title: Can pioglitazone be potentially useful therapeutically in treating patients with covid-19?

text: Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPARγ agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.


title: Emerging Biomolecular Testing to Assess the Risk of Mortality from COVID-19 Infection

text: [Image: see text] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 and COVID-19) has produced an unprecedented global pandemic. Though the death rate from COVID-19 infection is ∼2%, many infected people recover at home. Among patients for whom COVID-19 is deadly are those with pre-existing comorbidities. Therefore, identification of populations at highest risk of COVID-19 mortality could significantly improve the capacity of healthcare providers to take early action and minimize the possibility of overwhelming care centers, which in turn would save many lives. Although several approaches have been used/developed (or are being developed/suggested) to diagnose COVID-19 infection, no approach is available/proposed for fast diagnosis of COVID-19 infections likely to be fatal. The central aim of this short perspective is to suggest a few possible nanobased technologies (i.e., protein corona sensor array and magnetic levitation) that could discriminate COVID-19-infected people while still in the early stages of infection who are at high risk of death. Such discrimination technologies would not only be useful in protecting health care centers from becoming overwhelmed but would also provide a powerful tool to better control possible future pandemics with a less social and economic burden.


Oncology clinical trials in the time of COVID-19: how a pandemic can revolutionize patients’ care


title: COVID-19 and Cancer: a Comprehensive Review

text: PURPOSE OF REVIEW: The outbreak of the novel coronavirus disease 2019 (COVID-19) has emerged to be the biggest global health threat worldwide, which has now infected over 1.7 million people and claimed more than 100,000 lives around the world. Under these unprecedented circumstances, there are no well-established guidelines for cancer patients. RECENT FINDINGS: The risk for serious disease and death in COVID-19 cases increases with advancing age and presence of comorbid health conditions. Since the emergence of the first case in Wuhan, China, in December 2019, tremendous research efforts have been underway to understand the mechanisms of infectivity and transmissibility of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a fatal virus responsible for abysmal survival outcomes. To minimize the mortality rate, it becomes prudent to identify symptoms promptly and employ treatments appropriately. Even though no cure has been established, multiple clinical trials are underway to determine the most optimal strategy. Managing cancer patients under these circumstances is rather challenging, given their vulnerable status and the aggressive nature of their underlying disease. SUMMARY: In this comprehensive review, we discuss the impact of COVID-19 on health and the immune system of those affected, reviewing the latest treatment approaches and ongoing clinical trials. Additionally, we discuss challenges faced while treating cancer patients and propose potential approaches to manage this vulnerable population during this pandemic.


title: Structural genomics of the SARS coronavirus: cloning, expression, crystallization and preliminary crystallographic study of the Nsp9 protein

text: The aetiologic agent of the recent epidemics of Severe Acute Respiratory Syndrome (SARS) is a positive‐stranded RNA virus (SARS‐CoV) belonging to the Coronaviridae family and its genome differs substantially from those of other known coronaviruses. SARS‐CoV is transmissible mainly by the respiratory route and to date there is no vaccine and no prophylactic or therapeutic treatments against this agent. A SARS‐CoV whole‐genome approach has been developed aimed at determining the crystal structure of all of its proteins or domains. These studies are expected to greatly facilitate drug design. The genomes of coronaviruses are between 27 and 31.5 kbp in length, the largest of the known RNA viruses, and encode 20–30 mature proteins. The functions of many of these polypeptides, including the Nsp9–Nsp10 replicase‐cleavage products, are still unknown. Here, the cloning, Escherichia coli expression, purification and crystallization of the SARS‐CoV Nsp9 protein, the first SARS‐CoV protein to be crystallized, are reported. Nsp9 crystals diffract to 2.8 Å resolution and belong to space group P6(1/5)22, with unit‐cell parameters a = b = 89.7, c = 136.7 Å. With two molecules in the asymmetric unit, the solvent content is 60% (V (M) = 3.1 Å(3) Da(−1)).


title: Risk of Bacterial Coinfections in Febrile Infants 60 Days Old and Younger with Documented Viral Infections

text: Objective To determine the risk of serious bacterial infections (SBIs) in young febrile infants with and without viral infections. Study design Planned secondary analyses of a prospective observational study of febrile infants 60 days of age or younger evaluated at 1 of 26 emergency departments who did not have clinical sepsis or an identifiable site of bacterial infection. We compared patient demographics, clinical, and laboratory findings, and prevalence of SBIs between virus-positive and virus-negative infants. Results Of the 4778 enrolled infants, 2945 (61.6%) had viral testing performed, of whom 1200 (48.1%) were virus positive; 44 of the 1200 had SBIs (3.7%; 95% CI, 2.7%-4.9%). Of the 1745 virus-negative infants, 222 had SBIs (12.7%; 95% CI, 11.2%-14.4%). Rates of specific SBIs in the virus-positive group vs the virus-negative group were: UTIs (33 of 1200 [2.8%; 95% CI, 1.9%-3.8%] vs 186 of 1745 [10.7%; 95% CI, 9.2%-12.2%]) and bacteremia (9 of 1199 [0.8%; 95% CI, 0.3%-1.4%] vs 50 of 1743 [2.9%; 95% CI, 2.1%-3.8%]). The rate of bacterial meningitis tended to be lower in the virus-positive group (0.4%) than in the viral-negative group (0.8%); the difference was not statistically significant. Negative viral status (aOR, 3.2; 95% CI, 2.3-4.6), was significantly associated with SBI in multivariable analysis. Conclusions Febrile infants ≤60 days of age with viral infections are at significantly lower, but non-negligible risk for SBIs, including bacteremia and bacterial meningitis.


title: Loop‐mediated isothermal amplification method for detection of human papillomavirus type 6, 11, 16, and 18

text: A new method was developed for detection of human papillomavirus (HPV) by loop‐mediated isothermal amplification (LAMP), which was compared with the polymerase chain reaction (PCR), and real‐time PCR for specificity and sensitivity. All initial validation studies with the control DNA proved to be type‐specific. In order to evaluate the reliability of HPV type‐specific LAMP detecting HPV DNA from clinical samples, tissue specimens were obtained from 27 patients with external genital polypoid lesions. The histologic diagnoses included condyloma acuminatum (n = 21), bowenoid papulosis (n = 2), seborrheic keratosis (n = 2), epidermolytic acanthoma (n = 1), and hairy nymphae (n = 1). HPV‐6 DNA and HPV‐11 DNA were detected in 18 and 3 of 21 condylomata acuminata, respectively, and there was no simultaneous infection. HPV‐16 DNA was detected in one of two bowenoid papuloses. HPV DNA was not detected in the seborrheic keratoses, epidermolytic acanthoma, and hairy nymphae. These results correlated perfectly with those from real‐time PCR analysis. Most positive samples contained high copy numbers of HPV DNA. HPV‐11 DNA was detected in one case that could not be detected by PCR. The average reaction time was about 59 min. There was a linear correlation between the genome quantity and reaction time to reach the threshold. The LAMP method has an additional advantage as a quantitative method, and is superior in terms of sensitivity, specificity, rapidity, and simplicity, and can potentially be a valuable tool for the detection of HPV DNA. J. Med. Virol. 79:605–615, 2007. © 2007 Wiley‐Liss, Inc.


Canadian Geriatrics in the Time of COVID‐19


title: Latent organizing for responding to emergencies: foundations for research

text: Time and again, many organizations and their staff members must respond to unexpected catastrophes like hurricanes (e.g., Katrina), virus pandemics (e.g., COVID-19), or other major emergencies. As a result, some organizations allow their employees to respond to external emergencies by engaging in response actions for a limited time, like in the case of emergency response teams. The latter teams consist of employees that act as emergency response officers who can respond to floods, train crashes, or other emergencies. Emergency response teams constitute an example of so-called latent organizing (LO) in the preparation for and response to any (unpredictable) future emergency. While latent organizing is ubiquitous in a societal and professional sense, it has hardly been studied in the organization design literature. In this paper, we develop a research agenda for studying LO. LO serves to prepare for and respond to emergencies, but otherwise remains largely dormant and inactive. When it is inactive, host organizations use the LO’s human and other resources for their own gainful purposes. Resources for LO are thus organized in a quasi-permanent fashion, one that is rather latent until activated by an emergency. We further develop the construct of latency to explore how effective LO can be designed and facilitated. In addition, we develop a research agenda for future work in this area.


