title: Rice dwarf phytoreovirus segment S12 transcript is tricistronic in Vitro

text: Abstract Sequence analysis revealed that rice dwarf phytoreovirus segment S12 is 1066 nucleotides long with a small out-of-phase, overlapping open reading frame (ORF) as well as a major ORF. The large ORF (positions 42 to 980) encodes 312 amino acids, while the small one (bases 313 to 591) encodes 92 amino acids with an additional in-frame AUG codon (positions 337–339) 24 nucleotides downstream from the first one. Transcripts from a full-length cDNA directed the in vitro synthesis of three polypeptides of 33 (considered to be translated from the long ORF), 8, and 7 kDa. Alteration of each of the two ATG codons on the small ORF demonstrated their involvement in the generation of the 8- and 7-kDa polypeptides. Although it is still unknown whether these proteins are expressed in vivo, the small ORF is shown to be conserved in S9s of two other members of the genus Phytoreovirus, rice gall dwarf virus and wound tumor virus, suggesting its common, important function.


title: Mouse hepatitis virus nucleocapsid protein-specific cytotoxic T lymphocytes are Ld restricted and specific for the carboxy terminus

text: Abstract Infection of mice with the JHM strain of mouse hepatitis virus (MHV) results in an acute encephalomyelitis associated with primary demyelination of the central nervous system. Efforts at understanding the components of the immune response in the development of chronic MHV-induced demyelination have implicated the antibody response and both the CD4+ and CD8+ T cell responses. In this report, we demonstrate that Balb/c (H-2°) mice immunized with the JHM (JHMV) strain of MHV develop a CD8+ cytotoxic T lymphocyte (CTL) response. One population of these virus-specific CTL recognize the nucleocapsid (N) protein. Recombinant vaccinia viruses expressing either the entire N protein or carboxy-terminal deletions were used to determine the number and location of the epitope(s) recognized. The CTLs were found to recognize a peptide contained within the carboxy-terminal 149 amino acids of the N protein. Analysis of infected cell lines expressing transfected major histocompatibility genes demonstrated that the anti-N protein CTLs were restricted exclusively to the L° molecule. These data provide the first definition of a MHV-specific CTL response directed to a viral protein and suggest that the anti-N protein CTL response is one potential mechanism used by the host to clear JHMV from the central nervous system.


title: Neurosensory dysfunction: a diagnostic marker of early COVID-19

text: Abstract Objectives To detailly described the neurosensory dysfunction, including hyposmia, hypogeusia and tinnitus, in patients with COVID-19. Methods Clinical characteristics and oropharyngeal swabs were obtained from 86 patients with COVID-19 hospitalized in Guangzhou Eighth People’s Hospital. Chronological analysis method was used to detailly clarify the neurosensory dysfunction. The cycle threshold (Ct) values were used to approximately indicate viral load. Results Forth-four (51.2%) patients had neurosensory dysfunction: hyposmia (34, 39.5%), hypogeusia (33, 38.4%), and tinnitus (3, 3.5%). Neurosensory dysfunction was significantly more common in patients under 40 years old (p = 0.001) or women (p = 0.006). Hyposmia and hypogeusia coexisted in 23 (26.7%) patients. The interval between onset of hyposmia and hypogeusia was 0.7 ± 1.46 days. The interval from onset of hyposmia and hypogeusia to typical symptoms was 0.22 ± 4.57 and 0.75 ± 6.77 days; the interval from onset of hyposmia and hypogeusia to admission was 6.06 ± 6.68 and 5.76 ± 7.68 days; and the duration of hyposmia and hypogeusia was 9.09 ± 5.74 and 7.12 ± 4.66 days, respectively. The viral load was high since symptoms onset, peaked within the first week, and then gradually declined. Conclusions The neurosensory dysfunction tends to occur in the early stage of COVID-19, and it could be used as a marker for early diagnosis of COVID-19.


title: Impact of COVID‐19 on cardiac surgical training: Our experience in the United Kingdom

text: The current evolving global pandemic caused by coronavirus disease‐2019 (COVID‐19) has dramatically impacted global health care systems, resulting in governments taking unprecedented measures to contain the spread of the infection, with adaptations by health care organizations. Research into understanding the pathophysiology behind this virus, to ascertain best medical management and treatment, has been accelerated to keep up with the rapidly evolving situation. There has been redeployment of medical and nursing staff to the frontlines and redistribution of health care resources. In addition, the cancellation of elective surgery and centralization of services to treat high‐risk surgical cases will all, undeniably, have an impact on current surgical training with possible future implications. We aim to explore the impact COVID‐19 is having on cardiac surgical training in the UK and what future implications this may have.


title: Haematological and Immunological Data of Chinese Children Infected with Coronavirus Disease 2019

text: Haematological and immunological data of children with COVID-19 infection is lacking. Between 21(st) January and 20(th) March 2020, 244 children who were confirmed to have COVID-19 infection and admitted to the Wuhan Children's Hospital, China were retrospectively reviewed. 193 children were considered as symptomatic, which was defined as having either the presence of clinical symptoms or the presence of CT thorax abnormalities. Their haematological and immunological profiles, including complete blood counts, lymphocyte subsets (T, B and NK cell counts), immunoglobulin (Ig) profiles (IgG, IgA and IgM) and cytokine profiles were analysed and compared between the symptomatic and asymptomatic groups. The median values and the interquartile ranges were calculated. Comparison was made using the Mann–Whitney U test. Children with symptomatic COVID-19 infection had significantly lower haemoglobin levels, but higher absolute lymphocyte and monocyte counts, IgG and IgA levels, as well as interleukin 6 (IL-6), IL-10, tumour necrosis factor alpha and interferon gamma levels. The obtained data will be utilized for further studies in comparing children and adults with COVID-19 infections in other parts of the world and with different severity.


title: Identification of Enterococcus faecalis in a patient with urinary-tract infection based on metagenomic next-generation sequencing: a case report

text: BACKGROUND: Urinary tract infection (UTI) caused by various pathogenic microorganisms is ubiquitous in the parts of the urinary system such as kidney, ureter, bladder, and urethra. Currently, clinical detection of UTI is mainly focused on urine culture; however, the diagnostic value of urine culture remains limited due to the time-consuming procedure and low detection rate, especially in patients who have used antibiotics. Generally, treatment for UTI relies on empirical medication rather than pathogen diagnosis, which leads to the inappropriate use of antimicrobial agents and a significant increase in resistant strains. Comparatively, metagenomic next-generation sequencing (mNGS) is capable of overcoming the disadvantages of clinical culture, and identifying pathogens for further treatment. CASE PRESENTATION: A 33-year-old male patient was admitted to hospital with a high fever and chills. None of his autoimmune disease or thyroid function related indicators were positive, and he had no risk of endocarditis. His white blood cell count, C-reactive protein, procalcitonin, interleukin 6, and neutrophil proportion were markedly elevated. He was initially diagnosed as having an infection of unknown etiology. Since empirical treatment of Sulperazon and Metronidazole did not relieve his symptoms, both the blood and urine specimens were examined using traditional culture, serological testing, and mNGS assay. Traditional culture and serological testing produced negative results, while the mNGS assay revealed the presence of a potential pathogen, Enterococcus faecalis, in the urine specimen, which was further confirmed by both Sanger sequencing and qPCR analysis. A CT scan of the patient’s whole abdomen showed stones in the right kidney. Once targeted antibiotic therapy was administered, the patient recovered quickly. CONCLUSIONS: Our case illustrated that mNGS, as a novel culture-independent approach, demonstrated the capability of rapid, sensitive, and accurate pathogen identification. Furthermore, this technology provides strong support for guiding clinicians to determine appropriate treatment.


title: Accessible COVID‐19 tracker enables a way for visually impaired to stay up to date

text: Tyler Littlefield, a software developer who is blind with only light perception, has created a fully accessible tracker of COVID‐19 statistics as a resource for those who are blind or visually impaired. The majority of information regarding ongoing statistics and updates about the spread of COVID‐19 in the United States is conducted graphically, which can be a problem for the blind or visually impaired. The tracker, called CVStats, converts statistics about COVID‐19 from a graphical to a text format, making it easier for those who work exclusively with screen readers to access the information.


title: Catalytic activity regulation through post-translational modification: the expanding universe of protein diversity

text: Protein composition is restricted by the genetic code to a relatively small number of natural amino acids. Similarly, the known three-dimensional structures adopt a limited number of protein folds. However, proteins exert a large variety of functions and show a remarkable ability for regulation and immediate response to intracellular and extracellular stimuli. To some degree, the wide variability of protein function can be attributed to the post-translational modifications. Post-translational modifications have been observed in all kingdoms of life and give to proteins a significant degree of chemical and consequently functional and structural diversity. Their importance is partly reflected in the large number of genes dedicated to their regulation. So far, hundreds of post-translational modifications have been observed while it is believed that many more are to be discovered along with the technological advances in sequencing, proteomics, mass spectrometry and structural biology. Indeed, the number of studies which report novel post translational modifications is getting larger supporting the notion that their space is still largely unexplored. In this review we explore the impact of post-translational modifications on protein structure and function with emphasis on catalytic activity regulation. We present examples of proteins and protein families whose catalytic activity is substantially affected by the presence of post translational modifications and we describe the molecular basis which underlies the regulation of the protein function through these modifications. When available, we also summarize the current state of knowledge on the mechanisms which introduce these modifications to protein sites.


