title: Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study

text: BACKGROUND: The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS: For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40â162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS: We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15â000-41â000 contacts would be newly quarantined each day. INTERPRETATION: Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING: Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.


Hypertension and coronavirus disease 2019 mortality


Caring for patients with venous insufficiency during the COVID-19 pandemic at a tertiary care center


title: A Mouse Model of SARS-CoV-2 Infection and Pathogenesis

text: Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.


COVID-19 and venous thromboembolism: current insights and prophylactic strategies


title: Convalescent Plasma: Therapeutic Hope or Hopeless Strategy in the SARS-CoV-2 Pandemic

text: As the world faces the current SARS-CoV-2 pandemic, extensive efforts have been applied to identify effective therapeutic agents. Convalescent plasma collected from recovered patients has been a therapeutic modality employed for over a hundred years for various infectious pathogens. Specifically, it has been used in the treatment of many viral infections with varying degrees of clinical efficacy. As we consider the use of convalescent plasma in the battle against this new strain of coronavirus, it is prudent to review what is known from past experiences. Accordingly, the aim of this review is to examine in detail studies of convalescent plasma used during previous viral outbreaks and pandemics with particular focus on hemorrhagic fevers, influenza, and other coronaviruses. The concluding sections of this review address the potential use of convalescent plasma during the present-day SARS-CoV-2 pandemic, not only insofar as its clinical benefit but also the steps required to make convalescent plasma treatments readily available for an exponentially growing patient population. By the end, the authors hope to address the extent to which convalescent plasma represents a realistic therapeutic approach, or a distraction from other potentially useful treatments.


title: [Anosmia and ageusia as primary symptoms of COVID-19]

text: This case report describes a physician in the early 30ies with subjective anosmia and ageusia as the major presenting symptoms of COVID-19. Apart from a week of slightly runny nose when coming from cold to warm air, the only symptom was a sudden onset of persistent anosmia and ageusia. Two weeks after normalisation of the mild sino-nasal symptoms, the patient was tested positive for SARS-CoV-2, and anosmia was verified with Sniffin' Sticks tests. Hypogeusia was verified with taste screening and two validated taste tests. Olfactory and gustatory loss may be underestimated symptoms of COVID-19.


docid: qvoqyqxc

title: The ABC's of disaster management: Managing apheresis operations during the SARS-CoV-2 pandemic


title: Pandemic Uncertainty: Considerations for Nephrology Nurses

text: The COVID-19 pandemic is a situation of great magnitude that most of us have not experienced in our lifetime. Pandemics are widespread, affecting many geographical areas, and uncertainty is inherent given the rapidly changing situations. As nurses in dialysis providing a life-sustaining therapy, we are required to provide an essential service during pandemics and need to thrive in the uncertainty. This article offers points for consideration that can assist nephrology nurses in their approach to these uncertain times.


docid: sxwfnwak

title: Related molecular mechanisms of COVID-19, hypertension, and diabetes


COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction


Short-term outcomes in individuals aged 75 or older with severe coronavirus disease (COVID-19): First observations from an infectious diseases unit in Southern Italy


title: Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

text: Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for severe acute respiratory syndrome–coronavirus (SARS-CoV) and the new coronavirus (SARS-CoV-2) that is causing the serious coronavirus disease 2019 (COVID-19) epidemic. Here, we present cryo–electron microscopy structures of full-length human ACE2 in the presence of the neutral amino acid transporter B(0)AT1 with or without the receptor binding domain (RBD) of the surface spike glycoprotein (S protein) of SARS-CoV-2, both at an overall resolution of 2.9 angstroms, with a local resolution of 3.5 angstroms at the ACE2-RBD interface. The ACE2-B(0)AT1 complex is assembled as a dimer of heterodimers, with the collectrin-like domain of ACE2 mediating homodimerization. The RBD is recognized by the extracellular peptidase domain of ACE2 mainly through polar residues. These findings provide important insights into the molecular basis for coronavirus recognition and infection.


title: Effects of Housing and Colostrum Feeding on the Prevalence of Selected Infectious Organisms in Feces of Jersey Calves 1

text: Abstract Neonatal Jersey calves (n=96) were used to evaluate effects of housing (individual hutches or wooden pens in a barn) and colostrum feeding (calves were separated from the dam and fed 2 L of colostrum in nipple-bottles or allowed to nurse the dam for 3 d) on the prevalence of selected organisms in feces. Prevalence of Cryptosporidium and Eimeria were reduced, and prevalence of rotavirus tended to be reduced, when calves were housed in hutches. Prevalence of coronavirus was unaffected by treatment. Weekly prevalence of Giardia was increased when calves were left to nurse the dam for 3 d. Mean prevalence of Cryprosporidia (wk 1 to 4), Eimeria (wk 4 to 5), Giardia, rotavirus, and coronavirus (wk 1 to 5) were 34.7, 20.6, 27.1, 15.8, and 4.9%, respectively. Escherichia coli (K99 positive) were observed in 3 of 174 samples cultured. Methods of housing and colostrum feeding affected acquisition of enteropathogens in this study.


title: A Global Champion for Health—WHO’s Next?

text: In this month’s editorial, the PLOS Medicine Editors propose ideal qualities for the World Health Organization's next Director General, for whom the selection process is now underway.


title: Human Coronavirus EMC Does Not Require the SARS-Coronavirus Receptor and Maintains Broad Replicative Capability in Mammalian Cell Lines

text: A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from Rousettus, Rhinolophus, Pipistrellus, Myotis, and Carollia bats, representing four major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission.


