second open reading frame in subgenomic RNA 3 and contains 154 amino acids. Here, a detailed time-course study was performed to compare the apoptosis and necrosis profiles induced by full-length 3b, a 3b mutant that was deleted by 30 amino acids from the C terminus (3bΔ124-154) and the classical apoptosis inducer, Bax. Our results showed that Vero E6 cells transfected with a construct for expressing 3b underwent necrosis as early as 6h after transfection and underwent simultaneous necrosis and apoptosis at later time-points. At all the time-points analysed, the apoptosis induced by the expression of 3b was less than the level induced by Bax but the level of necrosis was comparable. The 3bΔ124-154 mutant behaves in a similar manner indicating that the localization of the 3b protein does not seems to be important for the cell-death pathways since full-length 3b is localized predominantly to the nucleolus, while the mutant is found to be concentrated in the peri-nuclear regions. To our knowledge, this is the first report of the induction of necrosis by a SARS-CoV protein.


title: Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

text: Viral infections affect three to five million patients annually. While commonly used antivirals often show limited efficacy and serious adverse effects, herbal extracts have been in use for medicinal purposes since ancient times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may be a proper alternative for treating viral diseases. With that in mind, various pharmaceutical formulations and delivery systems including micelles, nanoparticles, nanosuspensions, solid dispersions, microspheres and crystals, self-nanoemulsifying and self-microemulsifying drug delivery systems (SNEDDS and SMEDDS) have been developed and used for antiviral delivery of natural products. These diverse technologies offer effective and reliable delivery of medicinal phytochemicals. Given the challenges and possibilities of antiviral treatment, this review provides the verified data on the medicinal plants and related herbal substances with antiviral activity, as well as applied strategies for the delivery of these plant extracts and biologically active phytochemicals. [Figure: see text]


title: Outcome of patients with meticillin-resistant Staphylococcus aureus bacteraemia at an emergency department of a medical centre in Taiwan

text: Abstract The number of patients presenting to the Emergency Department (ED) with meticillin-resistant Staphylococcus aureus (MRSA) is increasing, but few studies focus on patients with bacteraemia. From January 2001 to June 2006 the clinical characteristics and outcome of 177 consecutive patients with MRSA bacteraemia visiting an ED of a university hospital were studied. The average age of the patients was 65.8 years. Healthcare-associated MRSA bacteraemia comprised 76.3% of all cases. Catheter-related bacteraemia was the most common type of infection (22.6%), followed by soft tissue infection (20.9%) and primary bacteraemia (15.3%). Different types of infection were significantly related to different outcome. In-hospital mortality was 33.3%, but the mortality decreased to 17.7% when patients with rapidly fatal disease and mortality within 3 days were excluded. All isolates exhibited lower susceptibility to vancomycin (minimum inhibitory concentration (MIC) 1–2μg/mL). Factors associated with mortality included severity of underlying illness, severity of bacteraemia and persistent bacteraemia. A detrimental effect of elevated MIC could not be demonstrated despite applying several definitions of patient outcome. Patients admitted to the ED with MRSA bacteraemia carry high overall mortality; however, the severity of underlying illness, severity of bacteraemia and persistent bacteraemia are correlated with mortality, but not vancomycin MICs (2μg/mL) of MRSA isolates.


title: COVID-19: Global radiation oncology’s targeted response for pandemic preparedness

text: Abstract As the global COVID-19 pandemic escalates there is a need within radiation oncology to work to support our patients in the best way possible. Measures are required to reduce infection spread between patients and within the workforce. Departments need contingency planning to create capacity and continue essential treatments despite a reduced workforce. The #radonc community held an urgent online journal club on Twitter in March 2020 to discuss these issues and create some consensus on crucial next steps. There were 121 global contributors. This document summarises these discussions around themes of infection prevention, rationalisation of workload and working practice in the presence of infection.


title: Does the Room Sharing Business Model Disrupt Housing Markets? Empirical Evidence of Airbnb in Taiwan

text: Recent research interest has focused on the impact of the room sharing business model on housing markets. However, existing empirical evidence is limited and exclusively focuses on few large cities in the U.S. This study examines the effects of Airbnb on housing rental and sales prices using a unique large-scale dataset comprised of housing market transaction records and the number of Airbnb listings drawn from their website in Taiwan. We estimate a fixed effect model of housing rental and sales price equations and find that a one-standard deviation increase in the number of Airbnb listings raises house rental prices by 0.38%. This finding suggests that a substitution effect is present between Airbnb's short-term accommodation and the housing rental market. Moreover, a larger effect on rental price is found among Airbnb listings that offer an entire room or apartment. Additionally, since September 2017, multinational digital platform companies must comply with a new sales tax policy in Taiwan. We evaluate the effect of this tax policy using the difference-in-difference method and find a negative impact on the number of Airbnb listings and housing rental prices after its implementation. This study is the first to empirically assess the effectiveness of tax policy on regulating room sharing business models.


title: Recommendations for the prevention and treatment of the novel coronavirus pneumonia in the elderly in China

text: The population is commonly susceptible to the 2019 novel coronavirus (2019‐nCoV), especially the elderly with comorbidities. Elderly patients infected with 2019‐nCoV tend to have higher rates of severe illness and mortality. Immunosenescence is an important cause of severe novel coronavirus pneumonia (NCP) in the elderly. Due to the combination of underlying diseases, elderly patients may exhibit atypical manifestations in clinical symptoms, supplementary examinations, and pulmonary imaging, deserving particular attention. The general condition of the elderly should be considered during diagnosis and treatment. In addition to routine care and measures—such as oxygen therapy, antiviral therapy, and respiratory support—treatment of underlying disease, nutritional support, sputum expectoration complication prevention, and psychological support should also be considered for elderly patients. Based on a literature review and expert panel discussion, we drafted the "Recommendations for the Prevention and Treatment of the Novel Coronavirus Pneumonia in the elderly in China," aiming to provide help with the prevention and treatment of NCP and the reduction of harm to the elderly population.