title: Biological and phylogenetic characterization of a novel hemagglutination‐negative avian avulavirus 6 isolated from wild waterfowl in China

text: Up to now only nine whole genome sequences of avian avulavirus 6 (AAvV‐6) had been documented in the world since the first discovery of AAvV‐6 (AAvV‐6/duck/HongKong/18/199/77) at a domestic duck in 1977 from Hong Kong of China. Very limited information is known about the regularities of transmission, genetic and biological characteristics of AAvV‐6 because of the lower isolation rate and mild losses for poultry industry. To better further explore the relationships among above factors, an AAvV‐6 epidemiological surveillance of domestic poultry and wild birds in six provinces of China suspected of sites of inter‐species transmission and being intercontinental flyways during the year 2013–2017 was conducted. Therefore, 9,872 faecal samples from wild birds and 1,642 cloacal and tracheal swab samples from clinically healthy poultry of live bird market (LBM) were collected respectively. However, only one novel hemagglutination‐negative AAvV‐6 isolate (AAvV‐6/mallard/Hubei/2015) was isolated from a fresh faecal sample obtained from mallard at a wetland of Hubei province. Sequencing and phylogenetic analyses of this AAvV‐6 isolate (AAvV‐6/mallard/Hubei/2015) indicated that this isolate grouping to genotype I were epidemiological intercontinentally linked with viruses from the wild birds in Europe and America. Meanwhile, at least two genotypes (I and II) are existed within serotype AAvV‐6. In additional, this novel hemagglutination‐negative AAvV‐6 isolate in chicken embryos restored its hemagglutination when pre‐treated with trypsin. These findings, together with data from other AAvV‐6, suggest potential epidemiological intercontinental spreads among AAvV‐6 transmission by wild migratory birds, and reveal potential threats to wild birds and domestic poultry worldwide.


title: Characteristics and Clinical Outcomes of COVID‐19 Patients in an Underserved‐Inner City Population: A Single Tertiary Center Cohort

text: BACKGROUND: There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID‐19) especially those in underserved urban area with minority population in the United States. METHODS: This is a retrospective single center study for patients who were admitted with COVID‐19 infection. Data collection was from March 1 through April 24,2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. Chi‐square test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. RESULTS: A total of 242 inpatients were included with a mean age of 66 ±14.75 (±SD). 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death OR 1.056 [95% CI 1.023 to 1.090; p=0.001]. Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28‐65.60; p<0.0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74‐16.05; p<0.0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56 to 69.20; p<0.0001). Amongst biomarkers of disease severity, only baseline CRP levels (145±116 mg/L) were associated with mortality OR 1.008 [95% CI 1.003 to 1.012; p=0.002]. CONCLUSION: Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD were associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death. This article is protected by copyright. All rights reserved.


title: Corona-Krise: Was zeigt sich in der Herstellung und Bewältigung eines Ausnahmezustandes über die Möglichkeiten und Formen gesellschaftlicher Problembearbeitung?

text: Der Beitrag setzt sich mit der Frage auseinander, was den gesellschaftlichen Reaktionen auf die Ausbreitung des Coronavirus zu Grunde liegt. In einer sozialwissenschaftlichen Perspektive wird argumentiert, dass diese nicht zureichend als zwangsläufige politische Konsequenz aus Einsichten der medizinischen Virenforschung verstanden werden können, sondern auch als Folge einer fundamentalen kulturellen Verunsicherung in den Blick zu nehmen sind. Aufgezeigt wird zudem die nationalistische Rahmung der politischen Reaktionen. Abschließend wird darauf auf die Gefahr hingewiesen, dass das, was in einem deklarierten temporären Ausnahmezustand gesellschaftlich durchsetzbar ist, auch unter anderen Bedingungen aktualisiert werden könnte.


Eosinopenia and COVID-19 patients: So specific ?


title: Identification of an epitope of SARS-coronavirus nucleocapsid protein

text: The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is a major virion structural protein. In this study, two epitopes (N1 and N2) of the N protein of SARS-CoV were predicted by bioinformatics analysis. After immunization with two peptides, the peptides-specific antibodies were isolated from the immunized rabbits. The further experiments demonstrated that N1 peptide-induced polyclonal antibodies had a high affinity to bind to E. coli expressed N protein of SARS-CoV. Furthermore, it was confirmed that N1 peptide-specific IgG antibodies were detectable in the sera of severe acute respiratory syndrome (SARS) patients. The results indicated that an epitope of the N protein has been identified and N protein specific Abs were produced by peptide immunization, which will be useful for the study of SARS-CoV.


title: Sequence analysis of the porcine transmissible gastroenteritis coronavirus nucleocapsid protein gene

text: Abstract The 3′ end of the 20-kb genome of the Purdue strain of porcine transmissible gastroenteritis coronavirus (TGEV) was copied into eDNA after priming with oligo(dT) and the double-stranded product was cloned into the PstI site of the pUC9 vector. One clone of 2.0-kb contained part of the poly(A) tail and was sequenced in its entirety using the chemical method of Maxam and Gilbert. Another clone of 0.7 kb also contained part of the poly(A) tail and was sequenced in part to confirm the primary structure of the most 3′ end of the genome. Two potential, nonoverlapping genes were identified within the 3′-terminal 1663-base sequence from an examination of open reading frames. The first gene encodes a 382-amino acid protein of 43,426 mol wt, that is the apparent nucleocapsid protein on the basis of size, chemical properties, and amino acid sequence homology with other coronavirus nucleocapsid proteins. It is flanked on its 5′ side by at least part of the matrix protein gene. The second encodes a hypothetical 78-amino acid protein of 9101 mol wt that is hydrophobic at both ends. A 3′-proximal noncoding sequence of 276 bases was also determined and a conserved stretch of 9 nucleotides near the poly(A) tail was found to be common among TGEV, the mouse hepatitis coronavirus, and the avian infectious bronchitis coronavirus.


title: Endowing university spin-offs pre-formation: Entrepreneurial capabilities for scientist-entrepreneurs

text: Abstract University spin-offs are important mechanisms for creating and capturing value from scientific inventions. Academic scientists are uniquely positioned to shape such opportunities long before the university spin-off is founded. To better understand how science-based university spin-offs can be endowed for success, the pre-formation stage of 30 ventures co-founded over a 40 year period by a star-scientist-entrepreneur is analysed by matching his 363 co-invented US patents granted to 1476 co-authored publications and these 30 ventures. Employing the extended case method, including the analysis of extensive archival data, iterative interviews, and this unique, longitudinal, multi-level dataset, existing dynamic capabilities theory is confronted and extended with evidence as to how a star-scientist-entrepreneur senses and shapes and seizes opportunities to endow university spin-offs pre-formation. A process model is developed depicting four pre-formation entrepreneurial capabilities with which these science-based university spin-offs are endowed for success. Recommendations are made for scientist-entrepreneurs, investors, university leadership, and for innovation policymakers.


title: Specific detection of GII‐1 lineage of infectious bronchitis virus

text: Infectious bronchitis virus (IBV) is a worldwide prevalent RNA virus that causes highly contagious and economically devastating disease in chicken. The virus exists in many different genetic forms which made the disease control very difficult. The present study describes the development and validation of TaqMan probe‐based real‐time reverse transcription‐polymerase chain reaction (real‐time RT‐PCR) targeting the S1 coding region of S gene characteristic for the GII‐1 lineage (formerly the D1466‐like variant) of IBV. These strains are quite different from other European IBV belonging to different lineages of the GI genotype. The developed method was 30‐fold more sensitive than used so far for standard nested RT‐PCR with detection limit of 56 RNA copies per reaction. The specificity of the assay was also evaluated with a panel of different poultry pathogens. Repeatability and reproducibility of the method was very high with coefficients of variation lower than 4%. One hundred and twenty‐seven IBV‐positive samples were tested by this method and GII‐1 strains were detected in four of them (3·15%) which indicate a decrease in the GII‐1 IBV prevalence in Poland. The assay was proven to be a valuable tool for rapid diagnosis of GII‐1 lineage of IBV strains and moreover it enabled the monitoring of viral loads which can be used to assess disease progression. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports a TaqMan probe‐based real‐time reverse transcription‐polymerase chain reaction (real‐time RT‐PCR) for rapid and accurate identification of GII‐1 lineage (formerly D1466‐like variant) of infectious bronchitis virus (IBV). The assay revealed to be more sensitive than standard nested RT‐PCR assay, previously used for this purpose. The developed assay has been tested on numerous field samples and revealed 3·15% prevalence of this lineage of IBV in Polish chicken population. Moreover, this new assay enables the assessment of viral load measurement which might be useful for epidemiology and pathogenesis studies.