title: Microbiology in Clinical Pathology

text: Abstract Medical microbiology involves the identification of microorganisms for the diagnosis of infectious diseases and the assessment of likely response to specific therapeutic interventions. Major categories of organisms include bacteria, mycobacteria, fungi, viruses, and parasites. Microbiological methods combined with clinical symptoms, additional laboratory tests, and imaging techniques are used in combination to distinguish a true disease-associated infection from colonization with normal flora or other conditions, such as malignancies, inflammatory disorders, or autoimmune disorders, all of which have unique therapies and prognoses for the patient. Laboratories combine the use of traditional microscopy and culture methods, with a rapidly evolving set of molecular and proteomic techniques. Given the increase in immunocompromised patients due to an increase in transplantations, the human immunodeficiency virus epidemic, and the use of immunosuppressive agents to treat autoimmune disorders, diagnosis of microbial infections continues to be essential for many patients.


title: Reversible restriction of vesicular stomatitis virus in permissive cells treated with inhibitors of prostaglandin biosynthesis

text: Abstract Indomethacin, a potent nonsteroidal inhibitor of prostaglandin synthetase (cyclooxygenase) reduced yields of infectious vesicular stomatitis virus in HEp-2 cells more than 99% if added to cultures at levels of 10−3 M either before or after infection. Other permissive cell lines differed according to the treatment period and drug level required for restricting productive infections. The inhibitory effect of indomethacin was progressively reduced if infection of cells was delayed for increasing times after drug removal. Strong inhibition of viral replication also occurred in cells treated with the cyclooxygenase antagonists naproxen, phenylbutazone, and oxyphenylbutazone whereas phenacetin, which does not block cyclooxygenase function, was inactive. Enhanced viral replication occurred in indomethacin-treated HEp-2 cultures when these cells were subsequently exposed to such substances as prostaglandin El, cyclic AMP, or insulin. Conversely, indomethacin-treated cells remained restrictive for VSV if they were subsequently exposed to metabolic inhibitors of functional DNA (actinomycin D or mitomycin C), messenger RNA synthesis (α-amanitin), or protein synthesis (cycloheximide) at concentrations that normally do not compromise viral replication. Pretreatment of HEp-2 cells with mitomycin C markedly shifted the dose response for indomethacin-mediated inhibition of VSV from a 90% inhibitory dose of about 10−4 M to one of 10−9 M or lower. These findings suggest that preexisting host factors essential for replication of VSV, although rendered nonfunctional by the drug indomethacin, can be replenished unless their synthesis is blocked by various classes of metabolic inhibitors.


title: Progress in tuberculosis control and the evolving public-health system in China

text: Summary China has the world's second largest tuberculosis epidemic, but progress in tuberculosis control was slow during the 1990s. Detection of tuberculosis had stagnated at around 30% of the estimated total of new cases, and multidrug-resistant tuberculosis was a major problem. These signs of inadequate tuberculosis control can be linked to a malfunctioning health system. The spread of severe acute respiratory syndrome (SARS) in 2003, brought to light substantial weaknesses in the country's public-health system. After the SARS epidemic was brought under control, the government increased its commitment and leadership to tackle public-health problems and, among other efforts, increased public-health funding, revised laws that concerned the control of infectious diseases, implemented the world's largest internet-based disease reporting system, and started a programme to rebuild local public-health facilities. These measures contributed to acceleration in efforts to control tuberculosis. By 2005, the detection of cases of tuberculosis had increased to 80% of the estimated total new cases, permitting China to achieve the 2005 global tuberculosis control targets. At the same time, specific efforts to improve tuberculosis control also contributed to strengthening of the public-health system. We examine how the strengthening of a disease control programme and the public-health system worked together to achieve a desired health outcome.


title: Perceived Discrimination and Mental Distress Amid the COVID-19 Pandemic: Evidence From the Understanding America Study

text: Introduction This study examines coronavirus disease 2019 (COVID-19) associated discrimination regardless of infection status. It evaluates the contribution of various risk factors (e.g., race/ethnicity, wearing a face mask) and the relationship with mental distress among U.S. adults in March and April 2020, when the pandemic escalated across the country. Methods Participants consisted of a probability-based, nationally representative sample of U.S. residents aged ≥18 years who completed COVID-19-related surveys online in March and April (n=3,665). Multivariable logistic regression was used to predict the probability of a person perceiving COVID-19 associated discrimination. Linear regression was used to analyze the association between discrimination and mental distress. Analyses were conducted in May 2020. Results Perception of COVID-19 associated discrimination increased from March (4%) to April (10%). Non-Hispanic blacks (absolute risk from 0.09 to 0.15 across months) and Asians (absolute risk from 0.11 to 0.17) were more likely to perceive discrimination than other racial/ethnic groups (absolute risk from 0.03 to 0.11). Individuals who wore face masks (absolute risk from 0.11 to 0.14) also perceived more discrimination compared with those who did not (absolute risk from 0.04 to 0.11). Perceiving discrimination was subsequently associated with increased mental distress (from 0.77 to 1.01 points on the 4-item Patient Health Questionnaire score). Conclusions Perception of COVID-19 associated discrimination was relatively low but increased with time. Perceived discrimination was associated with race/ethnicity and wearing face masks, and may contribute to greater mental distress during early stages of the pandemic. The long-term implications of this novel form of discrimination should be monitored.


title: The role of viral co-infections in the severity of acute respiratory infections among children infected with respiratory syncytial virus (RSV): A systematic review and meta-analysis

text: BACKGROUND: Respiratory syncytial virus (RSV) is the predominant viral cause of childhood pneumonia. Little is known about the role of viral-coinfections in the clinical severity in children infected with RSV. METHODS: We conducted a systematic literature review of publications comparing the clinical severity between RSV mono-infection and RSV co-infection with other viruses in children under five years (<5y). Clinical severity was measured using the following six clinical outcomes: hospitalisation, length of hospital stay, use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarised the findings by clinical outcome and conducted random-effect meta-analyses, where applicable, to quantitatively synthesize the association between RSV mono-infection/RSV co-infection and the clinical severity. RESULTS: Overall, no differences in the clinical severity were found between RSV mono-infection and RSV co-infection with any viruses, except for the RSV-human metapneumovirus (hMPV) co-infection. RSV-hMPV coinfection was found to be associated with a higher risk of ICU admission (odds ratio (OR) = 7.2, 95% confidence interval (CI) = 2.1-25.1; OR after removal of the most influential study was 3.7, 95% CI = 1.1-12.3). We also observed a trend from three studies that RSV-hMPV coinfections were likely to be associated with longer hospital stay. CONCLUSION: Our findings suggest that RSV-hMPV coinfections might be associated with increased risk for ICU admission in children <5y compared with RSV mono-infection but such association does not imply causation. Our findings do not support the association between RSV coinfections with other viruses and clinical severity but further large-scale investigations are needed to confirm the findings. PROTOCOL REGISTRATION: PROSPERO CRD42019154761.


title: Recomendaciones de consenso respecto al soporte respiratorio no invasivo en el paciente adulto con insuficiencia respiratoria aguda secundaria a infección por SARS-CoV-2

text: Resumen La enfermedad por coronavirus 2019 (COVID-19) es una infección del tracto respiratorio causada por un nuevo coronavirus emergente que se reconoció por primera vez en Wuhan, China, en diciembre de 2019. Actualmente la Organización Mundial de la Salud (OMS) ha definido la infección como pandemia y existe una situación de emergencia sanitaria y social para el manejo de esta nueva infección. Mientras que la mayoría de las personas con COVID-19 desarrollan solo una enfermedad leve o no complicada, aproximadamente el 14% desarrollan una enfermedad grave que requiere hospitalización y oxígeno, y el 5% pueden requerir ingreso en una Unidad de Cuidados Intensivos. En casos severos, COVID-19 puede complicarse por el síndrome de dificultad respiratoria aguda (SDRA), sepsis y shock séptico y fracaso multiorgánico. Este documento de consenso se ha preparado sobre directrices basadas en evidencia desarrolladas por un panel multidisciplinario de profesionales médicos de cuatro sociedades científicas españolas (Sociedad Española de Medicina Intensiva y Unidades Coronarias [SEMICYUC], Sociedad Española de Neumología y Cirugía Torácica [SEPAR], Sociedad Española de Urgencias y Emergencias [SEMES], Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor [SEDAR]) con experiencia en el manejo clínico de pacientes con COVID-19 y otras infecciones virales, incluido el SARS, así como en sepsis y SDRA. El documento proporciona recomendaciones clínicas para el soporte respiratorio no invasivo (ventilación no invasiva, oxigenoterapia de alto flujo con cánula nasal) en cualquier paciente con presentación sospechada o confirmada de COVID-19 con insuficiencia respiratoria aguda. Esta guía de consenso debe servir como base para una atención optimizada y garantizar la mejor posibilidad de supervivencia, así como permitir una comparación fiable de las futuras intervenciones terapéuticas de investigación que formen parte de futuros estudios observacionales o de ensayos clínicos. Abstract Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, that was first recognized in Wuhan, China, in December 2019. Currently, the World Health Organization (WHO) has defined the infection as a global pandemic and there is a health and social emergency for the management of this new infection. While most people with COVID-19 develop only mild or uncomplicated illness, approximately 14% develop severe disease that requires hospitalization and oxygen support, and 5% require admission to an intensive care unit. In severe cases, COVID-19 can be complicated by the acute respiratory distress syndrome (ARDS), sepsis and septic shock, and multiorgan failure. This consensus document has been prepared on evidence-informed guidelines developed by a multidisciplinary panel of health care providers from four Spanish scientific societies (Spanish Society of Intensive Care Medicine [SEMICYUC], Spanish Society of Pulmonologists [SEPAR], Spanish Society of Emergency [SEMES], Spanish Society of Anesthesiology, Reanimation, and Pain [SEDAR]) with experience in the clinical management of patients with COVID-19 and other viral infections, including SARS, as well as sepsis and ARDS. The document provides clinical recommendations for the noninvasive respiratory support (noninvasive ventilation, high flow oxygen therapy with nasal cannula) in any patient with suspected or confirmed presentation of COVID-19 with acute respiratory failure. This consensus guidance should serve as a foundation for optimized supportive care to ensure the best possible chance for survival and to allow for reliable comparison of investigational therapeutic interventions as part of randomized controlled trials.