title: Adjunctive therapies and immunomodulatory agents in the management of severe influenza

text: Abstract In addition to neuraminidase inhibitors and other drugs that directly target viral replication, a number of adjunctive and immunomodulatory therapies are currently under evaluation for the treatment of influenza. These novel treatments, which focus either on pathophysiological aspects of influenza virus infection or the neutralization of virus with antibodies, are the subject of this review. Cytokine dysregulation has been observed in patients with severe influenza, such as avian influenza A (H5N1) and pandemic 2009 influenza A (H1N1pdm09) virus infections, but the role of immunomodulatory therapy is unclear, due to lack of data from randomized controlled trials (RCTs). Convalescent plasma appears to be useful as an adjunctive therapy for the treatment of H5N1 and H1N1pdm09 infections. Until lately, data interpretation was limited to case reports and studies of non-randomized design, but a recent RCT found that patients with severe influenza A (H1N1pdm09) who were treated with hyperimmune immunoglobulin from persons who had survived the same disease had a lower peak viral load and lower mortality than controls, providing treatment was begun within 5days of symptom onset. The efficacy of agents with potential immunomodulating effects, including intravenous immunoglobulin, N-acetylcysteine, acute use of statins, macrolides, peroxisome proliferator-activated receptors agonists, celecoxib and mesalazine, and the role of plasmapheresis and hemoperfusion as rescue therapy, deserve more investigation and where feasible, studies by RCTs. Prospective observational studies have shown that systemic corticosteroids increase morbidity (e.g., secondary infections) and mortality in H1N1pdm09 influenza. This article forms part of a symposium in Antiviral Research on “Treatment of influenza: targeting the virus or the host.”


title: Chapter 18 Electrochemical virus detections with nanobiosensors

text: Abstract Infectious diseases are caused from pathogens, which need a reliable and fast diagnosis. Today, expert personnel and centralized laboratories are needed to afford much time in diagnosing diseases caused from pathogens. Recent progress in electrochemical studies shows that biosensors are very simple, accurate, precise, and cheap at virus detection, for which researchers find great interest in this field. The clinical levels of these pathogens can be easily analyzed with proposed biosensors. Their working principle is based on affinity between antibody and antigen in body fluids. The progress still continues on these biosensors for accurate, rapid, reliable sensors in future.


title: New method for global alignment of 2 DNA sequences by the tree data structure

text: Abstract We introduce a new approach to investigate problem of DNA sequence alignment. The method consists of three parts: (i) simple alignment algorithm, (ii) extension algorithm for largest common substring, (iii) graphical simple alignment tree (GSA tree). The approach firstly obtains a graphical representation of scores of DNA sequences by the scoring equation R 0 * R − S 0 * S − T 0 * ( a + bk ) . Then a GSA tree is constructed to facilitate solving the problem for global alignment of 2 DNA sequences. Finally we give several practical examples to illustrate the utility and practicality of the approach.


title: Influenza: Critique of the contemporary challenges for pandemic planning, prevention, control, and treatment in emergency health services

text: Summary The 2009 H1N1 influenza pandemic was a major challenge to health services around the world. Previous experiences with Severe Acute Respiratory Syndrome (SARS) and Avian Influenza A (H5N1) prompted initiation of formal pandemic planning. Essential and desirable features of pandemic plans include preparation for surveillance, investigation of cases, treatment modalities, prevention of community spread, maintenance of essential services, research and evaluation, and implementation, testing and revision of the plan. The experience of 2009 H1N1 influenza pandemic for emergency departments and their staff was problematic. The pace of the pandemic, coupled with untested pandemic plans, presented a unique range of challenges. In this paper, the contemporary challenges with respect to pandemic influenza prevention, control, and treatment are examined. The lessons learned are critical to our response to future pandemics, which are inevitable.


Time to revisit uneven policy in the US for medication for opioid use disorder during Covid19


title: BioTorrents: A File Sharing Service for Scientific Data

text: The transfer of scientific data has emerged as a significant challenge, as datasets continue to grow in size and demand for open access sharing increases. Current methods for file transfer do not scale well for large files and can cause long transfer times. In this study we present BioTorrents, a website that allows open access sharing of scientific data and uses the popular BitTorrent peer-to-peer file sharing technology. BioTorrents allows files to be transferred rapidly due to the sharing of bandwidth across multiple institutions and provides more reliable file transfers due to the built-in error checking of the file sharing technology. BioTorrents contains multiple features, including keyword searching, category browsing, RSS feeds, torrent comments, and a discussion forum. BioTorrents is available at http://www.biotorrents.net.


title: Efficacy of inactivated variant porcine epidemic diarrhea virus vaccines in growing pigs

text: PURPOSE: The first aim of this study was to develop a novel inactivated porcine epidemic diarrhea virus (PEDV) vaccine using the recently isolated Korean PEDV QIAP1401 strain and to evaluate its protective efficacy in growing pigs. The second was to determine the optimum adjuvant formulation of the inactivated PEDV vaccine that induces protection against viral challenge. MATERIALS AND METHODS: To generate high titers of infectious PEDV, the QIAP1401 isolate was passaged in Vero cells. The experimental vaccines were prepared from a binary ethyleneimine-inactivated QIAP1401 strain passaged sequentially 70 times (QIAP1401-p70), formulated with four commercial adjuvants, and administered twice intramuscularly to growing pigs. Challenge studies using a virulent homologous strain of PEDV QIAP1401-p11, which was passaged 11 times after isolation, were performed to assess protection against disease progression and viral shedding during the 15-day observation period. The vaccine-induced antibody responses were measured in serum samples collected at predetermined time points by indirect enzyme-linked immunosorbent assay and virus neutralization test. RESULTS: The QIAP1401-p70 strain had 42 amino acid (aa) mutations, including a 25 aa deletion, and was selected as the inactivated PEDV vaccine candidate. Although none of the pigs that received the experimental vaccines were completely protected against subsequent viral challenge, they exhibited a significantly higher immune response than did non-vaccinated control pigs. Among the vaccine groups, the highest antibody responses were observed in the pigs that received an oil-based multiphasic water/oil/water (W/O/W) emulsion adjuvanted vaccine, which delayed the onset of clinical symptoms and viral shedding. CONCLUSION: A novel inactivated PEDV vaccine formulated with a W/O/W emulsion adjuvant was both immunogenic and protective against viral challenge.