title: COVID-19 serology at population scale: SARS-CoV-2-specific antibody responses in saliva

text: Non-invasive SARS-CoV-2 antibody testing is urgently needed to estimate the incidence and prevalence of SARS-CoV-2 infection at the general population level. Precise knowledge of population immunity could allow government bodies to make informed decisions about how and when to relax stay-at-home directives and to reopen the economy. We hypothesized that salivary antibodies to SARS-CoV-2 could serve as a non-invasive alternative to serological testing for widespread monitoring of SARS-CoV-2 infection throughout the population. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology and tested 167 saliva and 324 serum samples, including 134 and 118 negative saliva and serum samples, respectively, collected before the COVID-19 pandemic, and 33 saliva and 206 serum samples from participants with RT-PCR-confirmed SARS-CoV-2 infection. We evaluated the correlation of results obtained in saliva vs. serum and determined the sensitivity and specificity for each diagnostic media, stratified by antibody isotype, for detection of SARS-CoV-2 infection based on COVID-19 case designation for all specimens. Matched serum and saliva SARS-CoV-2 antigen-specific IgG responses were significantly correlated. Within the 10-plex SARS-CoV-2 panel, the salivary anti-nucleocapsid (N) protein IgG response resulted in the highest sensitivity for detecting prior SARS-CoV-2 infection (100% sensitivity at ≥10 days post-SARS-CoV-2 symptom onset). The salivary anti-receptor binding domain (RBD) IgG response resulted in 100% specificity. Among individuals with SARS-CoV-2 infection confirmed with RT-PCR, the temporal kinetics of IgG, IgA, and IgM in saliva were consistent with those observed in serum. SARS-CoV-2 appears to trigger a humoral immune response resulting in the almost simultaneous rise of IgG, IgM and IgA levels both in serum and in saliva, mirroring responses consistent with the stimulation of existing, cross-reactive B cells. SARS-CoV-2 antibody testing in saliva can play a critically important role in large-scale “sero”-surveillance to address key public health priorities and guide policy and decision-making for COVID-19.


title: Negotiating displacement, regaining community: The Harvard Language Center's response to the COVID‐19 crisis

text: The COVID‐19 crisis has fundamentally disrupted teaching and learning practices at many post‐secondary institutions with a highly residential population. The present article outlines the situation at Harvard University and details the steps taken by the Language Center to mitigate the effects of the transition to remote teaching and learning. These include changes in communication strategies, support mechanisms for faculty and students, and modifications to the Center's operational policies. The authors provide a number of concrete recommendations for academic support units in transitions of this type.


Up Front


title: SARS Surveillance during Emergency Public Health Response, United States, March–July 2003

text: In response to the emergence of severe acute respiratory syndrome (SARS), the United States established national surveillance using a sensitive case definition incorporating clinical, epidemiologic, and laboratory criteria. Of 1,460 unexplained respiratory illnesses reported by state and local health departments to the Centers for Disease Control and Prevention from March 17 to July 30, 2003, a total of 398 (27%) met clinical and epidemiologic SARS case criteria. Of these, 72 (18%) were probable cases with radiographic evidence of pneumonia. Eight (2%) were laboratory-confirmed SARS-coronavirus (SARS-CoV) infections, 206 (52%) were SARS-CoV negative, and 184 (46%) had undetermined SARS-CoV status because of missing convalescent-phase serum specimens. Thirty-one percent (124/398) of case-patients were hospitalized; none died. Travel was the most common epidemiologic link (329/398, 83%), and mainland China was the affected area most commonly visited. One case of possible household transmission was reported, and no laboratory-confirmed infections occurred among healthcare workers. Successes and limitations of this emergency surveillance can guide preparations for future outbreaks of SARS or respiratory diseases of unknown etiology.


title: T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections

text: Abstract A series of pyrazinecarboxamide derivatives T-705 (favipiravir), T-1105 and T-1106 were discovered to be candidate antiviral drugs. These compounds have demonstrated good activity in treating viral infections in laboratory animals caused by various RNA viruses, including influenza virus, arenaviruses, bunyaviruses, West Nile virus (WNV), yellow fever virus (YFV), and foot-and-mouth disease virus (FMDV). Treatment has in some cases been effective when initiated up to 5–7 days after virus infection, when the animals already showed signs of illness. Studies on the mechanism of action of T-705 have shown that this compound is converted to the ribofuranosyltriphosphate derivative by host enzymes, and this metabolite selectively inhibits the influenza viral RNA-dependent RNA polymerase without cytotoxicity to mammalian cells. Interestingly, these compounds do not inhibit host DNA and RNA synthesis and inosine 5′-monophosphate dehydrogenase (IMPDH) activity. From in vivo studies using several animal models, the pyrazinecarboxamide derivatives were found to be effective in protecting animals from death, reducing viral burden, and limiting disease manifestations, even when treatment was initiated after virus inoculation. Importantly, T-705 imparts its beneficial antiviral effects without significant toxicity to the host. Prompt development of these compounds is expected to provide effective countermeasures against pandemic influenza virus and several bioweapon threats, all of which are of great global public health concern given the current paucity of highly effective broad-spectrum drugs.


Corona – Covid -19 – Pandemic Are we in the Right Direction


Editorial, Authors Reply: Neurological Impact of Coronavirus Disease (COVID-19): Practical Considerations for the Neuroscience Community.


title: Enhancing Protein Backbone Binding—A Fruitful Concept for Combating Drug‐Resistant HIV

text: The evolution of drug resistance is one of the most fundamental problems in medicine. In HIV/AIDS, the rapid emergence of drug‐resistant HIV‐1 variants is a major obstacle to current treatments. HIV‐1 protease inhibitors are essential components of present antiretroviral therapies. However, with these protease inhibitors, resistance occurs through viral mutations that alter inhibitor binding, resulting in a loss of efficacy. This loss of potency has raised serious questions with regard to effective long‐term antiretroviral therapy for HIV/AIDS. In this context, our research has focused on designing inhibitors that form extensive hydrogen‐bonding interactions with the enzyme’s backbone in the active site. In doing so, we limit the protease’s ability to acquire drug resistance as the geometry of the catalytic site must be conserved to maintain functionality. In this Review, we examine the underlying principles of enzyme structure that support our backbone‐binding concept as an effective means to combat drug resistance and highlight their application in our recent work on antiviral HIV‐1 protease inhibitors.