MERS CoV: A trigger for healthcare transformation


title: On programmed ribosomal frameshifting: the alternative proteomes

text: Frameshifting results from two main mechanisms: genomic insertions or deletions (indels) or programmed ribosomal frameshifting. Whereas indels can disrupt normal protein function, programmed ribosomal frameshifting can result in dual-coding genes, each of which can produce multiple functional products. Here, I summarize technical advances that have made it possible to identify programmed ribosomal frameshifting events in a systematic way. The results of these studies suggest that such frameshifting occurs in all genomes, and I will discuss methods that could help characterize the resulting alternative proteomes.


title: Retrospective Validation of a Metagenomic Sequencing Protocol for Combined Detection of RNA and DNA Viruses Using Respiratory Samples from Pediatric Patients

text: Viruses are the main cause of respiratory tract infections. Metagenomic next-generation sequencing (mNGS) enables unbiased detection of all potential pathogens. To apply mNGS in viral diagnostics, sensitive and simultaneous detection of RNA and DNA viruses is needed. Herein, were studied the performance of an in-house mNGS protocol for routine diagnostics of viral respiratory infections with potential for automated pan-pathogen detection. The sequencing protocol and bioinformatics analysis were designed and optimized, including exogenous internal controls. Subsequently, the protocol was retrospectively validated using 25 clinical respiratory samples. The developed protocol using Illumina NextSeq 500 sequencing showed high repeatability. Use of the National Center for Biotechnology Information’s RefSeq database as opposed to the National Center for Biotechnology Information’s nucleotide database led to enhanced specificity of classification of viral pathogens. A correlation was established between read counts and PCR cycle threshold value. Sensitivity of mNGS, compared with PCR, varied up to 83%, with specificity of 94%, dependent on the cutoff for defining positive mNGS results. Viral pathogens only detected by mNGS, not present in the routine diagnostic workflow, were influenza C, KI polyomavirus, cytomegalovirus, and enterovirus. Sensitivity and analytical specificity of this mNGS protocol were comparable to PCR and higher when considering off-PCR target viral pathogens. One single test detected all potential viral pathogens and simultaneously obtained detailed information on detected viruses.


title: Microwave-Generated Steam Decontamination of N95 Respirators Utilizing Universally Accessible Materials

text: The SARS-CoV-2 pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect healthcare providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1100W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log(10) plaque forming unit (PFU) (99.9999%) and a minimum 5-log(10) PFU (99.999%) reduction after a single three-minute microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.


Management of surgical lung cancer patients during the COVID‐19 pandemic in the financially and resource strained Greek health care system


title: Epidemic Keratoconjunctivitis in India: Trend Analysis and Implications for Viral Outbreaks

text: PURPOSE: To describe the correlation between the temporal pattern of presentation of acute epidemic keratoconjunctivitis (EKC) of presumed adenoviral etiology with meteorological parameters such as environmental temperature, rainfall, humidity, and wind speed. METHODS: This cross-sectional hospital-based study included 2,408,819 patients presenting between August 2010 and February 2020. Patients with a clinical diagnosis of EKC in at least one eye were included as cases. A smaller cohort of patients with acute (≤1 week) presentation hailing from the district of Hyderabad during the calendar years 2016–2019 was used to perform correlation analysis with the local environmental temperature, rainfall, humidity, and wind speed (data obtained from the Telangana State Development and Planning Society). RESULTS: Overall, 21,196 (0.87%) patients were diagnosed with EKC, of which 19,203 (90.6%) patients had acute onset; among which the cohort from the district of Hyderabad included 1,635 (8.51%) patients. The mean monthly prevalence in this cohort was 0.89% with a peak prevalence in April (1.09%). The environmental parameters of rainfall (r(2) = 0.47/P = 0.0131), humidity (r(2) = 0.65/P = 0.0014), and wind speed (r(2) = 0.56/P = 0.0047) were significantly negatively correlated with the temporal pattern of EKC in the population. There was no visible trend or significant correlation seen with temperature (r(2) = 0.08/P = 0.3793). CONCLUSION: Contrary to popular belief, epidemic viral infections like EKC may not be affected by temperature, but rather by a complex interplay of other environmental factors such as humidity, rainfall, and wind speed. An increase in rainfall, wind speed, and humidity contributes to a lower prevalence of EKC cases during the year.


title: Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A Position Paper

text: Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of healthcare facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country's Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in healthcare settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies and healthcare professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR.


docid: ciqrsfpo

title: Un mundo, una salud: la epidemia por el nuevo coronavirus COVID-19


title: Mechanisms and Implications of Programmed Translational Frameshifting

text: While ribosomes must maintain translational reading frame in order to translate primary genetic information into polypeptides, cis-acting signals located on mRNAs represent higher order information content that can be used to fine tune gene expression. Classes of signals have been identified that direct a fraction of elongating ribosomes to shift reading frame by one base in the 5′ (−1) or 3′ (+1) direction. This is called programmed ribosomal frameshifting (PRF). Although mechanisms of PRF differ, a common feature is induction of ribosome pausing, which alters kinetic partitioning rates between in-frame and out-of-frame codons at specific “slippery” sequences. Many viruses use PRF to ensure synthesis of the correct ratios of virus-encoded proteins required for proper viral particle assembly and maturation, thus identifying PRF as an attractive target for antiviral therapeutics. In contrast, recent studies indicate that PRF signals may primarily function as mRNA destabilizing elements in cellular mRNAs. These studies suggest that PRF may be used to fine-tune gene expression through mRNA decay pathways. The possible regulation of PRF by non-coding RNAs is also discussed.


title: Medical and gastroenterological education during the COVID-19 outbreak

text: The outbreak of coronavirus disease 2019 has undeniably affected modalities of medical and gastroenterology training in all endemic areas. Indeed, the adoption of various distance-learning techniques has been mandatory to facilitate education and enhance skills such as problem-solving, self-directed learning, open communication and also holistic non-cognitive attributes such as adaptability and collaboration.


title: Antiviral Decoction of Isatidis Radix (板藍根 bǎn lán gēn) Inhibited Influenza Virus Adsorption on MDCK Cells by Cytoprotective Activity

text: The aim of this study is to elucidate how the Isatidis Radix (板藍根 bǎn lán gēn) tonic, as an aqueous mixture of hundreds of compositions, interrupts the infection of influenza viruses to their host cells. The efficacy of the tonic was evaluated and expressed as cell proliferation rate and plaque reduction rate in Madin-Darby Canine Kidney (MDCK) cells, against 3 strains of influenza A and B viruses. This boiling water (at 100°C) extract of Isatidis Radix (RIE) showed antiviral activity against influenza virus A and B. The concentration for 50% inhibition of influenza virus A replication (IC(50)) in MDCK cell was 12.6 mg/mL with a therapeutic index >8. When cells were incubated with RIE prior to virus adsorption, the numbers of viable cell were at least doubled compared to the numbers of virus control, RIE incubation after virus adsorption and RIE incubation with virus prior to adsorption, in both influenza virus A and B. Moreover, much less virus particles were spotted by scanning electron microscope (SEM) in the RIE pre-treated cells than the cells without RIE treatment. These results indicate the antiviral activity of RIE is mainly attributed to its host cell protection effect but not actions on virus or post-virus-adsorption interruption. Cell, but not virus, is more likely to be the action target of RIE.


title: Fibroblasts: The Unknown Sentinels Eliciting Immune Responses Against Microorganisms

text: Fibroblasts are present in all tissues but predominantly in connective tissues. Some of their functions include contractility, locomotion, collagen and elastin fiber production, and the regulation and degradation of the extracellular matrix. Also, fibroblasts act as sentinels to produce inflammatory mediators in response to several microorganisms. There is evidence that fibroblasts can synthesize toll-like receptors (TLRs), antimicrobial peptides, proinflammatory cytokines, chemokines, and growth factors, which are important molecules involved in innate immune response against microorganisms. Fibroblasts can express TLRs (TLR-1 to TLR-10) to sense microbial components or microorganisms. They can synthesize antimicrobial peptides, such as LL-37, defensins hBD-1, and hBD-2, molecules that perform antimicrobial activity. Also, they can produce proinflammatory cytokines, such as TNFα, INFγ, IL-6, IL-12p70, and IL-10; other chemokines, such as CCL1, CCL2, CCL5, CXCL1, CXCL8, CXCL10, and CX3CL1; and the growth factors granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) to induce and recruit inflammatory cells. According to their immunological attributes, we can conclude that fibroblasts are sentinel cells that recognize pathogens, induce the recruitment of inflammatory cells via cytokines and growth factors, and release antimicrobial peptides, complying with the characteristics of real sentinels.