Feline coronavirus – that enigmatic little critter


Pharmacist's perspective on HCQ treatment of COVID‐19


title: Fine epitope mapping of monoclonal antibodies against hemagglutinin of a highly pathogenic H5N1 influenza virus using yeast surface display

text: Highly pathogenic H5N1 avian influenza viruses pose a debilitating pandemic threat. Thus, understanding mechanisms of antibody-mediated viral inhibition and neutralization escape is critical. Here, a robust yeast display system for fine epitope mapping of viral surface hemagglutinin (HA)-specific antibodies is demonstrated. The full-length H5 subtype HA (HA0) was expressed on the yeast surface in a correctly folded conformation, determined by binding of a panel of extensively characterized neutralizing human monoclonal antibodies (mAbs). These mAbs target conformationally-dependent epitopes of influenza A HA, which are highly conserved across H5 clades and group 1 serotypes. By separately displaying HA1 and HA2 subunits on yeast, domain mapping of two anti-H5 mAbs, NR2728 and H5-2A, localized their epitopes to HA1. These anti-H5 mAb epitopes were further fine mapped by using a library of yeast-displayed HA1 mutants and selecting for loss of binding without prior knowledge of potential contact residues. By overlaying key mutant residues that impacted binding onto a crystal structure of HA, the NR2728 mAb was found to interact with a fully surface-exposed contiguous patch of residues at the receptor binding site (RBS), giving insight into the mechanism underlying its potent inhibition of virus binding. The non-neutralizing H5-2A mAb was similarly mapped to a highly conserved H5 strain-specific but poorly accessible location on a loop at the trimer HA interface. These data further augment our toolchest for studying HA antigenicity, epitope diversity and accessibility in response to natural and experimental influenza infection and vaccines.


title: LearnCoil-VMF: computational evidence for coiled-coil-like motifs in many viral membrane-fusion proteins 1 1 Edited by F. E. Cohen

text: Abstract Crystallographic studies have shown that the coiled-coil motif occurs in several viral membrane-fusion proteins, including HIV-1 gp41 and influenza virus hemagglutinin. Here, the LearnCoil-VMF program was designed as a specialized program for identifying coiled-coil-like regions in viral membrane-fusion proteins. Based upon the use of LearnCoil-VMF, as well as other computational tools, we report detailed sequence analyses of coiled-coil-like regions in retrovirus, paramyxovirus and filovirus membrane-fusion proteins. Additionally, sequence analyses of these proteins outside their putative coiled-coil domains illustrate some structural differences between them. Complementing previous crystallographic studies, the coiled-coil-like regions detected by LearnCoil-VMF provide further evidence that the three-stranded coiled coil is a common motif found in many diverse viral membrane-fusion proteins. The abundance and structural conservation of this motif, even in the absence of sequence homology, suggests that it is critical for viral-cellular membrane fusion. The LearnCoil-VMF program is available at http://web.wi.mit.edu/kim


title: Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis

text: Abstract Background In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.


title: Concerns related to COVID‐19 pandemic among patients with inflammatory bowel disease and its influence on patient management

text: A novel coronavirus, currently identified as COVID-19, was recently defined as the cause of a cluster of patients with pneumonia of unknown origin that was initially reported from Wuhan, Hubei province, People's Republic of China.


title: A Novel Coronavirus from Patients with Pneumonia in China, 2019

text: In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)


title: Cell cycle perturbations induced by human herpesvirus 6 infection and their effect on virus replication

text: In this study, we demonstrate that infection of HSB-2 cells with human herpesvirus 6 (HHV-6) resulted in the accumulation of infected cells in the G2/M phase of the cell cycle. Analysis of various cell-cycle-regulatory proteins indicated that the levels of cyclins A2, B1, and E1 were increased in HHV-6-infected cells, but there was no difference in cyclin D1 levels between mock-infected and HHV-6-infected cells. Our data also showed that inducing G2/M phase arrest in cells infected by HHV-6 provided favorable conditions for viral replication.


title: Importance of timely management of patients in reducing fatality rate of coronavirus disease 2019

text: Abstract The outbreak of coronavirus disease 2019 (COVID-19) characterized with pneumonia, firstly occurred in Wuhan city, China, in December 2019 has so far spread in over 200 countries and territories in the world. One of the important goals in facing outbreaks of COVID-19 is to reduce the case fatality rate. We reported here that the fatality rate of COVID-19 in other provinces of mainland China was 0.82% (121/14708), significantly lower than 6.62% (4512/68128) in Hubei province (p<0.0001). The main reason for the lower fatality rate was likely due to the timely management of the patients in other provinces, highlighting the importance of timely management of patients in reducing the fatality rate of COVID-19.


title: Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus induced acute respiratory distress syndrome

text: We report a case of virus-induced acute respiratory distress syndrome (ARDS) treated with parenteral vitamin C in a patient testing positive for enterovirus/rhinovirus on viral screening. This report outlines the first use of high dose intravenous vitamin C as an interventional therapy for ARDS, resulting from enterovirus/rhinovirus respiratory infection. From very significant preclinical research performed at Virginia Commonwealth University with vitamin C and with the very positive results of a previously performed phase I safety trial infusing high dose vitamin C intravenously into patients with severe sepsis, we reasoned that infusing identical dosing to a patient with ARDS from viral infection would be therapeutic. We report here the case of a 20-year-old, previously healthy, female who contracted respiratory enterovirus/rhinovirus infection that led to acute lung injury and rapidly to ARDS. She contracted the infection in central Italy while on an 8-d spring break from college. During a return flight to the United States, she developed increasing dyspnea and hypoxemia that rapidly developed into acute lung injury that led to ARDS. When support with mechanical ventilation failed, extracorporeal membrane oxygenation (ECMO) was initiated. Twelve hours following ECMO initiation, high dose intravenous vitamin C was begun. The patient’s recovery was rapid. ECMO and mechanical ventilation were discontinued by day-7 and the patient recovered with no long-term ARDS sequelae. Infusing high dose intravenous vitamin C into this patient with virus-induced ARDS was associated with rapid resolution of lung injury with no evidence of post-ARDS fibroproliferative sequelae. Intravenous vitamin C as a treatment for ARDS may open a new era of therapy for ARDS from many causes.


Telehealth for fighting the novel coronavirus: review of activities on Diabetes and Osteoporosis management in outbreak


title: Isolation, social stress, low socioeconomic status and its relationship to immune response in Covid-19 pandemic context

text: The coronavirus disease 2019 (COVID-19) outbreak was first reported December 2019, in Wuhan, China, and has since spread worldwide. Social distancing or isolation measures were taken to mitigate the pandemic. Furthermore, stress and low socioeconomic status in humans confer increased vulnerability to morbidity and mortality, what can be biologically observed. This condition tends to remain during the Covid-19 pandemic. Social disruption stress (SDR) raises important questions regarding the functioning of the immune system, and the release of several stress hormones.A molecular pattern, conserved transcriptional response to adversity (CTRA), is thought to have evolved to defend against physical injury during periods of heightened risk. Chronic CTRA activation could leave an organism vulnerable to viral infections, leading to increased pro-inflammatory gene expression and a suppression of anti-viral gene expression. The activation of such transcriptional status is related to conditions of social stress through either hostile human contact, or increased predatory vulnerability due to separation from the social group and also low socioeconomic status. This review aims to point out questions for government officials, researchers and health professionals to better target their actions during a pandemic and encourage studies for a better understanding of these characteristics.


title: Differential modulations of two glyceraldehyde 3-phosphate dehydrogenase mRNAs in response to bacterial and viral challenges in a marine teleost Oplegnathus fasciatus (Perciformes)

text: Abstract Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) has been recognized as an invariant internal control for various gene expression studies due to its classical housekeeping role in the glycolytic metabolism. However recently, this enzyme has been proven to be a multifunctional protein involved in diverse non-glycolytic activities. In the present study, two paralogue isoforms of GAPDH mRNAs were characterized from a marine teleost species, rockbream (Oplegnathus fasciatus; Perciformes) and their transcriptional responses to bacterial and viral infections were examined. Rockbream GAPDH1 and GAPDH2 cDNAs encoded 333 and 335 amino acids, respectively, and the amino acid sequence identity between those two isoforms was 74%. Two isoform GAPDH mRNAs were detected ubiquitously in all of tissues examined, but their expression levels were quite variable among tissues. Based on the real-time RT-PCR analysis, the transcription of rbGAPDH1 was affected by neither bacterial (Escherichia coli, Edwardsiella tarda, Vibrio anguillarum or Streptococcus iniae) nor viral (rockbream iridovirus; RBIV) challenges. However on the contrary, the mRNA expression of rbGAPDH2 was significantly up-regulated in liver resulting from the bacterial infections (up to 25-fold), and in both liver (more than sixfold) and kidney (up to fivefold) from the viral infection. Results in the present study suggest that teleost GAPDH isoforms may also be potentially involved in immune modulations especially with respect to inflammatory responses, which is distinct from its classical glycolytic function.


title: Identification and complete genome characterization of human enterovirus 117 from a child with pneumonia in China

text: In this study, human enterovirus C117 (EV-C117) was detected in a 3-month-old boy diagnosed with pneumonia in China. A phylogenetic analysis showed that this strain was genetically closer to the Lithuanian strain than to the USA strain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04196-y) contains supplementary material, which is available to authorized users.


title: Baricitinib therapy in COVID-19: A pilot study on safety and clinical impact

text: • Baricitinib at 4 mg/day/orally was given to 12 patients with moderate COVID-19. • In baricitinib-treated patients no adverse events were recorded, after 2 weeks. • Clinical and respiratory parameters significantly improved at 2 weeks. • None of the baricitinib-treated patients required admission to ICU. • Proper control group was missing; this is required to demonstrate the efficacy.