docid: pzbcthjr

title: COVID-19 – Impact on DNR Orders in the Largest Cancer Center in Jordan

text: Abstract The COVID-19 pandemic requires healthcare teams to rethink how they can continue to provide high quality care for all patients, whether they are suffering from a COVID-19 infection or other diseases with clinical uncertainty. Although the number of cases of COVID-19 in Jordan remains relatively low compared to many other countries, our team introduced significant changes to team operations early, with the aim of protecting patients, families and healthcare staff from COVID-19 infections, while preparing to respond to the needs of patients suffering from severe COVID-19 infections. This paper describes the changes made to our ‘Do not resuscitate’ (DNR) policy for the duration of the pandemic.


title: Preparation and characterization of SARS in-house reference antiserum

text: A reference antiserum for SARS is in urgent need in the development of SARS vaccine and other serological test of SARS research. Convalescent serum was collected from clinical confirmed patient. ELISA, Western-blotting and neutralization assay detected specific antibody against SARS coronavirus. This antiserum was prepared as in-house reference antiserum, freeze-dried and sealed in ampoules. The potency of this reference antiserum is defined to be 52.7 U after extensive calibration. Further, collaborative studies for the evaluation of this serum are needed in order to satisfy the requirements for international reference antiserum.


title: Repurposing Existing Medications for Coronavirus Disease 2019: Protocol for a Rapid and Living Systematic Review

text: BACKGROUND: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. METHODS: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. DISCUSSION: The challenge posed by COVID-19 requires not just a rapid review of drugs that can be repurposed but also a sustained effort to integrate new evidence into a living systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2020 CRD42020175648


Malawi – Covid‐19, Promise to Protect Economy


docid: wvicjqdj

title: Identification and complete genome analysis of three novel paramyxoviruses, Tuhoko virus 1, 2 and 3, in fruit bats from China

text: Abstract Among 489 bats of 11 species in China, three novel paramyxoviruses [Tuhokovirus 1, 2 and 3 (ThkPV-1, ThkPV-2 and ThkPV-3)] were discovered in 15 Leschenault's rousettes. Phylogenetically, the three viruses are most closely related to Menangle and Tioman virus. Genome analysis showed that their 3'-leader sequences are unique by possessing GA instead of AG at the 5th and 6th positions. Unlike Menangle and Tioman virus, key amino acids for neuraminidase activity characteristic of rubulavirus attachment proteins are present. The genome of ThkPV-1 represents the largest rubulavirus genome. Unique features between the three viruses include perfect complementary 5'-trailer and 3'-leader sequence and a unique cysteine pair in attachment protein of ThkPV-1, G at +1 position in all predicted mRNA sequences of ThkPV-2, and amino acid substitutions in the conserved N-terminal motif of nucleocapsid of ThkPV-3. Analysis of phosphoprotein gene mRNA products confirmed mRNA editing. Antibodies to the viruses were detected in 48–60% of Leschenault's rousettes.


title: Alphacoronaviruses Detected in French Bats Are Phylogeographically Linked to Coronaviruses of European Bats

text: Bats are a reservoir for a diverse range of viruses, including coronaviruses (CoVs). To determine the presence of CoVs in French bats, fecal samples were collected between July and August of 2014 from four bat species in seven different locations around the city of Bourges in France. We present for the first time the presence of alpha-CoVs in French Pipistrellus pipistrellus bat species with an estimated prevalence of 4.2%. Based on the analysis of a fragment of the RNA-dependent RNA polymerase (RdRp) gene, phylogenetic analyses show that alpha-CoVs sequences detected in French bats are closely related to other European bat alpha-CoVs. Phylogeographic analyses of RdRp sequences show that several CoVs strains circulate in European bats: (i) old strains detected that have probably diverged a long time ago and are detected in different bat subspecies; (ii) strains detected in Myotis and Pipistrellus bat species that have more recently diverged. Our findings support previous observations describing the complexity of the detected CoVs in bats worldwide.


title: Digital transformation of everyday life – How COVID-19 pandemic transformed the basic education of the young generation and why information management research should care?

text: Children of today have been surrounded by digital technology since their birth. However, children of today are not equally equipped for their technology rich future: various kinds of digital divides still prevail in the society and affect the young generation and their digital futures. Schools and education of children should undergo an extensive digital transformation to be able to meet the needs of the young generation and their digitalized future. The COVID-19 pandemic has suddenly and abruptly forced schools and education indeed to engage in such a transformation. In this study we examine the digital transformation initiated by the COVID-19 pandemic in the basic education of the young generation, the variety of digital divides emerging and reinforced, and the possible barriers reported along the way. We argue that information management research should better acknowledge children, their digitalized everyday life and their basic education as significant areas of concern. We should understand them as well as allow them to shape the education we offer in the context of higher education, but we should also aim at influencing the basic education of the young generation – for the purpose of equipping them with important skills and competencies for their digital futures but also for the purpose of arousing their interest in this important field, maybe even as a career option.