title: Network-based analysis of comorbidities risk during an infection: SARS and HIV case studies

text: BACKGROUND: Infections are often associated to comorbidity that increases the risk of medical conditions which can lead to further morbidity and mortality. SARS is a threat which is similar to MERS virus, but the comorbidity is the key aspect to underline their different impacts. One UK doctor says "I’d rather have HIV than diabetes" as life expectancy among diabetes patients is lower than that of HIV. However, HIV has a comorbidity impact on the diabetes. RESULTS: We present a quantitative framework to compare and explore comorbidity between diseases. By using neighbourhood based benchmark and topological methods, we have built comorbidity relationships network based on the OMIM and our identified significant genes. Then based on the gene expression, PPI and signalling pathways data, we investigate the comorbidity association of these 2 infective pathologies with other 7 diseases (heart failure, kidney disorder, breast cancer, neurodegenerative disorders, bone diseases, Type 1 and Type 2 diabetes). Phenotypic association is measured by calculating both the Relative Risk as the quantified measures of comorbidity tendency of two disease pairs and the ϕ-correlation to measure the robustness of the comorbidity associations. The differential gene expression profiling strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response and statistically dysregulates a large number of genes, pathways and PPIs subnetworks in different pathologies such as chronic heart failure (21 genes), breast cancer (16 genes) and bone diseases (11 genes). HIV-1 induces comorbidities relationship with many other diseases, particularly strong correlation with the neurological, cancer, metabolic and immunological diseases. Similar comorbidities risk is observed from the clinical information. Moreover, SARS and HIV infections dysregulate 4 genes (ANXA3, GNS, HIST1H1C, RASA3) and 3 genes (HBA1, TFRC, GHITM) respectively that affect the ageing process. It is notable that HIV and SARS similarly dysregulated 11 genes and 3 pathways. Only 4 significantly dysregulated genes are common between SARS-CoV and MERS-CoV, including NFKBIA that is a key regulator of immune responsiveness implicated in susceptibility to infectious and inflammatory diseases. CONCLUSIONS: Our method presents a ripe opportunity to use data-driven approaches for advancing our current knowledge on disease mechanism and predicting disease comorbidities in a quantitative way. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-333) contains supplementary material, which is available to authorized users.


title: Simulation models for transmission of health care–associated infection: A systematic review

text: BACKGROUND: Health care–associated infections (HAIs) are a global health burden because of their significant impact on patient health and health care systems. Mechanistic simulation modeling that captures the dynamics between patients, pathogens, and the environment is increasingly being used to improve understanding of epidemiological patterns of HAIs and to facilitate decisions on infection prevention and control (IPC). The purpose of this review is to present a systematic review to establish (1) how simulation models have been used to investigate HAIs and their mitigation and (2) how these models have evolved over time, as well as identify (3) gaps in their adoption and (4) useful directions for their future development. METHODS: The review involved a systematic search and identification of studies using system dynamics, discrete event simulation, and agent-based model to study HAIs. RESULTS: The complexity of simulation models developed for HAIs significantly increased but heavily concentrated on transmission dynamics of methicillin-resistant Staphylococcus aureus in the hospitals of high-income countries. Neither HAIs in other health care settings, the influence of contact networks within a health care facility, nor patient sharing and referring networks across health care settings were sufficiently understood. CONCLUSIONS: This systematic review provides a broader overview of existing simulation models in HAIs to identify the gaps and to direct and facilitate further development of appropriate models in this emerging field.


title: The serial interval of COVID-19 from publicly reported confirmed cases

text: We estimate the distribution of serial intervals for 468 confirmed cases of COVID-19 reported in 93 Chinese cities by February 8, 2020. The mean and standard deviation are 3.96 (95% CI 3.53–4.39) and 4.75 (95% CI 4.46–5.07) days, respectively, with 12.6% of reports indicating pre-symptomatic transmission.


title: Representation of molecular structures with persistent homology for machine learning applications in chemistry

text: Machine learning and high-throughput computational screening have been valuable tools in accelerated first-principles screening for the discovery of the next generation of functionalized molecules and materials. The application of machine learning for chemical applications requires the conversion of molecular structures to a machine-readable format known as a molecular representation. The choice of such representations impacts the performance and outcomes of chemical machine learning methods. Herein, we present a new concise molecular representation derived from persistent homology, an applied branch of mathematics. We have demonstrated its applicability in a high-throughput computational screening of a large molecular database (GDB-9) with more than 133,000 organic molecules. Our target is to identify novel molecules that selectively interact with CO(2). The methodology and performance of the novel molecular fingerprinting method is presented and the new chemically-driven persistence image representation is used to screen the GDB-9 database to suggest molecules and/or functional groups with enhanced properties.


title: Tandem mass tag-based quantitative proteomic analysis of lycorine treatment in highly pathogenic avian influenza H5N1 virus infection

text: Highly pathogenic H5N1 influenza viruses (HPAIV) cause rapid systemic illness and death in susceptible animals, leading to a disease with high morbidity and mortality rates. Although vaccines and drugs are the best solution to prevent this threat, a more effective treatment for H5 strains of influenza has yet to be developed. Therefore, the development of therapeutics/drugs that combat H5N1 influenza virus infection is becoming increasingly important. Lycorine, the major component of Amaryllidaceae alkaloids, exhibits better protective effects against A/CK/GD/178/04 (H5N1) (GD178) viruses than the commercial neuraminidase (NA) inhibitor oseltamivir in our prior study. Lycorine demonstrates outstanding antiviral activity because of its inhibitory activity against the export of viral ribonucleoprotein complexes (vRNPs) from the nucleus. However, how lycorine affects the proteome of AIV infected cells is unknown. Therefore, we performed a comparative proteomic analysis to identify changes in protein expression in AIV-infected Madin-Darby Canine Kidney cells treated with lycorine. Three groups were designed: mock infection group (M), virus infection group (V), and virus infection and lycorine-treated after virus infection group (L). The multiplexed tandem mass tag (TMT) approach was employed to analyze protein level in this study. In total, 5,786 proteins were identified from the three groups of cells by using TMT proteomic analysis. In the V/M group, 1,101 proteins were identified, of which 340 differentially expressed proteins (DEPs) were determined during HPAIV infection; among the 1,059 proteins identified from the lycorine-treated group, 258 proteins presented significant change. Here, 71 proteins showed significant upregulation or downregulation of expression in the virus-infected/mock and virus-infected/lycorine-treated comparisons, and the proteins in each fraction were functionally classified further. Interestingly, lycorine treatment decreased the levels of the nuclear pore complex protein 93 (Nup93, E2RSV7), which is associated with nuclear–cytoplasmic transport. In addition, Western blot experiments confirmed that the expression of Nup93 was significantly downregulated in lycorine treatment but induced after viral infection. Our results may provide new insights into how lycorine may trap vRNPs in the nucleus and suggest new potential therapeutic targets for influenza virus.


title: Can the summer temperature drop COVID-19 cases?

text: Abstract Objective In spite of huge global, national and local preventive measures including travel restriction, social distancing and quarantines, outbreak of novel coronavirus SARS-CoV-2 develops COVID-19 worldwide pandemic. SARS-CoV-2 emerging from Wuhan, China took only three months to cover > 200 countries worldwide by infecting more than 2.4 million people and killing more than 150000 people. Though, this infection at the early stage creates seasonal flu-like symptoms with a higher illness, it eventually causes a higher mortality. Epidemiological studies not only find the causes of many health issues, but also suggest preventive measures. This study aimed to see the link between environment temperature and COVID-19 cases. Study design The monthly average environment temperature (MAET) and various COVID-19 cases of a country were collected, and analyzed to see the relationship between these parameters. Methods Univariate analysis and statistical modeling were used to determine the relationship between environment temperature and different COVID-19 cases. Results This study found that the majorities of the countries having higher COVID-19 cases are located in the higher latitude (colder region) in the globe. As of 20th April data available, statistical analyses by various methods have found that strong negative correlations with statistical significance exist between MAET and several COVID-19 cases including total cases, active cases and cases per million of a country [Spearman correlation coefficients were -0.45, -0.42, and -0.50 for total cases, active cases and cases/per million, respectively]. Analysis by statistical log-linear regression model further supports that the chance of COVID-19 patients is fewer in warmer countries than in colder countries. Conclusion This pilot study proposes that cold environment may be an additional risk factor for COVID-19 cases.


title: The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease

text: Abstract Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.


title: A simple remote nutritional screening tool and practical guidance for nutritional care in primary practice during the COVID-19 pandemic

text: Challenging periods like the COVID-19 pandemic require fast and efficient adaptations of the healthcare system. It is vital that every patient has access to nutritional care as a part of primary healthcare services, even if social distancing measures are adopted. Therefore, we propose a simple remote nutritional screening tool and practical guidance for nutritional care in primary practice, and their implementation into telemedicine processes and digital platforms suitable for healthcare providers. The acronym for the tool is R-MAPP, as for Remote – Malnutrition APP, while the tool will be available also as an app. This protocol consists of two simple validated clinical tools for identifying nutritional risk and loss of muscle mass and function –Malnutrition Universal Screening Tool (‘MUST’) and SARC-F (5-item questionnaire: Strength, Assistance with walking, Rise from a chair, Climb stairs and Falls) - and additional practical guidance on nutritional interventions for family physicians.