title: Serotype and genetic diversity of human rhinovirus strains that circulated in Kenya in 2008

text: BACKGROUND: Human rhinoviruses (HRVs) are a well‐established cause of the common cold and recent studies indicated that they may be associated with severe acute respiratory illnesses (SARIs) like pneumonia, asthma, and bronchiolitis. Despite global studies on the genetic diversity of the virus, the serotype diversity of these viruses across diverse geographic regions in Kenya has not been characterized. OBJECTIVES: This study sought to characterize the serotype diversity of HRV strains that circulated in Kenya in 2008. METHODS: A total of 517 archived nasopharyngeal samples collected in a previous respiratory virus surveillance program across Kenya in 2008 were selected. Participants enrolled were outpatients who presented with influenza‐like (ILI) symptoms. Real‐time RT‐PCR was employed for preliminary HRV detection. HRV‐positive samples were amplified using RT‐PCR and thereafter the nucleotide sequences of the amplicons were determined followed by phylogenetic analysis. RESULTS: Twenty‐five percent of the samples tested positive for HRV. Phylogenetic analysis revealed that the Kenyan HRVs clustered into three main species comprising HRV‐A (54%), HRV‐B (12%), and HRV‐C (35%). Overall, 20 different serotypes were identified. Intrastrain sequence homology among the Kenyan strains ranged from 58% to 100% at the nucleotide level and 55% to 100% at the amino acid level. CONCLUSION: These results show that a wide range of HRV serotypes with different levels of nucleotide variation were present in Kenya. Furthermore, our data show that HRVs contributed substantially to influenza‐like illness in Kenya in 2008.


title: Fostering global primary care research: a capacity-building approach

text: The Alma Ata and Astana Declarations reaffirm the importance of high-quality primary healthcare (PHC), yet the capacity to undertake PHC research—a core element of high-quality PHC—in low-income and middle-income countries (LMIC) is limited. Our aim is to explore the current risks or barriers to primary care research capacity building, identify the ongoing tensions that need to be resolved and offer some solutions, focusing on emerging contexts. This paper arose from a workshop held at the 2019 North American Primary Care Research Group Annual Meeting addressing research capacity building in LMICs. Five case studies (three from Africa, one from South-East Asia and one from South America) illustrate tensions and solutions to strengthening PHC research around the world. Research must be conducted in local contexts and be responsive to the needs of patients, populations and practitioners in the community. The case studies exemplify that research capacity can be strengthened at the micro (practice), meso (institutional) and macro (national policy and international collaboration) levels. Clinicians may lack coverage to enable research time; however, practice-based research is precisely the most relevant for PHC. Increasing research capacity requires local skills, training, investment in infrastructure, and support of local academics and PHC service providers to select, host and manage locally needed research, as well as to disseminate findings to impact local practice and policy. Reliance on funding from high-income countries may limit projects of higher priority in LMIC, and ‘brain drain’ may reduce available research support; however, we provide recommendations on how to deal with these tensions.


title: Estimation of RAAS-Inhibitor effect on the COVID-19 outcome: A Meta-analysis

text: BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with ∼ 23 % reduced risk f death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.


title: Application of Universal Design for Learning (UDL) Principles to Surgical Education during the COVID-19 Pandemic: UDL for surgical education during COVID-19

text: During the COVID-19 pandemic in 2020, we have faced unprecedented challenges in the delivery of surgical education. At the time of writing, changes to the structure and nature of the surgical workforce are occurring rapidly, even daily. Surgical educators are utilizing remote learning solutions, including flipped classroom approaches, online educational materials, telemedicine, and simulations, to continue education for surgical residents despite cancelations of face-to-face instruction. Universal Design for Learning (UDL) provides a framework that can be used to situate such solutions within the broader view of strategic inclusive instructional design that aims to meet diverse learning needs. The principles of UDL can inform curricular and pedagogical changes in surgical education that may be employed during a time of social distancing, isolation, and quarantine. UDL involves planning flexibility into curricular design from the outset, recognizing that learners are varied in their learning preferences and capabilities, motivational characteristics, and environmental constraints. Viewing the design of remote learning opportunities through the UDL lens aims to remove barriers to learning during this pandemic by targeting three areas – expansion of the means that information is communicated, ways that learners are supported and motivated, and approaches to assessing learning through available distance learning technologies.


title: We were warned, so why couldn't we prevent it?

text: SARS and MERS gave us ample warning of the risk of new coronaviruses, but we failed to set up sufficient defences, reports Debora MacKenzie


title: Children’s Participation in a Virtual Epidemic in the Science Classroom: Making Connections to Natural Infectious Diseases

text: This study investigated students’ understanding of a virtual infectious disease in relation to their understanding of natural infectious diseases. Two sixth-grade classrooms of students between the ages of 10 and 12 (46 students) took part in a participatory simulation of a virtual infectious disease, which was integrated into their science curriculum. The results from our analyses reveal that students perceived the simulation as similar to a natural infectious disease and that the immersive components of the simulation afforded students the opportunity to discuss their understandings of natural disease and to compare them to their experiences with the virtual disease. We found that while the virtual disease capitalized on students’ knowledge of natural infectious disease through virtual symptoms, these symptoms may have led students to think of its transfer more as an observable or mechanical event rather than as a biological process. These findings provide helpful indicators to science educators and educational designers interested in creating and integrating online simulations within classroom environments to further students’ conceptual understanding.


title: Acute Necrotizing Encephalitis in Viral Respiratory Tract Infection: An Autopsy Case Report

text: Acute necrotizing encephalitis (ANE) is a rare complication of viral respiratory tract infections, with specific histological changes. The condition is most commonly described in the pediatric population, however, it can also develop in the elderly, with some genetic factors being described as contributory. Herein, we report the autopsy finding of a patient with a viral respiratory tract infection, complicated with ANE. The patient was a 77-year-old female with multiple comorbidities living in a social home. For the two months prior, she had been hospitalized with cerebral infarction, respiratory tract infection, and exacerbation of chronic cardiac failure and concomitant hypertension and type 2 diabetes. On gross examination, the brain was edematous, with ground-glass opacity meninges a focus of encephalomalacia in the right cerebral hemisphere and multiple petechial hemorrhages. Histology revealed diffuse foci of encephalitis, with large areas of neuronal necrosis (coagulative-like necrosis) around the blood vessels and a sharp border with the surrounding healthy parenchyma - ANE. The patients tested negative for coronavirus disease 2019 (COVID-19).


title: Molecular surveillance of canine distemper virus in diarrhoetic puppies in northeast China from May 2014 to April 2015

text: To trace the prevalence of canine distemper virus (CDV) in diarrhoetic dogs, a total of 201 stool samples were collected in the Heilongjiang province of northeastern China from May 2014 to April 2015. The 201 fecal samples were subjected to the detection of CDV by using RT-PCR targeting the partial N gene, phylogenetic analysis based on the complete H gene, and co-infection analysis. Results indicated that 24.88% (50/201) of the samples were positive for CDV. The fifty CDV samples exhibited an overall co-infection rate of 94% (47/50) with four enteric viruses (82%, 41/50) and five bacteria (72%, 36/50). The positivity rate of CDV exhibited differences among regions, seasons, ages and immunization status. Phylogenetic analysis of the complete H genes (n=6) revealed that the CDV strains identified in our study belonged to the Asia-1 group, and showed genetic diversities. These data provide evidence that there are a number of genetically diverse CDV Asia-1 strains circulating in diarrhoetic dogs in northeastern China; the CDV-affected animals exhibit the high co-infection with other enteric viruses and bacteria.


title: Visualizing Clinical Evidence: Citation Networks for the Incubation Periods of Respiratory Viral Infections

text: Simply by repetition, medical facts can become enshrined as truth even when there is little empirical evidence supporting them. We present an intuitive and clear visual design for tracking the citation history of a particular scientific fact over time. We apply this method to data from a previously published literature review on the incubation period of nine respiratory viral infections. The resulting citation networks reveal that the conventional wisdom about the incubation period for these diseases was based on a small fraction of available data and in one case, on no retrievable empirical evidence. Overall, 50% of all incubation period statements did not provide a source for their estimate and 65% of original sources for incubation period data were not incorporated into subsequent publications. More standardized and widely available methods for visualizing these histories of medical evidence are needed to ensure that conventional wisdom cannot stray too far from empirically supported knowledge.