title: The Pomegranate: Effects on Bacteria and Viruses That Influence Human Health

text: Pomegranates have been known for hundreds of years for their multiple health benefits, including antimicrobial activity. The recent surge in multidrug-resistant bacteria and the possibility of widespread global virus pandemics necessitate the need for additional preventative and therapeutic options to conventional drugs. Research indicates that pomegranates and their extracts may serve as natural alternatives due to their potency against a wide range of bacterial and viral pathogens. Nearly every part of the pomegranate plant has been tested for antimicrobial activities, including the fruit juice, peel, arils, flowers, and bark. Many studies have utilized pomegranate peel with success. There are various phytochemical compounds in pomegranate that have demonstrated antimicrobial activity, but most of the studies have found that ellagic acid and larger hydrolyzable tannins, such as punicalagin, have the highest activities. In some cases the combination of the pomegranate constituents offers the most benefit. The positive clinical results on pomegranate and suppression of oral bacteria are intriguing and worthy of further study. Much of the evidence for pomegranates' antibacterial and antiviral activities against foodborne pathogens and other infectious disease organisms comes from in vitro cell-based assays, necessitating further confirmation of in vivo efficacy through human clinical trials.


title: Sequence analysis of the 3′ end of the feline coronavirus FIPV 79-1146 genome: Comparison with the genome of porcine coronavirus TGEV reveals large insertions

text: Abstract The genetic information, carried on mRNA 6 of feline infectious peritonitis virus (FIPV) strain 79–1146, was determined by sequence analysis of cDNA clones derived from the 3′ end of the FIPV genome. Two ORFs were found, encoding polypeptides of 11 K (ORF-1) and 22K (ORF-2). The FIPV sequence was compared to the 3′ end sequence of transmissible gastroenteritis virus (TGEV). ORF-1 has a homologous counterpart (ORF-X3) in the TGEV genome; both ORFs are located at the same position relative to the nucleocapsid gene. However, as a result of an in-frame insertion or deletion, ORF-1 is 69 nucleotides larger than ORF-X3. A similar event has occurred immediately downstream of ORF1: a 624-nucleotide segment, containing the complete ORF-2, is absent in the TGEV sequence. Most sequence similarity (98.5%) was found in the 3′ noncoding sequences. ORF-X3 and ORF-1 are preceded by the sequence AAC-TAAAC, which is assumed to be the transcription-initiation signal in FIPV and TGEV (P. A. Kapke and D. A. Brian (1986) Virology 151, 41–49). By S1 nuclease analysis, the 5′ end of FIPV RNA 6 was mapped immediately upstream of this sequence. A 700-nucleotide TGEV-specific RNA was found by cross-hybridization with an FIPV 3′ end probe, suggesting that TGEV ORF-X3 is also carried on a separate mRNA. The differences at the 3′ ends of the FIPV and TGEV genomes maybe the result of RNA recombination events.


title: The use of infrared thermography as an early indicator of bovine respiratory disease complex in calves

text: Abstract Bovine respiratory disease (BRD) complex causes considerable distress to domestic livestock and economic hardship to the beef industry. Furthermore, the resulting extensive use of antimicrobial treatments is a growing concern from the perspective of facilitating antibiotic resistant microbes. The earlier detection of BRD would enable an earlier, more targeted treatment regime and earlier isolation of infected individuals. The objective of the present study was to investigate the use of non-invasive infrared thermography in the early detection of BRD in cattle. Studies were conducted on 133 head of weaned calves. Data demonstrated that infrared thermography was able to identify animals at early stages of illness, often several days to over one week before clinical signs were manifest. Data indicated that 4–6 days prior to the onset of clinical symptoms of BRD, greater positive and negative predictive values and test efficiency for infrared thermography (80%, 65% and 71%, respectively) compared to the industry standard practice of clinical scoring (70%, 45% and 55%, respectively).


title: Role of response gene to complement 32 in diseases

text: The role of response gene to complement (RGC)-32 as a cell cycle regulator has been attributed to its ability to activate cdc2 kinases and to induce S-phase entry and mitosis. However, recent studies revealed novel functions for RGC-32 in diverse processes such as cellular differentiation, inflammation, and fibrosis. Besides responding to C5b-9 stimulation, RGC-32 expression is also induced by growth factors, hormones, and cytokines. Transforming growth factor β activates RGC-32 through Smad and RhoA signaling, thus initiating smooth muscle cell differentiation. Accumulating evidence has drawn attention to the deregulated expression of RGC-32 in human malignancies, hyper-immunoglobulin E syndrome, and fibrosis. RCG-32 expression is up-regulated in cutaneous T cell lymphoma and colon, ovarian, and breast cancer, but down-regulated in invasive prostate cancer, multiple myeloma, and drug-resistant glioblastoma. A better understanding of the mechanism by which RGC-32 contributes to the pathogenesis of these diseases will provide new insights into its therapeutic potential. In this review we provide an overview of this field and discuss the most recent research on RGC-32.


title: Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

text: Abstract Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in infants and young children. There are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Immunomodulation mediated by a novel formulation consisting of the toll-like receptor 3 agonist poly(I:C), an innate defense regulator peptide and a polyphosphazene (P-I-P) was evaluated in the context of lethal infection with pneumonia virus of mice (PVM). Intranasal delivery of a single dose of P-I-P protected adult mice against PVM when given 24 h prior to challenge. These animals experienced minimal weight loss, no clinical disease, 100% survival, and reduced lung pathology. Similar clinical outcomes were observed in mice treated up to 3 days prior to infection. P-I-P pre-treatment induced early mRNA and protein expression of key chemokine and cytokine genes, reduced the recruitment of neutrophils and eosinophils, decreased virus titers in the lungs, and modulated the delayed exacerbated nature of PVM disease without any short-term side effects. On day 14 post-infection, P-I-P-treated mice were confirmed to be PVM-free. These results demonstrate the capacity of this formulation to prevent PVM and possibly other viral respiratory infections.