docid: khqvezmu

title: Impact of a hospital-wide hand hygiene promotion strategy on healthcare-associated infections

text: BACKGROUND: During the Severe Acute Respiratory Syndrome (SARS) outbreak, high compliance in healthcare workers to hand hygiene was primarily driven by fear. However, the post-SARS period confirmed that this practice was not sustainable. At the Singapore General Hospital, a 1,600-bedded acute tertiary care hospital, the hand hygiene program was revised in early 2007 following Singapore's signing of the pledge to the World Health Organization (WHO) "Clean Care is Safer Care" program. FINDINGS: A multi-prong approach was used in designing the hand hygiene program. This included system change; training and education; evaluation and feedback; reminders in the workplace; and institutional safety climate. Hand hygiene compliance rate improved from 20% (in January 2007) to 61% (2010). Improvement was also seen annually in the compliance to each of the 5 moments as well as in all staff categories. Healthcare-associated MRSA infections were reduced from 0.6 (2007) to 0.3 (2010) per 1000 patient-days. CONCLUSIONS: Leadership's support of the program evidenced through visible leadership presence, messaging and release of resources is the key factor in helping to make the program a true success. The hospital was recognised as a Global Hand Hygiene Expert Centre in January 2011. The WHO multi-prong interventions work in improving compliance and reducing healthcare associated infections.


title: Socio-environmental exposures and health outcomes among persons with sickle cell disease

text: There is much variability in the expression of sickle cell disease (SCD) and recent works suggest that environmental and social factors may also influence this variability. This paper aims to use geographic information systems technology to examine the association between socio-environmental exposures and health outcomes in all persons who have attended or currently attend the Sickle Cell Unit in Jamaica. Rural patients presented for clinical care at older ages and had less annual visits to clinic. Persons travelled relatively long distances to seek SCD care and those travelling longer had less health maintenance visits. Urban patients had a higher prevalence of significant pain crises (69.4% vs. 55.8%, p value<0.001) and respiratory events (21.2% vs. 14%, p value<0.001). Prevalence of leg ulcers did not vary between rural and urban patients but was higher in males than in females. Females also had lower odds of having respiratory events but there was no sex difference in history of painful crises. Persons with more severe genotypes lived in higher poverty and travelled longer for healthcare services. Persons in areas with higher annual rainfall, higher mean temperatures and living farther from factories had less painful crises and respiratory events. The paper highlights a need for better access to healthcare services for Jamaicans with SCD especially in rural areas of the island. It also reports interesting associations between environmental climatic exposures and health outcomes.


title: Efficacy and safety of withholding antimicrobial treatment in children with cancer, fever and neutropenia, with a demonstrated viral respiratory infection: a randomized clinical trial

text: Abstract Objectives To determine efficacy and safety of withholding antimicrobials in children with cancer, fever and neutropenia (FN) with a demonstrated respiratory viral infection. Methods Prospective, multicentre, randomized study in children presenting with FN at five hospitals in Santiago, Chile, evaluated at admission for diagnosis of bacterial and viral pathogens including PCR-microarray for 17 respiratory viruses. Children positive for a respiratory virus, negative for a bacterial pathogen and with a favourable evolution after 48 h of antimicrobial therapy were randomized to either maintain or withhold antimicrobials. Primary endpoint was percentage of episodes with uneventful resolution. Secondary endpoints were days of fever/hospitalization, bacterial infection, sepsis, admission to paediatric intensive care unit (PICU) and death. Results A total of 319 of 951 children with FN episodes recruited between July 2012 and December 2015 had a respiratory virus as a unique identified microorganism, of which 176 were randomized, 92 to maintain antimicrobials and 84 to withdraw. Median duration of antimicrobial use was 7 days (range 7–9 days) versus 3 days (range 3–4 days), with similar frequency of uneventful resolution (89/92 (97%) and 80/84 (95%), respectively, not significant; OR 1.48; 95% CI 0.32–6.83, p 0.61), and similar number of days of fever (2 versus 1), days of hospitalization (6 versus 6) and bacterial infections throughout the episode (2%–1%), with one case of sepsis requiring admission to PICU in the group that maintained antimicrobials, without any deaths. Conclusions The reduction of antimicrobials in children with FN and respiratory viral infections, based on clinical and microbiological/molecular diagnostic criteria, should favour the adoption of evidence-based management strategies in this population.


title: Not all worries were created equal: The case of COVID-19 anxiety

text: Abstract Objectives To investigate possible differences in COVID-19 related anxiety based on previous theories in social psychology. Study Design Cross-sectional online questionnaire delivered via crowdworking platform. Method 407 (120 males and 287 females) adults (age >18) from the United Kingdom answered the State-Trait Anxiety Inventory (STAI) "in light of the COVID-19 situation", followed by three health and three financial anxiety items. Results Our findings imply that: women are more anxious than men; people are more anxious about others than about themselves; their anxiety about relatives is higher than about strangers; and - that anxiety about health is higher than about financial issues. Conclusions We suggest that these preliminary findings should be further investigated to help policymakers improve both their treatment of pandemic-related anxiety and their messages.


Re-emergence of neuroinfectiology


title: Development of a SYBR green I-based duplex real-time fluorescence quantitative PCR assay for the simultaneous detection of porcine epidemic diarrhea virus and porcine circovirus 3

text: Abstract The development of a rapid, specific, and sensitive SYBR Green I-based duplex real-time quantitative PCR assay is described for the simultaneous detection of porcine epidemic diarrhea virus (PEDV) and porcine circovirus type 3 (PCV3). The assay specifically detected PEDV and PCV3, with no fluorescence detected for other non-targeted pig pathogens. The assay showed a good linear relationship, and the limits of detection for this assay were 34.6 copies/μL and 61.2 copies/μL for PEDV and PCV3, respectively. The assay exhibited high repeatability and reproducibility, with intra-assay and inter-assay variation coefficients less than 2.0%. A clinical evaluation using intestinal tissue and fecal samples from piglets suffering from diarrhea at different pig farms in China revealed that the singular infection rates of PEDV and PCV3 were 43.94% (29/66) and 16.67% (11/66), respectively, while the co-infection rate of PCV3 with PEDV was 27.27% (18/66). The results indicate this assay is a rapid and reliable diagnostic tool for PEDV and PCV3 monitoring and surveillance in the field, and provides technical support for the quantitative detection of clinical samples infected or co-infected with PEDV and PCV3.


title: Radiology Residency Preparedness and Response to the COVID-19 Pandemic

text: Abstract This article provides a guideline for radiology residency programs to prepare and respond to the impact of COVID-19, by offering specific examples from three programs, and provides a list of resources for distance learning and maintaining well-being.


title: Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

text: BACKGROUND: Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. RESULTS: Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. CONCLUSIONS: Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is connected to apoptosis, a finding that deserves further investigation.


Elites can take care of themselves — Comment on COVID-19: the rude awakening for the political elite in low-income and middle-income countries


docid: aonqthxn

title: Increased ozone levels during the COVID-19 lockdown: Analysis for the city of Rio de Janeiro, Brazil

text: The first COVID-19 case in Brazil was confirmed on February 25, 2020. Partial lockdown measures came into force in the city of Rio de Janeiro, Brazil, on March 23. While CO and NO(2) levels showed significant reductions, PM(10) levels were only reduced in the first partial lockdown week. By contrast, ozone levels increased in all studied locations. In this study, the factors leading to this behavior were analyzed. Monitoring data obtained at two automatic monitoring stations showed higher ratios between non-methane hydrocarbons and nitrogen oxides (NMHC/NO(x)) during the partial lockdown (up to 37.3%). The increase in ozone concentrations during the social distancing measures could be attributed to the increase in NMHC/NO(x) ratios since atmospheric chemistry in Rio de Janeiro is under VOC-controlled conditions. However, the increase was higher when air masses arrived from the industrial areas, not only because of the higher NMHC/NO(x) ratios, but also because the reactivity of VOC was highly increased by these air masses, which are rich in aromatic compounds.


title: Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients

text: Abstract Objectives This study aimed to assess the immediate stress and psychological impact experienced by quarantined patients undergoing hemodialysis and university hospital workers who treated patients Middle East respiratory syndrome (MERS) during its outbreak. Design The group of subjects consisted of 1800 hospital practitioners and 73 quarantined patients undergoing hemodialysis. The Impact of Events Scale–Revised (IES-R) was administered to the practitioners twice, once during the hospital shutdown and again one month after the shutdown. The Mini International Neuropsychiatric Interview and Hospital Anxiety and Depression Scale were administered to patients undergoing hemodialysis. Results During the initial stages of the MERS outbreak, healthcare workers who performed MERS-related tasks scored significantly higher on the total IES-R and its subscales. In the second assessment of the high-risk group, the sleep and numbness subscale scores from the IES-R differed depending on the implementation of home quarantine, and the intrusion subscale scores differed depending on the performance of MERS-related tasks. Conclusion Medical staff that performed MERS-related tasks showed the highest risk for post-traumatic stress disorder symptoms even after time had elapsed. The risk increased even after home quarantine. Prompt and continuous psychiatric intervention is needed in high mortality infectious disease outbreaks.