docid: ltwyxyar

title: Effect of Early Enteral Nutrition on Intestinal Permeability, Intestinal Protein Loss, and Outcome in Dogs with Severe Parvoviral Enteritis

text: A randomized, controlled clinical trial investigated the effect of early enteral nutrition (EN) on intestinal permeability, intestinal protein loss, and outcome in parvoviral enteritis. Dogs were randomized into 2 groups: 15 dogs received no food until vomiting had ceased for 12 hours (mean 50 hours after admission; NPO group), and 15 dogs received early EN by nasoesophageal tube from 12 hours after admission (EEN group). All other treatments were identical. Intestinal permeability was assessed by 6‐hour urinary lactulose (L) and rhamnose (R) recoveries (%L, %R) and L/R recovery ratios. Intestinal protein loss was quantified by fecal α(1)‐proteinase inhibitor concentrations (α(1)‐PI). Median time to normalization of demeanor, appetite, vomiting, and diarrhea was 1 day shorter for the EEN group for each variable. Body weight increased insignificantly from admission in the NPO group (day 3: 2.5±2.8% day 6: 4.3±2.3% mean ± SE), whereas the EEN group exhibited significant weight gain (day 3: 8.1±2.7% day 6: 9.7 ± 2.1%). Mean urinary %L was increased, %R reduced, and L/R recovery ratios increased compared to reference values throughout the study for both groups. Percent lactulose recovery decreased in the EEN group (admission: 22.6±8.0% day 6: 17.9 ± 2.3%) and increased in the NPO group (admission: 11.0±2.6% day 6: 22.5 ± 4.6%, P= .035). Fecal α(1)‐PI was above reference values in both groups and declined progressively. No significant differences occurred for %R, L/R ratios, or α(1)‐PI between groups. Thirteen NPO dogs and all EEN dogs survived (P= .48). The EEN group showed earlier clinical improvement and significant weight gain. The significantly decreased %L in the EEN versus NPO group might reflect improved gut barrier function, which could limit bacterial or endotoxin translocation.


title: TRATAMIENTO Y EVOLUCIÓN DEL SÍNDROME DE TORMENTA DE CITOQUINAS ASOCIADOS A INFECCIÓN POR SARS-CoV-2 EN PACIENTES OCTOGENARIOS

text: RESUMEN INTRODUCCIÓN: el síndrome de tormenta de citoquinas (STC) es una complicación muy grave de los pacientes con infección por SARS-CoV-2. El tratamiento y la evolución en octogenarios no están bien definidos. Nuestro objetivo es describir sus características clínicas, los tratamientos empleados y su evolución clínica. PACIENTES Y MÉTODO: estudio retrospectivo observacional de pacientes consecutivos ingresados con infección por SARS-CoV-2 confirmada, con neumonía por estudio radiológico o tomografía de tórax, que cumplían criterios de STC y que recibieron tratamiento. Clasificamos a los pacientes en los que recibieron sólo pulsos de glucocorticoides (GC), o pulsos de GC y tocilizumab. Determinamos niveles séricos de ferritina, PCR y dímeros-D. La variable final fue la supervivencia. RESULTADOS: 21 pacientes con una edad de 83 años (80-88 años). La ferritina media fue de 1056 microg/L (317-3553), la PCR de 115,8mg/dL (22-306) y los dímeros-D de 2,9mg/L (0,45-17,5). Todos los pacientes recibieron pulsos de GC y en dos casos simultáneamente tocilizumab. El tiempo medio de seguimiento fue de 13,7 días (8-21). La mortalidad global fue del 38,1% (8/21pacientes). Los 2 pacientes que recibieron tocilizumab fallecieron. Los fallecidos presentaron niveles significativamente más elevados de ferritina (1254 vs 925microg/L; p = 0,045) y PCR (197,6 vs 76mg/dL; p = 0,007). Al final del seguimiento se observó una disminución en los parámetros bioquímicos con ferritina de 727microg/L, PCR de 27mg/dl y DD de 1,18mg/L. En 13/21 pacientes (61,9%) el STC se controló sin necesidad de añadir otros tratamientos. CONCLUSIONES: la mortalidad del STC por SARS-CoV-2 es alta a pesar del tratamiento. Una mayor respuesta inflamatoria se asoció con una mayor mortalidad. Aunque parece que el uso precoz de pulsos de GC puede controlarlo, pudiendo disminuir la necesidad de uso de otros tratamientos como tocilizumab, con el diseño del estudio y sus limitaciones, no se puede establecer esta conclusión. ABSTRACT INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defined. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: retrospective observational study of consecutive patients admitted with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whIth STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in two cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1254 vs. 925microg/L; p=0.045) and CRP (197.6 vs. 76mg / dL; p = 0.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg / L, CRP of 27mg/dl and DD of 1.18mg / L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished.


docid: xawxmttw

title: Modelling the Economic Impact and Ripple Effects of Disease Outbreaks

text: The Coronavirus Disease 2019 (COVID-19) outbreak has had alarming effects on human lives and the economies of affected countries. With the world’s manufacturing hubs experiencing a period of extended factory closures, the economic impact transcends territorial borders via global supply chains. This paper provides a roadmap on how to evaluate the vulnerability that cascades through the supply chain due to a disease outbreak at the firm level, national level, and global scale. The final extent of losses is not yet known, but the development of economic models combined with epidemiological models and network analysis techniques can yield more realistic estimates to select appropriate strategies in a timely manner.


title: Impact of COVID-19 on Indian Sugar Industry

text: The Indian sugar industry, a significant player in the national economy, has faced many challenges in the course of its journey. The threat posed by the growing pandemic novel corona virus (COVID-19), has been the most recent one and it is impacting sugar industry stakeholders and its integrated industries, not only in India, but all over the world. The entire value chain of the Indian sugar industry, viz., sugarcane, sugar, molasses, ethanol and their subsequent marketing and export, has been adversely affected from the spillover impacts. The major impacts of COVID-19 on Indian sugar industry are discussed.