title: Susceptibility of Chickens to Porcine Deltacoronavirus Infection

text: Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus with worldwide distribution. PDCoV belongs to the Deltacoronavirus (DCoV) genus, which mainly includes avian coronaviruses (CoVs). PDCoV has the potential to infect human and chicken cells in vitro, and also has limited infectivity in calves. However, the origin of PDCoV in pigs, the host range, and cross-species infection of PDCoV still remain unclear. To determine whether PDCoV really has the ability to infect chickens in vivo, the three lines of chicken embryos and specific pathogen free (SPF) chickens were inoculated with PDCoV HNZK-02 strain to investigate PDCoV infection in the current study. Our results indicated that PDCoV can infect chicken embryos and could be continuously passaged on them. Furthermore, we observed that PDCoV-inoculated chickens showed mild diarrhea symptoms and low fecal viral RNA shedding. PDCoV RNA could also be detected in multiple organs (lung, kidney, jejunum, cecum, and rectum) and intestinal contents of PDCoV-inoculated chickens until 17 day post-inoculation by real-time quantitative PCR (qRT-PCR). A histology analysis indicated that PDCoV caused mild lesions in the lung, kidney, and intestinal tissues. These results prove the susceptibility of chickens to PDCoV infection, which might provide more insight about the cross-species transmission of PDCoV.


docid: vindspai

title: Distinguishing patients with laboratory-confirmed chikungunya from dengue and other acute febrile illnesses, Puerto Rico, 2012–2015

text: Chikungunya, a mosquito-borne viral, acute febrile illness (AFI) is associated with polyarthralgia and polyarthritis. Differentiation from other AFI is difficult due to the non-specific presentation and limited availability of diagnostics. This 3-year study identified independent clinical predictors by day post-illness onset (DPO) at presentation and age-group that distinguish chikungunya cases from two groups: other AFI and dengue. Specimens collected from participants with fever ≤7 days were tested for chikungunya, dengue viruses 1–4, and 20 other pathogens. Of 8,996 participants, 18.2% had chikungunya, and 10.8% had dengue. Chikungunya cases were more likely than other groups to be older, report a chronic condition, and present <3 DPO. Regardless of timing of presentation, significant positive predictors for chikungunya versus other AFI were: joint pain, muscle, bone or back pain, skin rash, and red conjunctiva; with dengue as the comparator, red swollen joints (arthritis), joint pain, skin rash, any bleeding, and irritability were predictors. Chikungunya cases were less likely than AFI and dengue to present with thrombocytopenia, signs of poor circulation, diarrhea, headache, and cough. Among participants presenting <3 DPO, predictors for chikungunya versus other AFI included: joint pain, skin rash, and muscle, bone or back pain, and absence of thrombocytopenia, poor circulation and respiratory or gastrointestinal symptoms; when the comparator was dengue, joint pain and arthritis, and absence of thrombocytopenia, leukopenia, and nausea were early predictors. Among all groups presenting 3–5 DPO, pruritic skin became a predictor for chikungunya, joint, muscle, bone or back pain were no longer predictive, while arthritis became predictive in all age-groups. Absence of thrombocytopenia was a significant predictor regardless of DPO or comparison group. This study identified robust clinical indicators such as joint pain, skin rash and absence of thrombocytopenia that can allow early identification of and accurate differentiation between patients with chikungunya and other common causes of AFI.


title: Need for Caution in the Diagnosis of Radiation Pneumonitis in the COVID-19 Pandemic

text: Abstract: Introduction Patients with cancer are at high-risk for mortality from coronavirus-disease 2019 (COVID-19). Radiation pneumonitis (RP) is a common toxicity of thoracic radiotherapy with overlapping clinical and imaging features with COVID-19, however, RP is treated with high-dose corticosteroids, which may exacerbate COVID-19-associated lung injury. We reviewed patients who presented with symptoms of RP during the intensification of a regional COVID-19 epidemic to report on their clinical course and COVID-19 testing results. Methods The clinical course and chest computed tomography (CT) imaging findings of consecutive patients who presented with symptoms of RP in March 2020 were reviewed. The first regional COVID-19 case was diagnosed on 3/1/2020. All patients underwent COVID-19 qualitative RNA testing. Results Four patients with clinical suspicion for RP were assessed. Three out of four patients tested positive for COVID-19. All patients presented with symptoms of cough and dyspnea. Two patients had a fever, of whom only one tested positive for COVID-19. Two patients started on an empiric high-dose corticosteroid taper for presumed RP, but both had clinical deterioration, and ultimately tested positive for COVID-19 and required hospitalization. Chest CT findings in patients suspected of RP, but ultimately diagnosed with COVID-19 showed ground-glass opacities mostly pronounced outside the radiation field. Conclusions As this pandemic continues, patients with symptoms of RP require diagnostic attention. We recommend that patients suspected of RP be tested for COVID-19 before starting empiric corticosteroids and for careful attention be paid to chest CT imaging in order to prevent potential exacerbation of COVID-19 in these high-risk patients.


docid: syhjnyzo

title: Outbreakmanagement in Nederland

text: Outbreakmanagement in Nederland is vastgelegd in de Wet publieke gezondheid. De verantwoordelijkheid voor het bestrijden van lokale uitbraken ligt bij het college van burgemeester en wethouders, inhoudelijk geadviseerd door de arts infectieziektebestrijding van de GGD. Op basis van de potentiële impact en de noodzaak van wettelijk maatregelen (lees ‘dwangmaatregelen’) worden de meldingsplichtige ziekten onderverdeeld in groep A, B1, B2 en C. In geval van A-ziekten: pokken, polio, SARS en Nieuwe Influenza A/H1N1, komt de regie in handen van de minister van Volksgezondheid, Welzijn en Sport. Het Centrum Infectieziektebestrijding van het RIVM adviseert de minister door middel van een Outbreak Management Team (OMT). Vroege signalering en melding van aangifteplichtige ziekten, of clusters van nog onbekende oorzaak, door de arts aan de GGD is essentieel voor een adequate bestrijding.