title: Epidemiology and Clinical Presentations of Respiratory Syncytial Virus Subgroups A and B Detected with Multiplex Real-Time PCR

text: Respiratory syncytial virus (RSV) is one of the most important pathogenic infections of children and requires in-depth research worldwide, and especially in developing countries. We used a novel multiplex real-time PCR to test 5483 patients (≤ 14 years old) hospitalized with respiratory illness in Guangzhou, China, over a 3-year period. Of these patients, 729 were positive for RSV-A (51.2%, 373/729) or RSV-B (48.8%, 356/729), but none was infected with both viruses. Two seasonal peaks in total RSV were detected at the changes from winter to spring and from summer to autumn. RSV-B was dominant in 2013 and RSV-A in 2015, whereas RSV-A and RSV-B cocirculated in 2014. The clinical presentations of 645 RSV-positive patients were analyzed. Bronchiolitis, dyspnea, coryza, vomiting, poor appetite, and diarrhea occurred more frequently in RSV-A-positive than RSV-B-positive patients, whereas chill, headache, myalgia, debility, and rash etc. were more frequent in RSV-B-positive than RSV-A-positive patients, suggesting specific clinical characteristics for RSV-A and RSV-B. Coinfectons with other pathogens were common and diverse. Bronchiolitis, fever (≥ 38°C), and poor appetite were more frequent in patients with single RSV infections than in coinfected patients, suggesting the key pathogenic activity of RSV. Analysis of the relationships between the comparative viral load and clinical presentations showed significant differences in bronchiolitis, fever (≥ 38°C), and rash etc. among patients with different viral loads. This study provides a novel rapid method for detecting RSV subgroups, and provides new insights into the epidemiology and clinical implications of RSV.


Acute Aortic Thrombosis Revealing a COVID-19 Infection


title: The Symmetry of Viral Sialic Acid Binding Sites—Implications for Antiviral Strategies

text: Virus infections are initiated by the attachment of the viral particle to protein or carbohydrate receptors on the host cell. Sialic acid-bearing glycan structures are prominently displayed at the cell surface, and, consequently, these structures can function as receptors for a large number of diverse viruses. Structural biology research has helped to establish the molecular bases for many virus–sialic acid interactions. Due to the icosahedral 532 point group symmetry that underlies many viral capsids, the receptor binding sites are frequently arranged in a highly symmetric fashion and linked by five-fold, three-fold, or two-fold rotation axes. For the inhibition of viral attachment, one emerging strategy is based on developing multivalent sialic acid-based inhibitors that can simultaneously engage several of these binding sites, thus binding viral capsids with high avidity. In this review, we will evaluate the structures of non-enveloped virus capsid proteins bound to sialylated glycan receptors and discuss the potential of these structures for the development of potent antiviral attachment inhibitors.


title: Traditional and Virtual Congress Meetings During the COVID-19 Pandemic and the Post-COVID-19 Era: Is it Time to Change the Paradigm?

text: The speed and reach of the COVID-19 pandemic have forced rapid changes in how we conduct medical practice and research. The rapid evolution in how scientific meetings are conducted may have long-term benefits. A new reality in which technology and sociality are merged may offer a more engaging and adaptable scientific congress experience with more flexible and dynamic use of content modulated to the needs of each attendee.


title: Viral Anticytokine Strategies

text: Abstract Viruses have evolved numerous mechanisms to evade the immune response, including proteins that target the function of cytokines. This article provides an overview of the different strategies used by viruses to block the induction of cytokines and immune signals triggered by cytokines. Examples of virus evasion proteins are presented, such as intracellular proteins that block signal transduction and immune activation mechanisms, secreted proteins that mimic cytokines, or viral decoy receptors that inhibit the binding of cytokines to their cognate receptors. Virus-encoded proteins that target cytokines play a major role in immune modulation, and their contributions to viral pathogenesis, promoting virus replication or preventing immunopathology, are discussed.


title: Survival of influenza A virus on contaminated student clothing

text: The role of contaminated clothing in the transmission of influenza A virus during an epidemic period was investigated by examining the recovery of infectious influenza virus from experimentally virus-contaminated clothing, which had been subejected to routine wearing and washing for several months or years. The amount of infectious virus recovered from the nine types of clothing decreased with time and was shown to differ widely between clothing samples, when the contaminated clothing samples were maintained in uncovered glass Petri dishes in a safety cabinet under air blowing. These results indicate a dependence of virus transmissibility on the nature of the contaminated clothes. The difference in recovery was shown to have no significant correlation with the thickness or the materials of the clothing; however, a correlation was observed with the residual amount of water in the deposited virus preparation on the test clothing.


title: A Biomarker-Based Approach to Infectious Disease in the Pediatric Emergency Department

text: In modern pediatric emergency medicine, biomarker-based assays that enable quick bedside diagnostics and subsequent disease management can be valuable. There is a growing need for novel, disease-specific biomarkers that can improve the outcome of pediatric infectious diseases commonly encountered in the emergency department (ED). Viral respiratory infections, central nervous system infections, sepsis, and septic shock are acute disease states frequently encountered in the ED. In this review, we describe a host of novel biomarkers, including a diverse set of cytokines, chemokines, and nitric oxide–based metabolites. Based on disease pathophysiology, a rationale is provided for a molecular- or biomarker-based approach in the ED. Throughout this review, emphasis is placed on diagnostic rapidity because this relates directly to timeliness and quality of care in a busy ED. Once the biomarkers become more clinically available, in a rapid ED setting as bedside point-of-care assays, quality of care will be enhanced, not only by means of diagnostics but also in prognosticating severity of illness.


title: Association of bronchoalveolar lavage yield with chest computed tomography findings and symptoms in immunocompromised patients

text: INTRODUCTION: Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) is a common procedure performed in immunocompromised patients with undiagnosed pulmonary pathology. Identifying patients with the highest potential diagnostic yield may help to avoid morbidity in patients unlikely to benefit from the procedure. We sought to determine which patient factors, specifically chest computed tomography (CT) findings, affected diagnostic yield of BAL. METHODS: Retrospective chart review of immunocompromised patients who underwent FOB with BAL from 01/01/2010 to 12/31/2011 at an academic medical center was performed. The lung lobe lavaged, characteristics of pulmonary infiltrate on radiograph, patient symptoms, and diagnostic yield were collected. A positive diagnostic yield was defined as a positive microbiological culture, finding on cytopathologic staining, diffuse alveolar hemorrhage, alveolar eosinophilia or a positive immunologic or nucleic acid assay. RESULTS: The overall diagnostic yield was 52.6%. Infiltrates that were predominantly reticular or nodular by CT had a lower diagnostic yield than predominantly consolidated, ground-glass, or tree-in-bud infiltrates (36.5% vs. 61.2%, P = 0.0058). The diagnostic yield was significantly improved in patients with both fever and chest symptoms compared to patients without symptoms (61.3% vs. 29.6%, P = 0.0066). CONCLUSION: CT findings of reticular and nodular infiltrates portend a worse diagnostic yield from BAL than those that are alveolar in nature. Symptomatic patients are more likely to have diagnostic FOB with BAL than asymptomatic patients.


title: Chapter 24 Wastewater Treatment and Biosolids Reuse

text: Publisher Summary The primary goal of wastewater treatment is the removal and degradation of organic matter under controlled conditions. This chapter describes the nature and modern treatment of waste water, land applications of waste water, and methods of land applications of biosolids and animal wastes. The amount of organic matter in domestic wastes determines the degree of required biological treatment. Various tests are used to assess the amount of organic matter: biochemical oxygen demand (BOD), chemical oxygen demand (COD), and total organic carbon (TOC). The complete sewage treatment comprises three major steps: primary, secondary, and tertiary treatment. Tertiary treatment processes involving physicochemical processes can be effective in reducing the concentration of pathogens. The treated domestic wastewater may be disposed of via land application for crop irrigation or as a means of additional treatment and disposal through the three basic methods that include low-rate irrigation, overland flow, and high-rate infiltration.


title: Clinical characteristics of non‐ICU hospitalized patients with coronavirus disease 2019 and liver injury: A retrospective study

text: BACKGROUND & AIMS: Coronavirus disease 2019 (COVID‐19) has raised world concern for global epidemic since December, 2019. Limited data are available for liver function in COVID‐19 patients. We aimed to investigate the risk factors related to liver injury in the COVID‐19 patients. METHODS: A retrospective study was performed in non‐ICU Ward at Jinyintan Hospital from February 2, 2020 to February 23, 2020. Consecutively confirmed COVID‐19 discharged cases were enrolled. The clinical characteristics of patients with liver injury and without liver injury were compared. RESULTS: A total of 79 COVID‐19 patients were included. 31.6%, 35.4% and 5.1% COVID‐19 patients had elevated levels of alanine transaminase (ALT), aspartate aminotransferase (AST) and bilirubin respectively. Median value of ALT, AST and bilirubin for entire cohort was 36.5 (17.5 ~ 71.5) U/L, 34.5 (25.3 ~ 55.3) U/L and 12.7 (8.1 ~ 15.4) mmol/L respectively. There were no significant differences in age, previous medical history and symptoms between the two groups. Males were more likely to have liver injury when infected with COVID‐19 (P < .05); compared with patients without liver injury, patients with liver injury had increased levels of white blood cell counts, neutrophils, CRP and CT score (P < .05) and had a longer length of stay (P < .05). Logistic regression analyses suggested that the extent of pulmonary lesions on CT was a predictor of liver function damage (P < .05). CONCLUSIONS: Liver injury is common in non‐ICU hospitalized COVID‐19 patients. It may be related to systemic inflammation. Intense monitoring and evaluation of liver function in patients with severe pulmonary imaging lesions should be considered.