title: Identifying Meteorological Drivers for the Seasonal Variations of Influenza Infections in a Subtropical City — Hong Kong

text: Compared with temperate areas, the understanding of seasonal variations of influenza infections is lacking in subtropical and tropical regions. Insufficient information about viral activity increases the difficulty of forecasting the disease burden and thus hampers official preparation efforts. Here we identified potential meteorological factors that drove the seasonal variations in influenza infections in a subtropical city, Hong Kong. We fitted the meteorological data and influenza mortality data from 2002 to 2009 in a Susceptible-Infected-Recovered model. From the results, air temperature was a common significant driver of seasonal patterns and cold temperature was associated with an increase in transmission intensity for most of the influenza epidemics. Except 2004, the fitted models with significant meteorological factors could account for more than 10% of the variance in additional to the null model. Rainfall was also found to be a significant driver of seasonal influenza, although results were less robust. The identified meteorological indicators could alert officials to take appropriate control measures for influenza epidemics, such as enhancing vaccination activities before cold seasons. Further studies are required to fully justify the associations.


title: Detection of SARS-CoV-2 Among Residents and Staff Members of an Independent and Assisted Living Community for Older Adults — Seattle, Washington, 2020

text: In the Seattle, Washington metropolitan area, where the first case of novel coronavirus 2019 disease (COVID-19) in the United States was reported (1), a community-level outbreak is ongoing with evidence of rapid spread and high morbidity and mortality among older adults in long-term care skilled nursing facilities (SNFs) (2,3). However, COVID-19 morbidity among residents of senior independent and assisted living communities, in which residents do not live as closely together as do residents in SNFs and do not require skilled nursing services, has not been described. During March 5-9, 2020, two residents of a senior independent and assisted living community in Seattle (facility 1) were hospitalized with confirmed COVID-19 infection; on March 6, social distancing and other preventive measures were implemented in the community. UW Medicine (the health system linked to the University of Washington), Public Health - Seattle & King County, and CDC conducted an investigation at the facility. On March 10, all residents and staff members at facility 1 were tested for SARS-CoV-2, the virus that causes COVID-19, and asked to complete a questionnaire about their symptoms; all residents were tested again 7 days later. Among 142 residents and staff members tested during the initial phase, three of 80 residents (3.8%) and two of 62 staff members (3.2%) had positive test results. The three residents had no symptoms at the time of testing, although one reported an earlier cough that had resolved. A fourth resident, who had negative test results in the initial phase, had positive test results 7 days later. This resident was asymptomatic on both days. Possible explanations for so few cases of COVID-19 in this residential community compared with those in several Seattle SNFs with high morbidity and mortality include more social distancing among residents and less contact with health care providers. In addition, early implementation of stringent isolation and protective measures after identification of two COVID-19 cases might have been effective in minimizing spread of the virus in this type of setting. When investigating a potential outbreak of COVID-19 in senior independent and assisted living communities, symptom screening is unlikely to be sufficient to identify all persons infected with SARS-CoV-2. Adherence to CDC guidance to prevent COVID-19 transmission in senior independent and assisted living communities (4) could be instrumental in preventing a facility outbreak.


Acral purpuric lesions associated with coagulation disorders during the COVID‐19 pandemic


title: Epidemiology, Outcome and Risk Factors Analysis of Viral Infections in Children and Adolescents Undergoing Hematopoietic Cell Transplantation: Antiviral Drugs Do Not Prevent Epstein–Barr Virus Reactivation

text: OBJECTIVE: The analysis of epidemiology, risk factors and outcome of viral infections in children and adolescents after hematopoietic cell transplantation (HCT). METHODS: In this multicenter nationwide study a total of 971 HCT procedures (741 allo-HCT; 230 auto-HCT) over a period of 6 years were analyzed. RESULTS: During this period 801 episodes of viral infections were diagnosed in 442 patients. The incidence of viral infections was 57.9% in allo-HCT and 4.8% in auto-HCT patients. The most frequent infections after allo-HCT were caused by cytomegalovirus (CMV), polyoma BK virus (BKV) and Epstein–Barr virus (EBV). The majority of infections occurred within the first 4 months after allo-HCT and over 80% required pharmacotherapy or symptomatic therapy. The median time of treatment of specific viral infection ranged from 7 (for EBV) to 24 (for CMV) days. The highest mortality was observed in case of CMV infection. The risk factors for viral infections were allo-HCT, acute leukemia, acute and chronic graft versus host disease (a/cGVHD), and matched unrelated donor (MUD)/mismatched unrelated donor (MMUD)-HCT. The risk factor for death from viral infection were CMV-IgG seropositivity in acute lymphoblastic leukemia recipient, and MUD/MMUD-HCT. The incidence of EBV infection requiring pre-emptive treatment with rituximab in allo-HCT children was 19.3%. In 30.8% cases of EBV infection, these episodes were preceded by other viral infection and treated with antivirals, which did not prevent development of EBV-DNA-emia with need of rituximab treatment in 81.5% cases. In 47.7% of these cases, GVHD was a factor enabling development of significant EBV-DNA-emia during antiviral therapy of other infection. CONCLUSION: We have shown that antiviral drugs do not prevent EBV reactivation in allo-HCT pediatric patients.


title: Design of Potential RNAi (miRNA and siRNA) Molecules for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Gene Silencing by Computational Method

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a virus that manifests itself in viral infection with fever, cough, shortness of breath, renal failure and severe acute pneumonia, which often result in a fatal outcome. MERS-CoV has been shown to spread between people who are in close contact. Transmission from infected patients to healthcare personnel has also been observed and is irredeemable with present technology. Genetic studies on MERS-CoV have shown that ORF1ab encodes replicase polyproteins and play a foremost role in viral infection. Therefore, ORF1ab replicase polyprotein may be used as a suitable target for disease control. Viral activity can be controlled by RNA interference (RNAi) technology, a leading method for post transcriptional gene silencing in a sequence-specific manner. However, there is a genetic inconsistency in different viral isolates; it is a great challenge to design potential RNAi (miRNA and siRNA) molecules which can silence the respective target genes rather than any other viral gene simultaneously. In the current study, four effective miRNA and five siRNA molecules for silencing of nine different strains of MERS-CoV were rationally designed and corroborated using computational methods, which might lead to knockdown the activity of virus. siRNA and miRNA molecules were predicted against ORF1ab gene of different strains of MERS-CoV as effective candidate using computational methods. Thus, this method may provide an insight for the chemical synthesis of antiviral RNA molecule for the treatment of MERS-CoV, at genomic level.