COVID-19 travel restrictions and the International Health Regulations – call for an open debate on easing of travel restrictions


title: Genetic diversity and ecology of coronaviruses hosted by cave-dwelling bats in Gabon

text: Little research on coronaviruses has been conducted on wild animals in Africa. Here, we screened a wide range of wild animals collected in six provinces and five caves of Gabon between 2009 and 2015. We collected a total of 1867 animal samples (cave-dwelling bats, rodents, non-human primates and other wild animals). We explored the diversity of CoVs and determined the factors driving the infection of CoVs in wild animals. Based on a nested reverse transcription-polymerase chain reaction, only bats, belonging to the Hipposideros gigas (4/156), Hipposideros cf. ruber (13/262) and Miniopterus inflatus (1/249) species, were found infected with CoVs. We identified alphacoronaviruses in H. gigas and H. cf. ruber and betacoronaviruses in H. gigas. All Alphacoronavirus sequences grouped with Human coronavirus 229E (HCoV-229E). Ecological analyses revealed that CoV infection was significantly found in July and October in H. gigas and in October and November in H. cf ruber. The prevalence in the Faucon cave was significantly higher. Our findings suggest that insectivorous bats harbor potentially zoonotic CoVs; highlight a probable seasonality of the infection in cave-dwelling bats from the North-East of Gabon and pointed to an association between the disturbance of the bats’ habitat by human activities and CoV infection.


title: Standardized Preparation for Fecal Microbiota Transplantation in Pigs

text: The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.


title: Virus associés aux diarrhées aiguës. Actualités en 1991

text: Summary Viruses recovered in stools are either cultivable viruses (enteroviruses, adenoviruses excepted type 40 and 41), or “fastidious” non cultivable viruses (rotaviruses adenoviruses 40 and 41, Norwalk, calcivirus, astrovirus, SRSV and SRV). Non cultivable viruses have been associated with many cases of diarrhea. Norwalk, two strains of calicivirus and SRV/SRSV, appear to be capable of causing outbreak. Rotavirus, astrovirus and most fastidious adenoviruses are associated with endemic spread. Specific or catch-all methods are used for diagnosis. Among the latter, electron microscopy is the most commonly used when the virus is recognizable and present in sufficient quantities. Small spherical viruses in the range 20–35 nm present greater difficulties. Polyacrylamide gel electrophoresis gives interesting epidemiological results for rotavirus. Specific methods are latex agglutination and enzyme immunoassays essentially for rotavirus and adenoviruses (all types or only 40 and 41). False positive results are few with well-designed kits. False negative results are seen in atypical strains and antigenic variants. In an outbreak, it is essential to make electron microscopic examinations. In individual cases, if no electron microscope is available, it is possible to make the diagnosis of rotavirus — and perhaps adenovirus 40 and 41 with a commercial kit. However a small number of stools contain more than one virus and they may act in synergy. In contrast many asymptomatic children may carry viruses.


title: Human metapneumovirus and exacerbations of chronic obstructive pulmonary disease

text: Summary Objective Respiratory viruses are a common trigger for exacerbations of chronic obstructive pulmonary disease (COPD). Human metapneumovirus (hMPV) is a paramyxovirus associated with respiratory tract infections and wheezing. Our aim was to determine whether hMPV was associated with exacerbations of COPD. Methods The study was designed as an observational cohort study carried out in a 944-bed urban teaching hospital located in New Haven, Connecticut. Between December 2002 and May 2003, patients hospitalized due to an exacerbation of COPD were identified. Nasopharyngeal specimens obtained from these patients were tested for human metapneumovirus by RT–PCR and for respiratory syncytial virus, influenza A and B, parainfluenza-1, -2, and -3 and adenovirus by a cytospin-enhanced direct immunofluorescence assay and/or viral culture. Results Fifty individuals met enrollment criteria and hMPV was identified in 6 (12%), respiratory syncytial virus in 4 (8%), influenza A in 2 (4%) and parainfluenza type 3 in 1 (2%) patients. Both A and B hMPV genotypes were identified in patients hospitalized due to exacerbations of COPD. Conclusion hMPV was frequently identified in patients hospitalized due to an exacerbation of COPD. Further studies are necessary to determine the epidemiology and the impact of hMPV in COPD patients.


title: Leptospirosis vaccines

text: Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP) vaccines, lipopolysaccharide (LPS) vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.


title: Characterization and evolution of the coronavirus porcine epidemic diarrhoea virus HLJBY isolated in China

text: A strain of porcine epidemic diarrhoea virus (PEDV), namely HLJBY, was isolated in Heilongjiang province, China. To provide insight into the understanding of the phylogenetic and the current epidemiological status of PEDV, PEDV HLJBY was compared with CV777 and other PEDV strains deposited in the GenBank. The homology between the entire genomic nucleotide sequences of PEDV HLJBY and CV777 was 97.7%. The homology of M gene was the highest (99.0%). However, the homology of ORF3 gene was 97.7%, and protein of ORF3 was 90.1%. In addition, HLJBY showed the highest nucleotide identity (99.9%) with PEDV‐SX/China/2017 strain and lowest similarity (91.2%) to PEDV/Belgorod/dom/2008 strain. We analysed the changes in S gene and its protein of PEDV HLJBY with 65 historic PEDV strains. The highest nucleotide identity was 99.9% compared with PEDV‐SX/China/2017 strain, and the lowest nucleotide identity was 60.0% compared with PEDV/Belgorod/dom/2008 strain. The length of deduced amino acid sequences of S proteins varied from 1,372 to 1,390 amino acids (aa). Compared with most aa sequences of S proteins, HLJBY exhibited 5 aa deletions (position 55, 59–61, 144). Analysis and comparison of open reading frame 3 (ORF3) proteins between HLJBY strain and other PEDV strains were also focused in this study. We revealed that the length of deduced amino acid sequences of ORF3 proteins was 80–224 aa among tested strains and the identity of HLJBY ORF3 amino acids with other PEDV strains was 71.4%–98.9%. ORF3 protein of both HLJBY strain and PEDV‐SX/China/2017 strain consists of 91 aa, with 133 aa deletions at their C' end in relation to the other tested PEDV strains. The phylogenetic tree based on different proteins or genes resulted in different phylogenetic groups. For pathogenicity evaluation of PEDV HLJBY strain, colostrum deprivation piglets were challenged with PEDV HLJBY, and PEDV reference strain CV777 as a control, the results showed that animals challenged with either of these PEDV strains developed diarrhoea, and histopathological examination of small intestines of challenged animals showed acute viral enteritis with villous atrophy in either PEDV HLJBY‐P10 or PEDV CV777‐P8 inoculated piglets.


title: The public health and clinical significance of Giardia and Cryptosporidium in domestic animals

text: Abstract Giardia and Cryptosporidium are common enteric parasites of domestic animals, particularly dogs, cats and livestock. Their occurrence is of potential significance from both clinical and public health perspectives yet, until recently, confusion over the taxonomy of these organisms prevented a clear understanding of the epidemiology of infections with both Giardia and Cryptosporidium. The recent application of molecular epidemiological tools has helped to resolve taxonomic issues, allowing cycles of transmission to be determined. In addition, advances have been made in elucidating mechanisms associated with pathogenesis, whereas only limited progress has been achieved in the areas of chemotherapy and prophylaxis.


title: Comparison of the Indicators of Psychological Stress in the Population of Hubei Province and Non-Endemic Provinces in China During Two Weeks During the Coronavirus Disease 2019 (COVID-19) Outbreak in February 2020

text: BACKGROUND: During February 2020, the coronavirus disease 2019 (COVID-19) epidemic in Hubei Province, China, was at its height, requiring isolation of the population. This study aimed to compare the emotional state, somatic responses, sleep quality, and behavior of people in Hubei Province with non-endemic provinces in China during two weeks in February 2020. MATERIAL/METHODS: Questionnaires were completed by 939 individuals (357 men; 582 women), including 33 from Hubei and 906 from non-endemic provinces. The Stress Response Questionnaire (SRQ) determined the emotional state, somatic responses, and behavior. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the duration of sleep and sleep quality. RESULTS: There were 939 study participants, aged 18–24 years (35.89%) and 25–39 years (35.57%); 65.92% were university students. During a two week period in February 2020, the emotional state and behavior of participants in Hubei improved, but the quality of sleep did not. Health workers and business people became increasingly anxious, but other professionals became less anxious. The data showed that most people in Hubei Province developed a more positive attitude regarding their risk of infection and the chances of surviving the COVID-19 epidemic. CONCLUSIONS: During a two-week period, front-line health workers and people in Hubei Province became less anxious about the COVID-19 epidemic, but sleep quality did not improve. Despite public awareness, levels of anxiety exist that affect the quality of life during epidemics, including periods of population quarantine. Therefore, health education should be combined with psychological counseling for vulnerable individuals.