title: Recent outbreak of chilblain‐like lesions is not directly related with SARS‐CoV‐2 infection

text: Throughout March and April 2020, dermatologists have observed an outbreak of chilblains despite climatic conditions not conducive to their apparition. These lesions have occurred simultaneously to the COVID‐19 epidemic, suggesting a relationship between their onset and SARS‐CoV‐2 infection. Here we describe a series of 10 patients presenting chilblain‐like lesions in whom we have searched for evidence of SARS‐CoV‐2 infection.


title: Emerging outbreaks associated with equine coronavirus in adult horses

text: Abstract The purpose of this study was to describe clinical, hematological and fecal PCR results from 161 horses involved in outbreaks associated with ECoV. The outbreaks happened at four separate boarding facilities between November 2011 and April 2012 in the States of CA, TX, WI and MA. Following the molecular detection of ECoV in the feces from the initial index cases, the remaining herdmates were closely observed for the development of clinical signs. Fecal samples were collected from sick and healthy horses for the PCR detection of ECoV. All four outbreaks involved primarily adult horses. Fifty-nine horses developed clinical signs with 12–16 sick horses per outbreak. The main clinical signs reported were anorexia, lethargy and fever. Four horses from 3 different outbreaks were euthanized or died due to rapid progression of clinical signs. The cause of death could not be determined with necropsy evaluation in 2 horses, while septicemia secondary to gastrointestinal translocation was suspected in 2 horses. Blood work was available from 10 horses with clinical disease and common hematological abnormalities were leucopenia due to neutropenia and/or lymphopenia. Feces were available for ECoV testing by real-time PCR from 44 and 96 sick and healthy horses, respectively. 38/44 (86%) horses with abnormal clinical signs tested PCR positive for ECoV, while 89/96 (93%) healthy horses tested PCR negative for ECoV. The overall agreement between clinical status and PCR detection of ECoV was 91%. The study results suggest that ECoV is associated with self-limiting clinical and hematological abnormalities in adult horses.


title: The turn from just-in-time to just-in-case globalization in and after times of COVID-19 An essay on the risk re-appraisal of borders and buffers

text: Abstract In this essay, we apply insights from International Economics and Economic Geography to examine how the current COVID-19 crisis may structurally change the international economy. Our key argument is that the current crisis will fundamentally change key economic actors’ risk appetite, triggering a renewed risk assessment that will lead to the comeback of buffers and borders across industries. This partial return to regionalization will involve a form of de-globalization that transforms modern just-in-time management into its just-in-case counterpart, because resilience will be priced and discounted for by enterprises and governments alike. We discuss what such a structural change will imply for the International Business of international value chains.


title: Duration of postviral airway hyperresponsiveness in children with asthma: Effect of atopy

text: Background Respiratory viruses induce asthma exacerbations and airway hyperresponsiveness (AHR). Atopy is an important risk factor for asthma persistence. Objective We sought to evaluate whether atopy is a risk factor for prolonged AHR after upper respiratory tract infections (URIs). Methods Twenty-five children (13 atopic and 12 nonatopic children) with intermittent virus-induced asthma were studied. Clinical evaluation, skin prick tests, methacholine bronchoprovocation, questionnaires, and a nasal wash specimen were obtained at baseline. For 9 months, subjects completed diary cards with respiratory symptoms. During their first reported cold, a nasal wash specimen was obtained. Methacholine provocation was performed 10 days and 5, 7, 9, and 11 weeks later. In case a new cold developed, the provocation schedule was followed from the beginning. Results Viruses were detected in 17 (68%) of 25 patients during their first cold, with rhinovirus being most commonly identified (82%). AHR increased significantly 10 days after the URI, equally in both groups (P =.67), and remained so up to the fifth week. Duration of AHR in subjects experiencing a single URI ranged from 5 to 11 weeks, without a significant difference between groups. In the duration of the study, atopic children experienced more colds and asthma exacerbations than nonatopic children. Thus for duration of AHR, significant prolongation was noted in the atopic group when assessed cumulatively. Conclusion In asthmatic children the duration of AHR after a single natural cold is 5 to 11 weeks. However, an increased rate of symptomatic cold and asthma episodes in atopic children is associated with considerable cumulative prolongation of AHR, which might help explain the role of atopy as a risk factor for asthma persistence.


title: Do Men Have a Higher Case Fatality Rate of Severe Acute Respiratory Syndrome than Women Do?

text: Severe acute respiratory syndrome (SARS) has been reported in 30 countries and regions, with a cumulative total of 8,099 probable cases and 774 deaths as of July 31, 2003, according to the World Health Organization. In Hong Kong, People’s Republic of China, 1,755 SARS cases and 299 deaths had occurred as of September 22, 2003. The authors analyzed data from the Department of Health, Hong Kong SAR. The data series includes details regarding sex, age, and chronic disease history. Using data from early March to September 22, 2003, the authors found that males had a significantly (p < 0.0001) higher case fatality rate than females did, 21.9% versus 13.2%; the relative risk was 1.66 (95% confidence interval (CI): 1.35, 2.05), and it was 1.62 (95% CI: 1.21, 2.16) after adjustment for age. Subgroup analysis was conducted by excluding health care workers (n = 386) from the analysis. The overall crude relative risk of mortality was 1.41 (95% CI: 1.15, 1.74), and the adjusted relative risk was 1.48 (95% CI: 1.10, 2.00). Thus, among SARS patients, males may be more severely affected by the disease than females are. This finding could be related to a nonuniform case definition of SARS disease, a different treatment regimen, a past smoking history, work-environment factors, or gender-specific immune-defense factors, for instance.