docid: pbgoakqz

title: Seasonal and residential clustering at disease onset of anti-MDA5-associated interstitial lung disease

text: OBJECTIVES: To investigate whether the onset of polymyositis (PM)/dermatomyositis (DM)-associated interstitial lung disease (ILD) is influenced by season and residence in the context of myositis-specific autoantibodies. METHODS: For patients with PM/DM-associated ILD enrolled in a multicentre cohort, 365 and 481 patients were eligible for seasonal and geographical analysis, respectively, based on the availability of reliable clinical information. The patients were divided into three groups: (1) anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive patients, (2) anti-aminoacyl tRNA synthetase (anti-ARS) antibody-positive patients and (3) patients negative for those antibodies. Seasonality was assessed by the Rayleigh test. Distance from residence to the nearest waterfront was measured on Google Map and was compared between groups by the exact Wilcoxon rank-sum test. RESULTS: In anti-MDA5-positive patients, the disease developed more frequently in October–March (p=0.03), whereas a seasonal relationship was not found in the remaining two patient groups. Residence at disease onset in anti-MDA5-positive patients was significantly closer to the waterfront, especially to freshwater, compared with that in anti-ARS-positive or anti-MDA5-/ARS-negative patients (p=0.003 and 0.006, respectively). CONCLUSIONS: Anti-MDA5-associated ILD occurred predominantly from October to March in individuals residing near freshwater, suggesting an environmental influence on the onset of this disease subset.


title: Nowhere to hide: the significant impact of coronavirus disease 2019 (COVID-19) measures on elite and semi-elite South African athletes

text: Abstract Objective To describe the perceptions of South African elite and semi-elite athletes on return to sport (RTS); maintenance of physical conditioning and other activities; sleep; nutrition; mental health; healthcare access; and knowledge of coronavirus disease 2019 (COVID-19). Design Cross-sectional study Methods A Google Forms survey was distributed to athletes from 15 sports in the final phase (last week of April 2020) of the level 5 lockdown period. Descriptive statistics were used to describe player demographic data. Chi-squared tests investigated significance (p<0.05) between observed and expected values and explored sex differences. Post-hoc tests with a Bonferroni adjustment were included where applicable. Results 67% of the 692 respondents were males. The majority (56%) expected RTS after 1-6months. Most athletes trained alone (61%; p<0.0001), daily (61%; p<0.0001) at moderate intensity (58%; p<0.0001) and for 30-60min (72%). During leisure time athletes preferred sedentary above active behaviour (p<0.0001). Sleep patterns changed significantly (79%; p<0.0001). A significant number of athletes consumed excessive amounts of carbohydrates (76%; p<0.0001; males 73%; females 80%). Many athletes felt depressed (52%), and required motivation to keep active (55%). Most had access to healthcare during lockdown (80%) and knew proceedings when suspecting COVID-19 (92%). Conclusions COVID-19 had physical, nutritional and psychological consequences that may impact on the safe RTS and general health of athletes. Lost opportunities and uncertain financial and sporting futures may have significant effects on athletes and the sports industry. Government and sporting federations must support athletes and develop and implement guidelines to reduce the risk in a COVID-19 environment.


“Todo parece cambiar pero en el fondo no cambia nada”: La pandemia del Covid‐19 en ciudades medias latinoamericanas


title: Viral pneumonia in patients with hematologic malignancy or hematopoietic stem cell transplantion

text: Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging.


Confronting the Pandemic Superthreat of Climate Change and Urbanization


title: Evaluation of rapid diagnosis of novel coronavirus disease (COVID-19) using loop-mediated isothermal amplification

text: With the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for more rapid and simple detection technologies at the forefront of medical care worldwide. In this study, we evaluated the effectiveness of the Loopamp® 2019-SARSCoV-2 Detection Reagent Kit, which uses loop-mediated isothermal amplification (LAMP) technology. In this protocol, cDNA is synthesized from SARS-CoV-2 RNA using reverse transcriptase, followed by DNA amplification under isothermal conditions in one step. The RT-LAMP test kit amplified the targeted RNA of a SARS-CoV-2 isolate with a detection limit of 1.0 × 101 copies/μL, which was comparable to the detection sensitivity of quantitative reverse transcription PCR (RT-qPCR). Comparison with the results of RT-qPCR for 76 nasopharyngeal swab samples from patients with suspected COVID-19 showed a sensitivity of 100% and a specificity of 97.6%. In the 24 RNA specimens derived from febrile Japanese patients with or without influenza A, no amplification was observed using RT-LAMP. RT-LAMP could be a simple and easy-to-use diagnostic tool for the detection of SARS-CoV-2.


title: Efficacy of injectable toltrazuril-iron combination product and oral toltrazuril against early experimental infection of suckling piglets with Cystoisospora suis