title: Steroid induced osteonecrosis: An analysis of steroid dosing risk

text: Abstract Osteonecrosis is a serious condition involving bone destruction that frequently requires surgical treatment to rebuild the joint. While there is an abundance of literature documenting corticosteroid related osteonecrosis, there is no consensus as to the relative risk of osteonecrosis after administration of steroids via parenteral, oral, topical, inhaled and other routes. This risk is an important prognostic indicator because identification and conservative intervention can potentially reduce morbidity associated with aggressive surgical treatment of osteonecrosis. This paper provides insight into establishing guidelines related to the risk of developing osteonecrosis as a result of corticosteroid use. Case studies, retrospective studies and prospective studies in humans on different corticosteroids and varied dosages were assessed. Most cases of osteonecrosis are secondary to systemically administered corticosteroids and/or high dose daily therapy, particularly in patients with underlying comorbidities including connective tissue diseases, hyperlipidemia, or previous trauma. Previous case reports of osteonecrosis related to inhaled or topical use of steroids are complicated by the fact that in the great majority of cases, the patients are also treated with systemic steroids prior to the development of osteonecrosis. Based on the literature, a set of recommendations regarding the risk of osteonecrosis in patients on steroids was formulated.


title: Mouse hepatitis virus nsp14 exoribonuclease activity is required for resistance to innate immunity

text: Coronaviruses (CoV) are positive-sense RNA viruses that infect numerous mammalian and avian species and are capable of causing severe and lethal disease in humans. CoVs encode several innate immune antagonists that interact with the host innate immune response to facilitate efficient viral replication. CoV non-structural protein 14 (nsp14) encodes 3'-to-5' exoribonuclease activity (ExoN), which performs a proofreading function and is required for high-fidelity replication. Outside of the order Nidovirales, arenaviruses are the only RNA viruses that encode an ExoN, which functions to degrade dsRNA replication intermediates. In this study, we tested the hypothesis that CoV ExoN may also function to antagonize the innate immune response. We demonstrate that viruses lacking ExoN activity [ExoN(-)] are sensitive to cellular pretreatment with interferon beta (IFN-β) in a dose-dependent manner. In addition, ExoN(-) virus replication was attenuated in wild-type bone marrow-derived macrophages (BMMs) and partially restored in interferon alpha/beta receptor deficient (IFNAR-/-) BMMs. ExoN(-) virus replication did not result in IFN-β gene expression, and in the presence of an IFN-β-mediated antiviral state, ExoN(-) viral RNA levels were not substantially reduced relative to untreated. However, ExoN(-) virus generated from IFN-β pretreated cells had reduced specific infectivity and decreased relative fitness, suggesting that ExoN(-) virus generated during an antiviral state is less viable to establish a subsequent infection. Overall, our data suggest MHV ExoN activity is required for resistance to the innate immune response and antiviral mechanisms affecting the viral RNA sequence and/or an RNA modification act on viruses lacking ExoN activity.


docid: ynkclvvx

title: Guarding the frontiers: the biology of type III interferons

text: Type III interferons (IFNs) or IFN-λs regulate a similar set of genes as type I IFNs, but whereas type I IFNs act globally, IFN-λs primarily target mucosal epithelial cells and protect them against the frequent viral attacks that are typical for barrier tissues. IFN-λs thereby help to maintain healthy mucosal surfaces through immune protection, without the significant immune-related pathogenic risk associated with type I IFN responses. Type III IFNs also target the human liver, with dual effects: they induce an antiviral state in hepatocytes, but specific IFN-λ4 action impairs the clearance of hepatitis C virus and could influence inflammatory responses. This constitutes a paradox that has yet to be resolved.


Author response to: Covid‐19‐related pancreatic injury


title: Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States

text: Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care.


title: Systematic review of the efficacy and safety of antiretroviral drugs against SARS, MERS or COVID‐19: initial assessment

text: INTRODUCTION: Several antiretroviral drugs are being considered for the treatment of COVID‐19, the disease caused by a newly identified coronavirus, (SARS‐CoV‐2). We systematically reviewed the clinical outcomes of using antiretroviral drugs for the prevention and treatment of coronaviruses and planned clinical trials. METHODS: Three databases were screened from inception to 30 March 2020 for studies reporting clinical outcomes of patients with SARS, MERS or COVID‐19 treated with antiretrovirals. RESULTS: From an initial screen of 433 titles, two randomized trials and 24 observational studies provided clinical outcome data on the use of antiretroviral drugs; most studies reported outcomes using LPV/r as treatment. Of the 21 observational studies reporting treatment outcomes, there were three studies among patients with SARS, six studies among patients with MERS and 12 studies among patients with COVID‐19. In one randomized trial 99 patients with severe COVID‐19 illness were randomized to receive LPV/r (400/100 mg twice a day) and 100 patients to standard of care for 14 days: LPV/r was not associated with a statistically significant difference in time to clinical improvement, although LPV/r given within 12 days of symptoms was associated with shorter time to clinical improvement; 28 day mortality was numerically lower in the LPV/r group (14/99) compared to the control group (25/100), but this difference was not statistically significant. The second trial found no benefit. The certainty of the evidence for the randomized trials was low. In the observational studies 3 out of 361 patients who received LPV/r died; the certainty of evidence was very low. Three studies reported a possible protective effect of LPV/r as post‐exposure prophylaxis. Again, the certainty of the evidence was very low due to uncertainty due to limited sample size. CONCLUSIONS: On the basis of the available evidence it is uncertain whether LPV/r and other antiretrovirals improve clinical outcomes or prevent infection among patients at high risk of acquiring COVID‐19.


title: Large-scale mortality shocks and the Great Irish Famine 1845–1852

text: This paper considers the consequences of a large scale mortality shock arising from a famine or epidemic for long run economic and demographic development. The Great Irish Famine of 1845–1852 is taken as a case-study and is incorporated as an exogenous mortality shock into the type of long-run unified growth theory pioneered by Galor and Weil (1999, 2000), and modelled by Lagerlöf (2003a,b) among others. Through calibration, the impact of such a mortality shock occurring on the cusp of a country's transition from a Malthusian to a Modern Growth regime is then depicted.


The role of percutaneous interventions in the management of lung cancer patients during the Covid‐19 pandemic


docid: sbppgkza

title: Lyme disease: Current issues, implications, and recommendations for tourism management

text: Lyme disease is a bacterial infection spread through the bite of an infected tick. In the last few decades, the number and spatial reach of new cases has increased globally and in the United States, Lyme disease is now the most commonly reported vector-borne disease. Despite this evolving public health crisis, there has been little-to-no discussion of the implications for tourism supply and demand. This paper reviews the scientific literature to identify Lyme disease risk factors and the implications for tourism management are discussed. The major contribution of this paper is a set of recommendations for tourism managers who may be tasked with mitigating the risks for visitors and employees as well as the potential impacts of Lyme disease on destination sustainability.


docid: qeawbhcu

title: Network pharmacological approach for elucidating the mechanisms of traditional Chinese medicine in treating COVID-19 patients

text: [Figure: see text]


From the ASCO20 Virtual meeting


title: Modulation of type I interferon induction by porcine reproductive and respiratory syndrome virus and degradation of CREB-binding protein by non-structural protein 1 in MARC-145 and HeLa cells

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is an emerged disease of swine characterized by negligible response of type I IFNs and viral persistence. We show that the PRRSV non-structural protein 1 (Nsp1) is the viral component responsible for modulation of IFN response. Nsp1 blocked dsRNA-induced IRF3 and IFN promoter activities. Nsp1 did not block phosphorylation and nuclear translocation of IRF3 but inhibited IRF3 association with CREB-binding protein (CBP) in the nucleus. While IRF3 was stable, CBP was degraded, and CBP degradation was proteasome-dependent, suggesting that CBP degradation is not due to the protease activity of Nsp1 but an intermediary is involved. Our data suggest that the Nsp1-mediated CBP degradation inhibits the recruitment of CBP for enhanceosome assembly, leading to the block of IFN response. CBP degradation is a novel strategy for viral evasion from the host response, and Nsp1 may form a new class of viral antagonists for IFN modulation.


title: Isolation and recombinant analysis of variants of porcine epidemic diarrhea virus strains from Beijing, China

text: Porcine epidemic diarrhea virus (PEDV) is a highly infectious virus infecting pigs with high morbidity, especially for newborn piglets. Several PEDV strains were isolated from the intestinal tracts of diarrheic piglets from the Beijing area, China. Sequencing of the whole-genome of the PEDV isolates (GenBank numbers MG546687-MG546690) yielded sequences of 28033–28038 nt. The phylogenetic tree revealed that these strains from the Beijing area belonged to group II, while the vaccine strain, CV777, belonged to group I. We also determined the genetic correlation between these strains and CV777 strain. However, it showed that these strains in the Beijing area had unique mutations. The sequence identity of PEDV strains showed that these strains are most similar to these strains LZW, CH/JX-1/2013, USAIllinois972013, USAKansas1252014, CH/GDZQ/2014, SHQPYM2013, AJ1102, CHZMDZY11, KoreaK14JB01, and CHYJ130330, respectively. The possible recombination events indicate that PEDV in this studies were possibly recombinant strain formed by parent strains USAIllinois972013, KoreaK14JB01, CHYJ130330, and CHZMDZY11. These PEDV strains has been genetic recombination and mutations. The variant strains characterized in this study help to the evolutionary analysis of PEDV.