title: Chapter 38 Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Axis Emerging Pharmacological Target for Pulmonary Diseases

text: Abstract Experimental and clinical evidence supports an active role of the renin–angiotensin system (RAS) in the pathogenesis and progression of lung diseases. Angiotensin II (Ang II), a key vasoactive peptide of the RAS, has been implicated in pulmonary disorders such as pulmonary arterial hypertension, lung fibrosis, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Over the past few years, the classical concept of the RAS has undergone substantial changes to include several new active components. Among them, the identification of angiotensin-converting enzyme 2 (ACE2), its metabolic product angiotensin-(1-7) (Ang-(1-7)), and the Mas receptor has been of biological significance since these components form a counterregulatory axis (ACE2/Ang-(1-7)/Mas) that opposes the detrimental actions of Ang II. In this chapter, we will discuss the role of the ACE2/Ang-(1-7)/Mas axis in lung diseases and describe novel therapeutic approaches to activate this axis for the treatment of pulmonary disorders.


title: Predicting zoonoses

text: As the line dividing human and wild habitats becomes thinner, we might be brewing the world's next big pandemic. Zoonoses are diseases that are naturally transmitted between animals and humans, and a new project aims to predict their occurrence.


docid: haszvpis

title: SARS Epidemiology Modeling


Being the Pioneer of Life Sciences in China: —Introduction to Beijing Genomics Institute


docid: xvmpmljp

title: A mature and fusogenic form of the Nipah virus fusion protein requires proteolytic processing by cathepsin L

text: Abstract The Nipah virus fusion (F) protein is proteolytically processed to F1 + F2 subunits. We demonstrate here that cathepsin L is involved in this important maturation event. Cathepsin inhibitors ablated cleavage of Nipah F. Proteolytic processing of Nipah F and fusion activity was dramatically reduced in cathepsin L shRNA-expressing Vero cells. Additionally, Nipah virus F-mediated fusion was inhibited in cathepsin L-deficient cells, but coexpression of cathepsin L restored fusion activity. Both purified cathepsin L and B could cleave immunopurified Nipah F protein, but only cathepsin L produced products of the correct size. Our results suggest that endosomal cathepsins can cleave Nipah F, but that cathepsin L specifically converts Nipah F to a mature and fusogenic form.


title: Opinion to address a potential personal protective equipment shortage in the global community during the COVID-19 outbreak

text: Abstract The current COVID-19 pandemic is stretching the global supply situation for face masks and PPE beyond production capacity. This is a call for the R&D community, particularly in the polymer degradation and stability arena, to engage and collaborate with virology and bio-medical experts. We require comparative R&D for extended, reuse and recyclability options, as well as large scale approaches and methods that could quickly be applied on the local level by the public who are not experts and may only have limited resources.


title: Relationships between disaster nursing competence, anticipatory disaster stress and motivation for disaster engagement

text: Abstract Nurses are the largest group of healthcare providers and are often the first line responders to a disaster event. Nurses' disaster competence, motivation for disaster engagement, and factors that impact their motivation to respond to disaster events need to be understood. The purposes of the study were to determine the predictive relationships between Taiwanese nurses' disaster competence, anticipatory disaster stress, and motivation for disaster engagement. A cross-sectional design was used to analyze data collected between August 2017 and December 2017 from eight hospitals in southern Taiwan. Ninety participants who met the recruitment criteria completed and returned questionnaires with an 88.24% response rate. Data collection involved administering the Disaster Nursing Competence Questionnaire, Anticipatory Disaster Stress Questionnaire, and the Motivation of Disaster Engagement Questionnaire. The results indicated that anticipatory disaster stress was positively correlated with disaster competence and motivation for disaster engagement. Disaster competence and willingness to join a hospital disaster rescue predicts an individuals' motivation for disaster engagement. The results of the study add to the understanding of factors that correlate with nurses' motivation to participate in disaster events. By understanding these factors, the government and healthcare administrators can design disaster education plans and other strategies to improve Taiwanese nurses’ motivation to engage in disaster events.


docid: nzxbogga

title: Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post_treatment hospitalisation status

text: SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94% in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.


docid: bgcjjter

title: Applications of heteronuclear NMR spectroscopy in biological and medicinal inorganic chemistry

text: Abstract There is a wide range of potential applications of inorganic compounds, and metal coordination complexes in particular, in medicine but progress is hampered by a lack of methods to study their speciation. The biological activity of metal complexes is determined by the metal itself, its oxidation state, the types and number of coordinated ligands and their strength of binding, the geometry of the complex, redox potential and ligand exchange rates. For organic drugs a variety of readily observed spin I =1/2 nuclei can be used (1H, 13C, 15N, 19F, 31P), but only a few metals fall into this category. Most are quadrupolar nuclei giving rise to broad lines with low detection sensitivity (for biological systems). However we show that, in some cases, heteronuclear NMR studies can provide new insights into the biological and medicinal chemistry of a range of elements and these data will stimulate further advances in this area.


title: Microinjection of mRNA coding for an anti-golgi antibody inhibits intracellular transport of a viral membrane protein

text: Abstract Messenger RNA was prepared from a hybridoma cell line secreting a monoclonal antibody (53FC3) directed against a luminal epitope of a Golgi membrane protein (Mr = 135 kd) found in rodent cells. When this mRNA was microinjected into the cytoplasm of BHK cells, mouse IgG was seen to accumulate in the Golgi complex after 5–6 hr of incubation. No accumulation was seen in 3T3 cells which lack the epitope recognized by 53FC3. When microinjected BHK cells were infected with vesicular stomatitis virus, surface expression of the viral G protein was considerably reduced when compared with neighboring noninjected cells.