title: Controlling nosocomial infection based on structure of hospital social networks

text: Abstract Nosocomial infection (i.e. infection in healthcare facilities) raises a serious public health problem, as implied by the existence of pathogens characteristic to healthcare facilities such as methicillin-resistant Staphylococcus aureus and hospital-mediated outbreaks of influenza and severe acute respiratory syndrome. For general communities, epidemic modeling based on social networks is being recognized as a useful tool. However, disease propagation may occur in a healthcare facility in a manner different from that in a urban community setting due to different network architecture. We simulate stochastic susceptible-infected-recovered dynamics on social networks, which are based on observations in a hospital in Tokyo, to explore effective containment strategies against nosocomial infection. The observed social networks in the hospital have hierarchical and modular structure in which dense substructure such as departments, wards, and rooms, are globally but only loosely connected, and do not reveal extremely right-skewed distributions of the number of contacts per individual. We show that healthcare workers, particularly medical doctors, are main vectors (i.e. transmitters) of diseases on these networks. Intervention methods that restrict interaction between medical doctors and their visits to different wards shrink the final epidemic size more than intervention methods that directly protect patients, such as isolating patients in single rooms. By the same token, vaccinating doctors with priority rather than patients or nurses is more effective. Finally, vaccinating individuals with large betweenness centrality (frequency of mediating connection between pairs of individuals along the shortest paths) is superior to vaccinating ones with large connectedness to others or randomly chosen individuals, which was suggested by previous model studies.


title: Identification of Residues of SARS-CoV nsp1 That Differentially Affect Inhibition of Gene Expression and Antiviral Signaling

text: An epidemic of Severe Acute Respiratory Syndrome (SARS) led to the identification of an associated coronavirus, SARS-CoV. This virus evades the host innate immune response in part through the expression of its non-structural protein (nsp) 1, which inhibits both host gene expression and virus- and interferon (IFN)-dependent signaling. Thus, nsp1 is a promising target for drugs, as inhibition of nsp1 would make SARS-CoV more susceptible to the host antiviral defenses. To gain a better understanding of nsp1 mode of action, we generated and analyzed 38 mutants of the SARS-CoV nsp1, targeting 62 solvent exposed residues out of the 180 amino acid protein. From this work, we identified six classes of mutants that abolished, attenuated or increased nsp1 inhibition of host gene expression and/or antiviral signaling. Each class of mutants clustered on SARS-CoV nsp1 surface and suggested nsp1 interacts with distinct host factors to exert its inhibitory activities. Identification of the nsp1 residues critical for its activities and the pathways involved in these activities should help in the design of drugs targeting nsp1. Significantly, several point mutants increased the inhibitory activity of nsp1, suggesting that coronaviruses could evolve a greater ability to evade the host response through mutations of such residues.


title: Oscillation, cooperativity, and intermediates in the self-repressing gene

text: Abstract Biological oscillators are vital to living organisms, which use them as clocks for time-sensitive processes. However, much is unknown about mechanisms which can give rise to coherent oscillatory behavior, with few exceptions (e.g., explicitly delayed self-repressors and simple models of specific organisms’ circadian clocks). We present what may be the simplest possible reliable gene network oscillator, a self-repressing gene. We show that binding cooperativity, which has not been considered in detail in this context, can combine with small numbers of intermediate steps to create coherent oscillation. We also note that noise blurs the line between oscillatory and non-oscillatory behavior.


title: An assessment of the emergency response among health workers involved in the 2010 cholera outbreak in northern Nigeria

text: Summary Background The 2010 cholera outbreak in northern Nigeria affected over 40,000 people, with a case fatality rate (CFR) of ≥3.75%. We assessed the emergency response of health care workers (HCWs) involved in case management. Method This was a cross-sectional study with data collected through a self-administered questionnaire. Data entry and analysis were performed using Epi info software. Results A total of 56 HCWs were interviewed. The mean age was 31 years (SD±8.16 years). The majority of the HCWs (80%; n =45) were aged 18–39 years. Most were community health extension workers (60%), and 3.6% (n =2) were medical doctors. Many of the HCWs had less than 2 years of work experience (42%). Additionally, 82% of the respondents had <1 week of cholera emergency response training, and 50% of the HCWs managed >20 suspected cases of cholera per day. Although 78% of HCWs reported the practice of universal safety precautions, 32% (n =18) knew HCWs who developed symptoms of cholera during the epidemic, most of which was believed to be hospital acquired (78%). We also found that 77% (n =43) of HCWs had no access to the required emergency response supplies. Conclusion Inadequate training, a lack of qualified HCWs and a limited supply of emergency response kits were reported. Therefore, the government and stakeholders should address the gaps noted to adequately control and prevent future epidemics.


title: A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases

text: We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation. Expression of the altered p.(Met1141Lys) variant in a PLCγ2-knockout DT40 cell line showed clearly enhanced BCR-triggered influx of external calcium when compared to control-transfected cells. Our results further expand the molecular basis of pediatric CVID and phenotypic spectrum of PLCγ2-related defects. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10875-019-00731-3) contains supplementary material, which is available to authorized users.


title: The CD200–CD200R1 Inhibitory Signaling Pathway: Immune Regulation and Host–Pathogen Interactions

text: The CD200:CD200R1 inhibitory signaling pathway has been implicated in playing a prominent role in limiting inflammation in a wide range of inflammatory diseases. CD200R1 signaling inhibits the expression of proinflammatory molecules including tumor necrosis factor, interferons, and inducible nitric oxide synthase in response to selected stimuli. Unsurprisingly, due to the regulatory role that CD200R1 plays in multiple inflammatory pathways, an increasing number of parasitic, bacterial, and viral pathogens exploit this pathway to suppress host defenses. A complete understanding of the pathways regulated by CD200R1 signaling and the diverse mechanisms that pathogens have evolved to manipulate the CD200:CD200R1 pathway can help identify clinical situations where targeting this interaction can be of therapeutic benefit. In this review, we compare CD200R1 to other pathogen-targeted inhibitory receptors and highlight how this signaling pathway is utilized by a diverse number of pathogens and, therefore, may represent a novel targeting strategy for the treatment of infectious diseases.


Preprints: What is their role in medical journals?


title: Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response

text: Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3′ UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA.


title: New immune pathways from chronic post-viral lung disease

text: To better understand the immunopathogenesis of chronic inflammatory lung disease, we established a mouse model of disease that develops after respiratory viral infection. The disease that develops in this model is similar to chronic obstructive lung disease in humans. Using this model we have characterized two distinct phases in the chronic disease process. The first phase appears at three weeks after viral infection and depends on type I interferon-dependent expression and then subsequent activation of the high-affinity IgE receptor (FcεRI) on conventional lung dendritic cells, which in turn recruit IL-13-producing CD4(+) T cells to the lower airways. The second phase becomes maximal at seven weeks after infection and depends on invariant natural killer T (iNKT) cells and lung macrophages. Cellular cross-talk relies on interactions between the semi-invariant Vα14Jα18 T-cell receptor on lung iNKT cells and CD1d on macrophages as well as iNKT cell-derived IL-13 and IL-13 receptor on macrophages. These interactions drive macrophages to a pattern of alternative activation and overproduction of IL-13. This innate immune axis is also activated in patients with chronic obstructive lung disease, as evidenced by increased numbers of iNKT cells and IL-13-producing alternatively activated macrophages marked by chitinase 1 production. Together the findings identify two new immune pathways responsible for early and late phases of chronic inflammatory lung disease in experimental and clinical settings. These findings extend our understanding of the complex mechanisms that underlie chronic obstructive lung disease and provide useful targets for diagnosis and therapy of this common disorder.


Real-time RT-PCR detection of 12 respiratory viral infections in four triplex reactions


title: Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM

text: Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.


title: Glucose-Regulated Protein 78 Interacts with Zika Virus Envelope Protein and Contributes to a Productive Infection

text: Zika virus (ZIKV; Flaviviridae) is a mosquito-borne flavivirus shown to cause fetal abnormalities collectively known as congenital Zika syndrome and Guillain-Barré syndrome in recent outbreaks. Currently, there is no specific treatment or vaccine available, and more effort is needed to identify cellular factors in the viral life cycle. Here, we investigated interactors of ZIKV envelope (E) protein by combining protein pull-down with mass spectrometry. We found that E interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78). Although other flaviviruses are known to co-opt ER resident proteins, including GRP78, to enhance viral infectivity, the role ER proteins play during the ZIKV life cycle is yet to be elucidated. We showed that GRP78 levels increased during ZIKV infection and localised to sites coincident with ZIKV E staining. Depletion of GRP78 using specific siRNAs significantly reduced reporter-virus luciferase readings, viral protein synthesis, and viral titres. Additionally, GRP78 depletion reduced the ability of ZIKV to disrupt host cell translation and altered the localisation of viral replication factories, though there was no effect on viral RNA synthesis. In summary, we showed GRP78 is a vital host-factor during ZIKV infection, which may be involved in the coordination of viral replication factories.


title: The human Cas1 protein: A sialic acid-specific O-acetyltransferase?