text: BACKGROUND: Toltrazuril is frequently administered for the metaphylactic control of piglet cystoisosporosis. In a previous study, the efficacy of parenteral toltrazuril (45 mg/piglet, Group Forceris®) applied on the 2nd day of life (dol), and of oral toltrazuril (20 mg/kg of body weight, Group Baycox®) applied on the 4th dol was evaluated in an experimental model with Cystoisospora suis infection on the 3rd dol (late infection, LI). In a follow-up study, efficacy and safety were evaluated against infections with C. suis on the 1st dol (early infection, EI). Parameters included oocyst excretion and faecal consistency, body weight development, bacteriological examinations and animal health. RESULTS: All control piglets (n = 12) shed oocysts and had diarrhoea, while parasite excretion was completely suppressed in both treatment groups (n = 13 each) and diarrhoea was reduced to a single animal (Forceris® group), resulting in significant differences for these parameters between the treated groups and the controls without significant differences among the treatment groups. No treatment-related adverse events were noted. Body weight gain was reduced in the control group during the acute phase of infection, resulting in significantly lower body weight on the 15th dol. Sows and piglets shed high numbers of Escherichia coli. Clostridium perfringens type A was only detected in low amounts in pooled litter samples. In comparison to the LI study oocyst shedding was more intense in the control animals in EI, while diarrhea was more frequent in LI. In both infection models a high efficacy of toltrazuril in the control of parasitological and clinical outcomes of experimental C. suis infection could be demonstrated. Since in the LI study high numbers of Cl. perfringens type A were detected, it is hypothesized that colonization with these opportunistic pathogens has synergistic effects with C. suis and may explain variable clinical outcomes in untreated animals as well as the sporadic occurrence of diarrhea in toltrazuril-treated piglets. CONCLUSIONS: Parenteral and oral toltrazuril administered on the 2nd or 4th dol is safe and effective against experimental infections with C. suis on the 1st to 3rd dol. The clinical outcome of experimental infections seems influenced by bacterial coinfections.


title: Ferrocene Conjugates of Chloroquine and other Antimalarials: the Development of Ferroquine, a New Antimalarial

text: A convenient approach to antimalarial drug discovery is the use of the organic scaffold of a known antimalarial drug and an organometallic moiety to alter its unwanted properties and/or to optimize its initial effects. This minireview focuses mainly on the discovery of ferroquine, which has emerged from a collaborative French discovery project, and efforts to understand its mechanism of action and resistance.[Image: see text]


title: Lipid-based delivery systems and intestinal lymphatic drug transport: A mechanistic update

text: Abstract After oral administration, the majority of drug molecules are absorbed across the small intestine and enter the systemic circulation via the portal vein and the liver. For some highly lipophilic drugs (typically log P >5, lipid solubility>50 mg/g), however, association with lymph lipoproteins in the enterocyte leads to transport to the systemic circulation via the intestinal lymph. The attendant delivery benefits associated with lymphatic drug transport include a reduction in first-pass metabolism and lymphatic exposure to drug concentrations orders of magnitude higher than that attained in systemic blood. In the current review we briefly describe the mechanisms by which drug molecules access the lymph and the formulation strategies that may be utilised to enhance lymphatic drug transport. Specific focus is directed toward recent advances in understanding regarding the impact of lipid source (both endogenous and exogenous) and intracellular lipid trafficking pathways on lymphatic drug transport and enterocyte-based first-pass metabolism.


title: System dynamics evaluation of household water use behavior and associated greenhouse gas emissions and environmental costs: A case study of Taipei city

text: Abstract Taiwan is an island surrounded by sea and only 19 % of its freshwater usage is for domestic applications. A system dynamic model was developed to investigate interactions between household water use behaviors (toilet flushing, clothes washing, bathing/showering, and cleaning) and associated greenhouse gas emissions and environmental costs. Six hundred and fifty face-to-face interviews were conducted in 12 districts of Taipei. The results showed that the respondents’ individual attributes were not significantly related to water use behaviors. The highest volume of water was used for cleaning (27.7 %), followed by clothes washing (26.2 %), bathing/showering (26.1 %), and toilet flushing (20.0 %). Five water management scenarios with 5 %–20 % reductions in water volume from different water use behaviors were simulated. The maximum reduction in water use (6.27 t) was found in the fifth scenario (20 % reduction), which reflected the priority the respondents gave to save water if its price increased. 27.2 % of respondents had water saving appliances; 20.5 % and 16.4 % of the appliances were toilets and shower heads, respectively. The environmental cost of GHG emissions associated with water use behavior was US$0.001/t, causing an 8% increase in water price. A better understanding of household water use behaviors is needed to develop bottom-up strategies or measures for sustainable water management. Water saving measures or strategies would lead to targets being met in a short time.


title: A Trans-Specific Polymorphism in ZC3HAV1 Is Maintained by Long-Standing Balancing Selection and May Confer Susceptibility to Multiple Sclerosis

text: The human ZC3HAV1 gene encodes an antiviral protein. The longest splicing isoform of ZC3HAV1 contains a C-terminal PARP-like domain, which has evolved under positive selection in primates. We analyzed the evolutionary history of this same domain in humans and in Pan troglodytes. We identified two variants that segregate in both humans and chimpanzees; one of them (rs3735007) does not occur at a hypermutable site and accounts for a nonsynonymous substitution (Thr851Ile). The probability that the two trans-specific polymorphisms have occurred independently in the two lineages was estimated to be low (P = 0.0054), suggesting that at least one of them has arisen before speciation and has been maintained by selection. Population genetic analyses in humans indicated that the region surrounding the shared variants displays strong evidences of long-standing balancing selection. Selection signatures were also observed in a chimpanzee population sample. Inspection of 1000 Genomes data confirmed these findings but indicated that search for selection signatures using low-coverage whole-genome data may need masking of repetitive sequences. A case–control study of more than 1,000 individuals from mainland Italy indicated that the Thr851Ile SNP is significantly associated with susceptibility to multiple sclerosis (MS) (odds ratio [OR] = 1.47, 95% confidence intervals [CI]: 1.08–1.99, P = 0.011). This finding was confirmed in a larger sample of 4,416 Sardinians cases/controls (OR = 1.18, 95% CI: 1.037–1.344, P = 0.011), but not in a population from Belgium. We provide one of the first instances of human/chimpanzee trans-specific coding variant located outside the major histocompatibility complex region. The selective pressure is likely to be virus driven; in modern populations, this variant associates with susceptibility to MS, possibly via the interaction with environmental factors.


title: Potential role of statins in COVID-19

text: Abstract Patients with COVID-19 infection have an increased risk of cardiovascular complications and thrombotic events. Statins are known for their pleiotropic anti-inflammatory, antithrombotic and immunomodulatory effects. They may have a potential role as adjunctive therapy to mitigate the effects of endothelial dysfunction and dysregulated inflammation in patients with COVID-19 infection.