title: 6. Asthma: Factors underlying inception, exacerbation, and disease progression

text: Asthma is a heterogeneous disorder that is characterized by variable airflow obstruction, airway inflammation and hyperresponsiveness, and reversibility either spontaneously or as a result of treatment. Multiple causes no doubt exist for both its inception and symptom exacerbation once the disease is established. Factors underlying inception can range from viral respiratory tract infections in infancy to occupational exposures in adults. Factors underlying asthma exacerbations include allergen exposure in sensitized individuals, viral infections, exercise, irritants, and ingestion of nonsteroidal anti-inflammatory agents among others. Exacerbating factors might include one or all of these exposures and vary both among and within patients. Asthma treatment is determined to a large extent after an assessment of severity, which can be variable over time and assessed in 2 domains: impairment (current) and risk (long-term consequences). Unfortunately, despite the availability of effective therapies, suboptimal asthma control exists in many patients on a worldwide basis. The future development of novel therapies and treatment paradigms should address these disparities.


title: Transmission genetics of drug-resistant hepatitis C virus

text: Antiviral development is plagued by drug resistance and genetic barriers to resistance are needed. For HIV and hepatitis C virus (HCV), combination therapy has proved life-saving. The targets of direct-acting antivirals for HCV infection are NS3/4A protease, NS5A phosphoprotein and NS5B polymerase. Differential visualization of drug-resistant and -susceptible RNA genomes within cells revealed that resistant variants of NS3/4A protease and NS5A phosphoprotein are cis-dominant, ensuring their direct selection from complex environments. Confocal microscopy revealed that RNA replication complexes are genome-specific, rationalizing the non-interaction of wild-type and variant products. No HCV antivirals yet display the dominance of drug susceptibility shown for capsid proteins of other viruses. However, effective inhibitors of HCV polymerase exact such high fitness costs for drug resistance that stable genome selection is not observed. Barriers to drug resistance vary with target biochemistry and detailed analysis of these barriers should lead to the use of fewer drugs.


title: Pattern of liver injury in adult patients with COVID-19: a retrospective analysis of 105 patients

text: BACKGROUND: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown. METHODS: This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined. RESULTS: 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P < 0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge. CONCLUSIONS: Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.


title: Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

text: The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X(2) are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (K(i) in the micromolar range). The mode of action for all four compounds and both enzymes was demonstrated by molecular modeling and docking in the corresponding active sites. This knowledge gives new perspectives to Actinomycin D's action on tumors and suggests new avenues and molecules for medical applications.


title: Absolute quantitation of infectious salmon anaemia virus using different real-time reverse transcription PCR chemistries

text: Abstract Routine laboratory diagnosis of infectious salmon anaemia virus (ISAV) infection is primarily by reverse transcription polymerase chain reaction (RT-PCR) because of the high sensitivity and rapid turnaround time of the test. This paper describes methods for highly reproducible absolute viral load measurements using external standard curves generated with either ISAV recombinant plasmid DNA (pDNA) standards or transcribed RNA standards prepared by in vitro transcription with T7 RNA polymerase, and using a two tube real-time or quantitative (q)RT-PCR with SYBR® Green I chemistry and a single tube qRT-PCR with TaqMan® probe chemistry. When applied to virus samples of known virus titer for the highly pathogenic ISAV strain NBISA01 and the low pathogenic ISAV strain RPC/NB-04-085-1, both methods showed a 100-fold lower detectable titer for RPC/NB-04-085-1 but with a higher number of viral RNA molecules compared to NBISA01. Overall, the SYBR® Green I method overestimated copy numbers in samples having equivalent Ct values with the TaqMan® probe method. Taken together, the findings suggest that the TaqMan® probe method with the in vitro transcribed RNA standard curve is the preferred method for reliable and rapid quantitation of ISAV in samples.


title: A case–control study of pathogen and lifestyle risk factors for diarrhoea in dogs

text: Abstract Diarrhoea is a common and multi-factorial condition in dogs, the aetiology of which is often incompletely understood. A case–control study was carried out to compare the carriage of some common canine enteric pathogens (enteric coronavirus, parvovirus, distemper, endoparasites, Campylobacter and Salmonella spp.), as well as lifestyle factors such as vaccination history, diet and contact with other species, in dogs presenting at first opinion veterinary practices with and without diarrhoea. Multivariable conditional logistic regression showed that dogs in the study which scavenged or had had a recent change of diet (OR 3.5, p =0.002), had recently stayed in kennels (OR 9.5, p =0.01), or were fed a home-cooked diet (OR 4, p =0.002) were at a significantly greater risk of diarrhoea, whilst being female (OR 0.4, p =0.01), currently up to date with routine vaccinations (OR 0.4, p =0.05) and having contact with horse faeces (OR 0.4, p =0.06) were associated with a reduced risk. None of the pathogens tested for was a significant factor in the final multivariable model suggesting that in this predominantly vaccinated population, diarrhoea may be more associated with lifestyle risk factors than specific pathogens.


title: ACAM2000 clonal Vero cell culture vaccinia virus (New York City Board of Health strain) – a second-generation smallpox vaccine for biological defense

text: Summary The threat of smallpox as a biological weapon has spurred efforts to create stockpiles of vaccine for emergency preparedness. In lieu of preparing vaccine in animal skin (the original method), we cloned vaccinia virus (New York City Board of Health strain, Dryvax®) by plaque purification and amplified the clone in cell culture. The overarching goal was to produce a modern vaccine that was equivalent to the currently licensed Dryvax® in its preclinical and clinical properties, and could thus reliably protect humans against smallpox. A variety of clones were evaluated, and many were unacceptably virulent in animal models. One clonal virus (ACAM1000) was selected and produced at clinical grade in MRC-5 human diploid cells. ACAM1000 was comparable to Dryvax® in immunogenicity and protective activity but was less neurovirulent for mice and nonhuman primates. To meet requirements for large quantities of vaccine after the events of September 11th 2001, the ACAM1000 master virus seed was used to prepare vaccine (designated ACAM2000) at large scale in Vero cells under serum-free conditions. The genomes of ACAM1000 and ACAM2000 had identical nucleotide sequences, and the vaccines had comparable biological phenotypes. ACAM1000 and ACAM2000 were evaluated in three Phase 1 clinical trials. The vaccines produced major cutaneous reactions and evoked neutralizing antibody and cell-mediated immune responses in the vast majority of subjects and had a reactogenicity profile similar to that of Dryvax®.


title: Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots

text: Abstract Ethnopharmacological relevance . Scutellaria baicalensis Georgi (Labiatae) is a well-known traditional Chinese medicine to treat inflammation, cardiovascular diseases, respiratory and gastrointestinal infections, etc. The present study was to understand the metabolism of the root of Scutellaria baicalensis (a.k.a. Huangqin in Chinese) in the gastrointestinal tract and the correlation between the metabolites and their respective pharmacological activities. Materials and methods The water extract of the root of Scutellaria baicalensis (WESB) was incubated with simulated gastric and intestinal juices, and human fecal microflora for 24h at 37°C. The HPLC–DAD analysis was used to monitor the in vitro metabolic process and identify its metabolites by comparing their absorption spectrum and retention time with those of chemical references. The in vitro anticomplementary and antimicrobial activity was evaluated with hemolysis assay, agar disc-diffusion method and MIC value, respectively. Results Main constituents of WESB remain unchanged during the incubation with simulated gastric juice (pH=1.5) and intestinal juice (pH=6.8), whereas four flavones, baicalin, wogonoside, oroxyloside and norwogonoside were metabolized into their respective aglycons by human intestinal bacteria. All four metabolites were demonstrated to have higher anticomplementary and antimicrobial activity than those of WESB. The anticomplementary active metabolites were identified to be baicalein, oroxylin A and norwogonin, among them, norwogonin is the most active compound. Conclusion The presence of intestinal bacteria is demonstrated to play an important role in the gastrointestinal metabolism of WESB, and the pharmacological effects of Scutellaria baicalensis may be dependent on the intestinal bacteria metabolism.


Reliability and usefulness of a rapid IgM‐IgG antibody test for the diagnosis of SARS-CoV-2 infection: a preliminary report.


title: Availability of feces-free areas in rodent shoebox cages

text: The Guide for the Care and Use of Laboratory Animals (the Guide) recommends that terrestrial mammals be provided space free of urine and feces in which to rest. To evaluate the feasibility of meeting this recommendation, the author examined the availability of feces-free resting areas in standard rodent cages over time. Adult rodents (C57BL/6J mice and Wistar rats) were housed singly, in pairs or in trios in shoebox cages at densities that met the space recommendations of the Guide. As housing density increased, the availability of unsoiled resting space declined. For C57BL/6J mice housed singly, in pairs or in trios, most cages lacked unsoiled resting area within 3–6 days (depending on cage size), 2 days or 1 day, respectively. Similarly, for Wistar rats housed singly, in pairs or in trios, most cages lacked adequate unsoiled resting space within 3 days, 2 days or 1 day, respectively. Because most cages lacked adequate unsoiled resting space within 3 days of housing animals, the author concludes that standard cage change frequencies of once a week for adult C57BL/6J mice and twice a week for adult Wistar rats may be inadequate to provide unsoiled resting areas for rodents.