text: Sialic acids are important sugars at the reducing end of glycoproteins and glycolipids. They are among many other functions involved in cell–cell interactions, host–pathogen recognition and the regulation of serum half-life of glycoproteins. An important modification of sialic acids is O-acetylation, which can alter or mask the biological properties of the parent sialic acid molecule. The nature of mammalian sialate-O-acetyltransferases (EC 2.3.1.45) involved in their biosynthesis is still unknown. We have identified the human CasD1 (capsule structure1 domain containing 1) gene as a candidate to encode the elusive enzyme. The human CasD1 gene encodes a protein with a serine–glycine–asparagine–histidine hydrolase domain and a hydrophobic transmembrane domain. Expression of the Cas1 protein tagged with enhanced green fluorescent protein in mammalian and insect cells directed the protein to the medial and trans-cisternae of the Golgi. Overexpression of the Cas1 protein in combination with α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (GD3 synthase) resulted in an up to 40% increased biosynthesis of 7-O-acetylated ganglioside GD3. By quantitative real-time polymerase chain reaction, we found up to 5-fold increase in CasD1 mRNA in tumor cells overexpressing O-Ac-GD3. CasD1-specific small interfering RNA reduced O-acetylation in tumor cells. These results suggest that the human Cas1 protein is directly involved in O-acetylation of α2-8-linked sialic acids.


title: Large-Scale Preparation of UV-Inactivated SARS Coronavirus Virions for Vaccine Antigen

text: In general, a whole virion serves as a simple vaccine antigen and often essential material for the analysis of immune responses against virus infection. However, to work with highly contagious pathogens, it is necessary to take precautions against laboratory-acquired infection. We have learned many lessons from the recent outbreak of severe acute respiratory syndrome (SARS). In order to develop an effective vaccine and diagnostic tools, we prepared UV-inactivated SARS coronavirus on a large scale under the strict Biosafety Level 3 (BSL3) regulation. Our protocol for large-scale preparation of UV-inactivated SARS-CoV including virus expansion, titration, inactivation, and ultracentrifugation is applicable to any newly emerging virus we might encounter in the future.


title: Differential host cell gene expression regulated by the porcine reproductive and respiratory syndrome virus GP4 and GP5 glycoproteins

text: Abstract The porcine reproductive and respiratory syndrome virus (PRRSV) GP4 and GP5 proteins are two membrane-associated viral glycoproteins that have been shown to induce neutralizing antibodies. In the present study, the host cell gene expression profiles altered by the GP4 and GP5 proteins were investigated by the use of DNA microarrays. Sublines of Marc-145 and HeLa cells were established by stable transfection with open reading frame (ORF)4 and ORF5 of PRRSV, respectively, and differential gene expressions were studied using microarray chips embedded with 1718 human-expressed sequence tags. The genes for protein degradation, protein synthesis and transport, and various other biochemical pathways were identified. No genes involved in the apoptosis pathway appeared to be regulated in GP5-expressing cells. The microarray data may provide insights into the specific cellular responses to the GP4 and GP5 proteins during PRRSV infection.


title: Coronaviruses Detected in Bats in Close Contact with Humans in Rwanda

text: Bats living in close contact with people in Rwanda were tested for evidence of infection with viruses of zoonotic potential. Mucosal swabs from 503 bats representing 17 species were sampled from 2010 to 2014 and screened by consensus PCR for 11 viral families. Samples were negative for all viral families except coronaviruses, which were detected in 27 bats belonging to eight species. Known coronaviruses detected included the betacorona viruses: Kenya bat coronaviruses, Eidolon bat coronavirus, and Bat coronavirus HKU9, as well as an alphacoronavirus, Chaerephon Bat coronavirus. Novel coronaviruses included two betacorona viruses clustering with SARS-CoV, a 2d coronavirus, and an alphacoronavirus.


title: CpG-ODNs induced changes in cytokine/chemokines genes expression associated with suppression of infectious bronchitis virus replication in chicken lungs

text: Abstract The process of virus replication in host cells is greatly influenced by the set of cytokines, chemokines and antiviral substances activated as a result of host–virus interaction. Alteration of cytokines profiles through manipulation of the innate immune system by innate immune stimulants may be helpful in inhibiting virus replication in otherwise permissive cells. The aim of present studies was to characterize innate immune responses capable of inhibiting infectious bronchitis virus (IBV) replication in chicken lungs after in ovo administration of CpG ODN. In our experiments, CpG ODN 2007 or PBS solution was injected on 18th embryonic day (ED) via the chorioallontoic route. CpG ODN and PBS inoculated embryos were challenged with virulent IBV on the 19th ED. Lung tissue samples from experimental chicks were analysed for cytokines/chemokines gene expression at 24h, 48h, and 72h, post infection. Our data showed significant differential up-regulation of IFN-γ, IL-8 (CXCLi2) and MIP-1β genes and suppression of IL-6 gene expression being associated with inhibition of IBV replication in lungs tissue retrieved from embryos pre-treated with CpG ODN. It is expected that understanding of the innate immune modulation of target tissues by the virus and innate immune stimulants will be helpful in identification of valuable targets for development of novel, safe, effective and economical control strategies against IBV infection in chickens.


title: Conséquences psychopathologiques du confinement

text: Abstract The psychological effects of isolation have already been described in the literature (polar expeditions, submarines, prison). Nevertheless, the scale of confinement implemented during the COVID-19 pandemic is unprecedented. In addition to reviewing the published studies, we need to anticipate the psychological problems that could arise during or at a distance from confinement. We have gone beyond the COVID-19 literature in order to examine the implications of the known consequences of confinement, like boredom, social isolation, stress, or sleep deprivation. Anxiety, post-traumatic stress disorder, depression, suicidal or addictive behaviours, domestic violence are described effects of confinement, but the mechanisms of emergence of these disorders and their interrelationships remain to be studied. For example, what are the mechanisms of emergence of post-traumatic stress disorders in the context of confinement? We also remind the reader of points of vigilance to be kept in mind with regard to eating disorders and hallucinations. Hallucinations are curiously ignored in the literature on confinement, whereas a vast literature links social isolation and hallucinations. As with domestic violence, we need to look for these symptoms in order to enable management. Due to the broad psychopathological consequences, we have to look for these various symptoms to manage them. We quickly summarize the diagnostic and therapeutic approaches already in place, such as telemedicine, which is undergoing rapid development during the COVID-19 crisis.


Nucleotide sequence of the bovine enteric coronavirus BECV F15 mRNA 5 and mRNA 6 unique regions.


title: Potentials of plant-based substance to inhabit and probable cure for the COVID-19

text: COVID-19 has been the most devastating pandemic in human history. Despite the highest scientific efforts and investments, a reliable and certified medication has yet to be developed regarding to immune or cure this virus. However, while synthetic medications are gaining the focus of attentions, it appears from a significant number of recent studies that plant-based substances could also be potential candidates for developing effective and secure remedies against this novel disease. Citing such recent works, this review primarily demonstrates the antiviral potentials of medicinal plants for inhibiting human coronaviruses. It also shows the importance of antiviral plants substances, particularly in the development of a broad spectrum medication for coronaviruses including SARS-CoV-2 responsible for COVID-19.


title: Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings

text: BACKGROUND: Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings. METHODS: Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy. RESULTS: In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001). CONCLUSIONS: Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting.


title: Complete Genome Sequence of a Recombinant Porcine Epidemic Diarrhea Virus Strain, CH/JXJA/2017, Isolated in Jiangxi, China, in 2017

text: The full-length genome sequence of a variant of porcine epidemic diarrhea virus (PEDV), that of strain CH/JXJA/2017, was highly homologous to CH/ZMDZY/11, a highly virulent Chinese PEDV strain. CH/JXJA/2017 had a distant relationship with the attenuated CV777 vaccine strain, but the insertion sites of the S1 gene were similar to those of the recombinant strain of CH/ZMDZY/11.


Mental Health of Scientists in the time of COVID-19


Letter in Response to Article in Journal of Infection: “High SARS-CoV-2 antibody prevalence among healthcare workers exposed to COVID-19 patients”


title: Pulmonary Delivery of Fenretinide: A Possible Adjuvant Treatment in COVID-19

text: At present, there is no vaccine or effective standard treatment for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (or coronavirus disease-19 (COVID-19)), which frequently leads to lethal pulmonary inflammatory responses. COVID-19 pathology is characterized by extreme inflammation and amplified immune response with activation of a cytokine storm. A subsequent progression to acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) can take place, which is often followed by death. The causes of these strong inflammatory responses in SARS-CoV-2 infection are still unknown. As uncontrolled pulmonary inflammation is likely the main cause of death in SARS-CoV-2 infection, anti-inflammatory therapeutic interventions are particularly important. Fenretinide N-(4-hydroxyphenyl) retinamide is a bioactive molecule characterized by poly-pharmacological properties and a low toxicity profile. Fenretinide is endowed with antitumor, anti-inflammatory, antiviral, and immunomodulating properties other than efficacy in obesity/diabetic pathologies. Its anti-inflammatory and antiviral activities, in particular, could likely have utility in multimodal therapies for the treatment of ALI/ARDS in COVID-19 patients. Moreover, fenretinide administration by pulmonary delivery systems could further increase its therapeutic value by carrying high drug concentrations to the lungs and triggering a rapid onset of activity. This is particularly important in SARS-CoV-2 infection, where only a narrow time window exists for therapeutic intervention.