title: Evolutionary biology of human hepatitis viruses

text: Hepatitis viruses are major threats to human health. During the last decade, highly diverse viruses related to human hepatitis viruses were found in animals other than primates. Herein, we describe both surprising conservation and striking differences of the unique biological properties and infection patterns of human hepatitis viruses and their animal homologues, including transmission routes, liver tropism, oncogenesis, chronicity, pathogenesis and envelopment. We discuss the potential for translation of newly discovered hepatitis viruses into preclinical animal models for drug testing, studies on pathogenesis and vaccine development. Finally, we re-evaluate the evolutionary origins of human hepatitis viruses and discuss the past and present zoonotic potential of their animal homologues.


title: In vitro anti-reovirus activity of kuraridin isolated from Sophora flavescens against viral replication and hemagglutination

text: Abstract In this study, we evaluated the anti-reovirus activity of kuraridin isolated from the roots of Sophora flavescens. In particular, we focused on whether this property is attributable to direct inhibition of reovirus attachment and/or inhibition of viral replication with the aid of time-of-addition (pre-treatment, simultaneous treatment, and post-treatment) experiments. No significant antiviral activity of kuraridin was detected in the pre-treatment assay. In the simultaneous assay, the 50% effective inhibitory concentrations (EC50) of kuraridin were 15.3–176.9 μM against human type 1–3 reoviruses (HRV1–3) and Korean porcine reovirus (PRV). Kuraridin completely blocked binding of viral sigma 1 protein to sialic acids at concentrations lower than 82.5 μM in the hemagglutination inhibition assay. Moreover, kuraridin inhibited HRV1–3 and PRV viral replication with EC50 values of 14.0–62.0 μM. Quantitative real-time PCR analysis disclosed strong suppression of reovirus RNA synthesis at the late stage (18 h) of virus replication by kuraridin. The viral yields of kuraridin-treated cells were significantly reduced at 24 h post-infection, compared with DMSO-treated cells. Our results collectively suggest that kuraridin inhibits virus adsorption and replication by inhibiting hemagglutination, viral RNA and protein synthesis and virus shedding, supporting its utility as a viable candidate antiviral drug against reoviruses.


title: Vector-based genetically modified vaccines: Exploiting Jenner’s legacy

text: Abstract The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of ’smarter’ vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner’s vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors that may help us control other major scourges of mankind.


Essentials of donning, doffing, and changes in endoscopy practice to reduce the risk of spreading COVID-19 during endoscopy


Prevalence of Anxiety and Associated Factors for Chinese Adolescents during the COVID‐19 Outbreak


title: Comparing national infectious disease surveillance systems: China and the Netherlands

text: BACKGROUND: Risk assessment and early warning (RAEW) are essential components of any infectious disease surveillance system. In light of the International Health Regulations (IHR)(2005), this study compares the organisation of RAEW in China and the Netherlands. The respective approaches towards surveillance of arboviral disease and unexplained pneumonia were analysed to gain a better understanding of the RAEW mode of operation. This study may be used to explore options for further strengthening of global collaboration and timely detection and surveillance of infectious disease outbreaks. METHODS: A qualitative study design was used, combining data retrieved from the literature and from semi-structured interviews with Chinese (5 national-level and 6 provincial-level) and Dutch (5 national-level) experts. RESULTS: The results show that some differences exist such as in the use of automated electronic components of the early warning system in China (‘CIDARS’), compared to a more limited automated component in the Netherlands (‘barometer’). Moreover, RAEW units in the Netherlands focus exclusively on infectious diseases, while China has a broader ‘all hazard’ approach (including for example chemical incidents). In the Netherlands, veterinary specialists take part at the RAEW meetings, to enable a structured exchange/assessment of zoonotic signals. CONCLUSION: Despite these differences, the main conclusion is that for the two infections studied, the early warning system in China and the Netherlands are remarkably similar considering their large differences in infectious disease history, population size and geographical setting. Our main recommendations are continued emphasis on international corporation that requires insight into national infectious disease surveillance systems, the usage of a One Health approach in infectious disease surveillance, and further exploration/strengthening of a combined syndromic and laboratory surveillance system.


title: A mathematical model reveals the influence of population heterogeneity on herd immunity to SARS-CoV-2

text: Despite various levels of preventive measures, in 2020 many countries have suffered severely from the coronavirus 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We show that population heterogeneity can significantly impact disease-induced immunity as the proportion infected in groups with the highest contact rates is greater than in groups with low contact rates. We estimate that if R(0) = 2.5 in an age-structured community with mixing rates fitted to social activity then the disease-induced herd immunity level can be around 43%, which is substantially less than the classical herd immunity level of 60% obtained through homogeneous immunization of the population. Our estimates should be interpreted as an illustration of how population heterogeneity affects herd immunity, rather than an exact value or even a best estimate.


title: A Predictive Model for the Evolution of COVID-19

text: We predict the evolution of the COVID-19 pandemic in several countries using a logistic model. The model uses a regression analysis based on the least-squares fitting. In particular, the growth rate of the infection has been fitted as an exponential decay, as compared to a linear decay, reported previously in logistic models. The model has been validated with the data of China and South Korea, where the pandemic is nearing to its end. The data of Italy, Germany, Spain, and Sweden show that the peak of the infection has been reached, i.e. a time when the new infections will start to decrease as compared to the previous day. The model predicts the approximate number of total infections at the end of the outbreak. The possible peak date and the total number of infections for different countries are predicted using the data available. The total number of infections in the USA is estimated to be around 4 million. The model prediction of Brazil shows that the peak will reach on 5 July 2020 and total infections will be 3.2 million. The reported data of India show a large initial scatter in the growth rate. The total number of infections in India is estimated to be around 2.4 million by the model and the predicted peak date is 3 August 2020. The predictions of India are discussed in the context of restricted movement of population, i.e. lock-down imposed by the government.


title: Anti-Influenza A Virus Activity of Rhamnan Sulfate from Green Algae Monostroma nitidum in Mice with Normal and Compromised Immunity

text: Influenza viruses cause a significant public health burden each year despite the availability of anti-influenza drugs and vaccines. Therefore, new anti-influenza virus agents are needed. Rhamnan sulfate (RS) is a sulfated polysaccharide derived from the green alga Monostroma nitidum. Here, we aimed to demonstrate the antiviral activity of RS, especially against influenza A virus (IFV) infection, in vitro and in vivo. RS showed inhibitory effects on viral proliferation of enveloped viruses in vitro. Evaluation of the anti-IFV activity of RS in vitro showed that it inhibited both virus adsorption and entry steps. The oral administration of RS in IFV-infected immunocompetent and immunocompromised mice suppressed viral proliferation in both mouse types. The oral administration of RS also had stimulatory effects on neutralizing antibody production. Fluorescent analysis showed that RS colocalized with M cells in Peyer’s patches, suggesting that RS bound to the M cells and may be incorporated into the Peyer’s patches, which are essential to intestinal immunity. In summary, RS inhibits influenza virus infection and promotes antibody production, suggesting that RS is a potential candidate for the treatment of influenza virus infections.


title: The Urban-Rural Disparity in the Status and Risk Factors of Health Literacy: A Cross-Sectional Survey in Central China

text: Health literacy is the ability of individuals to access, process, and understand health information to make decisions regarding treatment and their health on the whole; it is critical to maintain and improve public health. However, the health literacy of urban and rural populations in China has been little known. Thus, this study aims to assess the status of health literacy and explore the differences of its possible determinants (e.g., socio-economic factors) among urban and rural populations in Henan, China. A cross-sectional study, 78,646 participants were recruited from a populous province in central China with a multi-stage random sampling design. The Chinese Resident Health Literacy Scale was adopted to measure the health literacy of the respondents. In the participants, the level of health literacy (10.21%) in central China was significantly lower than the national average, and a big gap was identified between urban and rural populations (16.92% vs. 8.09%). A noticeable difference was reported in different aspects and health issues of health literacy between urban and rural populations. The health literacy level was lower in those with lower levels of education, and a significant difference was identified in the level of health literacy among people of different ages and occupations in both urban and rural areas. Note that in rural areas, as long as residents educated, they all had higher odds to exhibit basic health literacy than those uneducated; in rural areas, compared with those aged 15 to 24 years, residents aged 45 to 54 years (OR = 0.846,95% CI (0.730, 0.981)), 55 to 64 years (OR = 0.716,95% CI (0.614, 0.836)) and above 65 years (OR = 0.679, 95% CI (0.567, 0.812)) were 84.6%, 71.6%, and 67.9%, respectively, less likely to exhibit basic health literacy. Considering the lower health literacy among rural residents compared with their urban counterparts, a reorientation of the health policy-making for Chinese rural areas is recommended. This study suggests that urban–rural disparity about health literacy risk factors should be considered when implementing health literacy promotion intervention.


title: Trade credit research before and after the global financial crisis of 2008 – A bibliometric overview

text: Abstract This study presents an overview of the state-of-the-art in trade credit research by examining 1191 publications between 1955 and 2019. Applying bibliometric and econometric tools, this study presents a comparative analysis of the extant research across the three sub-domains of banking and finance, production and operations, and accounting. Findings suggest that the financial emergency in the global market had resulted in a watershed moment in trade credit research. About 69 % of the literature was found to have emerged after the global economic crisis of 2008. A network analysis grouped the trade credit articles into four major and four minor clusters. The banking and financing cluster exhibited the highest growth followed by the production and operation cluster while the perspectives of accounting are yet to gain traction. Conversely, reputation of the publishing hub, empirical studies, and the production and operational dimensions of the research positively and significantly influence citations. Alongside thorough introspection, the study also provides new areas to direct the course of future research.


title: On Tuberculosis and COVID-19 co-infection

text: COVID-19 may boost tuberculosis given infection and mortality, further studies are needed


COVID-19 pandemic and cardiovascular complications: what have we learned so far?


title: Risk factors for severe bronchiolitis caused by respiratory virus infections among Mexican children in an emergency department

text: Severe bronchiolitis is the most common reason for hospitalization among children younger than 2 years. This study analyzed the prevalence of community-acquired respiratory virus infection and the risk factors for hospitalization of Mexican children with severe bronchiolitis treated in an Emergency department. This retrospective study included 134 children 2 years or younger with severe viral bronchiolitis, and 134 healthy age-matched controls. The study period was September 2012 to January 2015. We determined the viral etiology and coinfections with multiple viruses and compared the risk factors detected in children with severe viral bronchiolitis with those in the control group. A total of 153 respiratory viruses in these 134 patients, single or mixed infections, were identified: respiratory syncytial virus (RSV) type A or B was the most frequently detected (23.6% and 17.6%, respectively), followed by rhinovirus (RV; 16.3%) and parainfluenza virus (PIV) type 3 (12.4%). Coinfections of 2 respiratory viruses were found in 14.2% of cases; all cases had either RSV type A or B with another virus, the most common being parainfluenza virus or rhinovirus. Exposure to cigarette smoking was independently associated with hospitalization for severe bronchiolitis (OR, 3.5; 95% CI, 1.99–6.18; P = .0001), and having completed the vaccination schedule for their age was a protective factor against adverse outcome (OR, 0.55; 95% CI, 0.35–0.87; P = .010). RSV is a common infection among young children with severe bronchiolitis; thus, developing a vaccine against RSV is essential. Campaigns to reinforce the importance of avoiding childhood exposure to cigarette smoke are also needed.


Histological–ultrasonographical correlation of pulmonary involvement in severe COVID-19


title: Containment of future waves of COVID-19: simulating the impact of different policies and testing capacities for contact tracing, testing, and isolation

text: We used multi-agent simulations to estimate the testing capacity required to find and isolate a number of infections sufficient to break the chain of transmission of SARS-CoV-2. Depending on the mitigation policies in place, a daily capacity between 0.7 to 3.6 tests per thousand was required to contain the disease. However, if contact tracing and testing efficacy dropped below 60% (e.g. due to false negatives or reduced tracing capability), the number of infections kept growing exponentially, irrespective of any testing capacity. Under these conditions, the population’s geographical distribution and travel behaviour could inform sampling policies to aid a successful containment.