title: Suicidal behaviour and suicide prevention in later life

text: Abstract Despite a general decline in late life suicide rates over the last 30 years, older people have the highest rates of suicide in most countries. In contrast, non-fatal suicidal behaviour declines with age and more closely resembles suicide than in younger age groups. There are difficulties in the detection and determination of pathological suicidal ideation in older people. Multiple factors increase suicide risk ranging from distal early and mid-life issues such as child abuse, parental death, substance misuse and traumatic life experiences to proximal precipitants in late life such as social isolation and health-related concerns. Clinical depression is the most frequently identified proximal mental health concern and in many cases is a first episode of major depression. Recent studies have identified changes on neuroimaging and neurocognitive factors that might distinguish suicidal from non-suicidal depression in older people. Strategies for suicide prevention need to be ‘whole of life’ and, as no single prevention strategy is likely to be successful alone, a multi-faceted, multi-layered approach is required. This should include optimal detection and management of depression and of high risk individuals as available evidence indicates that this can reduce suicidal behaviour. How best to improve the quality of depression management in primary and secondary care requires further research.


title: The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

text: There are few antiviral drugs for treating influenza, and the emergence of antiviral resistance has further limited the available therapeutic options. Furthermore, antivirals are not invariably effective in severe influenza, such as that caused by H5N1 viruses. Thus, there is an urgent need to develop alternative therapeutic strategies. Here, we show that human Vγ9Vδ2 T cells expanded by the aminobisphosphonate pamidronate (PAM) kill influenza virus–infected cells and inhibit viral replication in vitro. In Rag2(−/−)γc(−/−) immunodeficient mice reconstituted with human peripheral mononuclear cells (huPBMCs), PAM reduces disease severity and mortality caused by human seasonal H1N1 and avian H5N1 influenza virus, and controls the lung inflammation and viral replication. PAM has no such effects in influenza virus–infected Rag2(−/−)γc(−/−) mice reconstituted with Vγ9Vδ2 T cell–depleted huPBMCs. Our study provides proof-of-concept of a novel therapeutic strategy for treating influenza by targeting the host rather than the virus, thereby reducing the opportunity for the emergence of drug-resistant viruses. As PAM has been commonly used to treat osteoporosis and Paget’s disease, this new application of an old drug potentially offers a safe and readily available option for treating influenza.


title: Do policy burdens induce excessive managerial perks? Evidence from China's stated-owned enterprises()

text: This paper explores the effect of policy burdens of China's state-owned enterprises (SOEs) on senior executives' excessive perks. The empirical analysis demonstrates that SOE policy burdens are significantly and positively correlated with senior executives' excessive perks, indicating that SOE policy burdens increase agency cost. The results hold after controlling for potential endogeneity. Moreover, we find the following evidences. Strategic policy burdens of SOEs have a significantly greater impact on their senior executives' excessive perks, compared with social policy burdens. The positive impact of SOE policy burdens on excessive perks is significantly weaker in east China due to the higher degree of marketization. The central government's stricter supervision can also alleviate the positive correlation between policy burdens of centrally administered SOEs and senior executives' excessive perks.


title: Autoradiographic detection of IgG and viral antigens

text: Abstract Autoradiographic methods can be used as an alternative to indirect immunofluorescence to detect viral antigen expression or the presence of IgG in tissue sections. Iodinated protein A isolated from Staphylococcus aureus detects an influx of IgG into the central nervous system of mice inoculated with the coronavirus SD. Antispecies antibody that has been iodinated detects coronavirus antigen expression for 24 days post-inoculation while it is only detectable for 10 days by immunofluorescence. A direct comparison of indirect fluorescence and autoradiographic methods indicates that the autoradiographic techniques are considerably more sensitive. This increased sensitivity is sufficient to permit the detection of viral antigen in formalin fixed paraffin embedded tissue sections.


title: Earth Day: 50 Years of Continuity and Change in Environmentalism

text: In April 1970, the first Earth Day engaged millions of people in thousands of events around the US. Those events reflected the emergence of a new form of environmentalism. Many of the themes present 50 years ago persist, but in the US environmental issues have become more politically polarized, and it is unclear whether such value conflicts will persist in the future.


title: Biological characteristics and propagation of human rhinovirus-C in differentiated sinus epithelial cells

text: Abstract Information about the basic biological properties of human rhinovirus-C (HRV-C) viruses is lacking due to difficulties with culturing these viruses. Our objective was to develop a cell culture system to grow HRV-C. Epithelial cells from human sinuses (HSEC) were differentiated at air–liquid interface (ALI). Differentiated cultures supported 1–2 logs growth of HRV-C15 as detected by quantitative RT-PCR. Two distinguishing features of HRVs are acid lability and optimal growth at 33–34 °C. We used this system to show that HRV-C15 is neutralized by low pH (4.5). In contrast to most HRV types, replication of HRV-C15 and HRV-C41 was similar at 34 and 37°C. The HSEC ALI provides a useful tool for quantitative studies of HRV-C replication. The ability of HRV-C to grow equally well at 34°C and 37°C may contribute to the propensity for HRV-C to cause lower airway illnesses in infants and children with asthma.


title: Integrated sample inactivation, amplification, and Cas13-based detection of SARS-CoV-2

text: The COVID-19 pandemic has highlighted that new diagnostic technologies are essential for controlling disease transmission. Here, we develop SHINE (SHERLOCK and HUDSON Integration to Navigate Epidemics), a sensitive and specific integrated diagnostic tool that can detect SARS-CoV-2 RNA from unextracted samples. We combine the steps of SHERLOCK into a single-step reaction and optimize HUDSON to accelerate viral inactivation in nasopharyngeal swabs and saliva. SHINE’s results can be visualized with an in-tube fluorescent readout — reducing contamination risk as amplification reaction tubes remain sealed — and interpreted by a companion smartphone application. We validate SHINE on 50 nasopharyngeal patient samples, demonstrating 90% sensitivity and 100% specificity compared to RT-PCR with a sample-to-answer time of 50 minutes. SHINE has the potential to be used outside of hospitals and clinical laboratories, greatly enhancing diagnostic capabilities.


title: Rats Sniff Off Toxic Air

text: Breathing air is a fundamental human need, yet its safety, e.g., when challenged by various harmful or lethal substances, is often not properly guarded. Currently, air toxicity is monitored only for single or limited number of known toxicants, thus failing to fully warn against possible hazardous air. Here, using a photoionization detector (PID) or GC-MS/FID we found that within minutes living rats emitted distinctive profiles of volatile organic compounds (VOCs) via breath when exposed to various airborne toxicants such as endotoxin, O3, ricin, and CO2. Compared to background indoor air, when exposed to ricin or endotoxin aerosols breath-borne VOC levels, especially that of carbon disulfide, were shown to decrease, while elevated levels were observed for O3 and CO2 exposures. Principal component analysis (PCA) revealed a clear contrast in breath-borne VOCs profiles of rats among different toxicant exposures. MicroRNA regulations such as miR-33, miR-146a and miR-155 from rats’ blood samples also suggested varying mechanisms used by the rats in combating different air toxicant challenges. By integrating living rats, breath sampling, and VOC online detection, we pioneered a system that can real-time monitor air toxicity without the need of detecting specific species. Importantly, rats were shown to be able to sniff off toxic air. Abstract Graphic


title: Identification of potential molecules against COVID-19 main protease through structure-guided virtual screening approach

text: The pandemic caused by novel coronavirus disease 2019 (COVID-19) infecting millions of populations worldwide and counting, has demanded quick and potential therapeutic strategies. Current approved drugs or molecules under clinical trials can be a good pool for repurposing through in-silico techniques to quickly identify promising drug candidates. The structural information of recently released crystal structures of main protease (M(pro)) in APO and complex with inhibitors, N3, and 13b molecules was utilized to explore the binding site architecture through Molecular dynamics (MD) simulations. The stable state of M(pro) was used to conduct extensive virtual screening of the aforementioned drug pool. Considering the recent success of HIV protease molecules, we also used anti-protease molecules for drug repurposing purposes. The identified top hits were further evaluated through MD simulations followed by the binding free energy calculations using MM-GBSA. Interestingly, in our screening, several promising drugs stand out as potential inhibitors of M(pro). However, based on control (N3 and 13b), we have identified six potential molecules, Leupeptin Hemisulphate, Pepstatin A, Nelfinavir, Birinapant, Lypression and Octreotide which have shown the reasonably significant MM-GBSA score. Further insight shows that the molecules form stable interactions with hot-spot residues, that are mainly conserved and can be targeted for structure- and pharmacophore-based designing. The pharmacokinetic annotations and therapeutic importance have suggested that these molecules possess drug-like properties and pave their way for in-vitro studies. Communicated by Ramaswamy H. Sarma