title: Gaussian approach for probability and correlation between the number of COVID-19 cases and the air pollution in Lima

text: At the end of February 2020, Peru started the first cases of pneumonia associated with coronavirus (COVID-19), they were reported in Lima, Peru (Rodriguez-Morales et al., 2020). Therefore, the first week on March started with 72 infected people, the government published new law for a national crisis by COVID-19 pandemic (Vizcarra et al., 2020), with a quarantine in each city of Peru. Our analysis has considered March and April 2020, for air quality measurement and infections in Lima, the data collected on 6 meteorological stations with CO (carbon monoxide), NO(2) (nitrogen oxide), O(3) (ozone), SO(2) (sulfur dioxide), PM(10) and PM(2.5) (particle matter with diameter aerodynamic less than 2.5 and 10 m respectively). As a result, the average of these concentrations and the hospital information is recollected per hour. This analysis is executed during the quarantine an important correlation is discovered in the zone with highest infection by COVID-19, NO(2) and PM(10), even though in a reduction of air pollution in Lima. In this paper, we proposed a classification model by Reduced-Space Gaussian Process Regression for air pollution and infections; with technological and environmental dynamics and global change associated COVID-19. An evaluation of zones in Lima city, results have demonstrated influence of industrial influence in air pollution and infections by COVID-19 before and after quarantine during the last 28 days since the first infection in Peru; the problems relating to data management were validated with a successful classification and cluster analysis for future works in COVID-19 influence by environmental conditions.


List of contents


Preparing for the Aftermath of COVID-19: Important Considerations for Health Care Providers and Hospital Administrators


title: Exploring the Prospects of Engineered Newcastle Disease Virus in Modern Vaccinology

text: Many traditional vaccines have proven to be incapable of controlling newly emerging infectious diseases. They have also achieved limited success in the fight against a variety of human cancers. Thus, innovative vaccine strategies are highly needed to overcome the global burden of these diseases. Advances in molecular biology and reverse genetics have completely restructured the concept of vaccinology, leading to the emergence of state-of-the-art technologies for vaccine design, development and delivery. Among these modern vaccine technologies are the recombinant viral vectored vaccines, which are known for their incredible specificity in antigen delivery as well as the induction of robust immune responses in the vaccinated hosts. Although a number of viruses have been used as vaccine vectors, genetically engineered Newcastle disease virus (NDV) possesses some useful attributes that make it a preferable candidate for vectoring vaccine antigens. Here, we review the molecular biology of NDV and discuss the reverse genetics approaches used to engineer the virus into an efficient vaccine vector. We then discuss the prospects of the engineered virus as an efficient vehicle of vaccines against cancer and several infectious diseases of man and animals.


title: Early forecasting of the potential risk zones of COVID-19 in China's megacities

text: Recently, the coronavirus disease 2019 (COVID-19) has become a worldwide public health threat. Early and quick identification of the potential risk zones of COVID-19 infection is increasingly vital for the megacities implementing targeted infection prevention and control measures. In this study, the communities with confirmed cases during January 21–February 27 were collected and considered as the specific epidemic data for Beijing, Guangzhou, and Shenzhen. We evaluated the spatiotemporal variations of the epidemics before utilizing the ecological niche models (ENM) to assemble the epidemic data and nine socioeconomic variables for identifying the potential risk zones of this infection in these megacities. Three megacities were differentiated by the spatial patterns and quantities of infected communities, average cases per community, the percentages of imported cases, as well as the potential risks, although their COVID-19 infection situations have been preliminarily contained to date. With higher risks that were predominated by various influencing factors in each megacity, the potential risk zones coverd about 75% to 100% of currently infected communities. Our results demonstrate that the ENM method was capable of being employed as an early forecasting tool for identifying the potential COVID-19 infection risk zones on a fine scale. We suggest that local hygienic authorities should keep their eyes on the epidemic in each megacity for sufficiently implementing and adjusting their interventions in the zones with more residents or probably crowded places. This study would provide useful clues for relevant hygienic departments making quick responses to increasingly severe epidemics in similar megacities in the world.


title: Rapid detection of taxonomically important fatty acid methyl ester and steroid biomarkers using in situ thermal hydrolysis/methylation mass spectrometry (THM-MS): implications for bioaerosol detection

text: Abstract Implications for the rapid interrogation of biological materials collected from the atmosphere using a simple, one step, sample preparation technique was explored. For this purpose, various samples of whole bacteria, fungi, pollen, media contaminated with viruses, and proteins were treated with an aliquot of methanolic tetramethylammonium hydroxide prior to thermal introduction into the ion source of a triple quadrupole mass spectrometer. Molecular and fragment ions, consistent with fatty acid methyl esters (FAMEs) and steroids (non-methylated and methylated), generated during electron ionization (70 eV) of the volatile hydrolysates were subsequently detected. The varying distributions and relative intensities of these ions were used to discriminate between the different biological samples. More specifically, it was found that polyunsaturated FAMEs and steroids could be used to differentiate eukaryotic cells from prokaryotic cells since the latter do not generally synthesize either of these lipid membrane constituents. Further discrimination of the different eukaryotic samples was made based on the detection of ergosterol for fungi, cholesterol for the viral media, and C18:3Me for pollen. Multivariate statistical analysis was employed to evaluate and compare the large set of mass spectra generated during the study and to build a trained model for predicting the class membership of test samples entered as unknowns. Of 132 different samples subjected to the model as unknowns, 131 were correctly classified into their proper biological categories. Moreover, 29 out of 30 bacteria test samples representing five species of pathogenic bacteria were correctly classified at the species level.


H1N1 influenza pandemic: What we did and what we learnt?


title: Conserved T-cell epitopes of respiratory syncytial virus (RSV) delivered by recombinant live attenuated influenza vaccine viruses efficiently induce RSV-specific lung-localized memory T cells and augment influenza-specific resident memory T-cell responses

text: Respiratory syncytial virus (RSV) can cause recurrent infection in people because it does not stimulate a long-lived immunological memory. There is an urgent need to develop a safe and efficacious vaccine against RSV that would induce immunological memory without causing immunopathology following natural RSV infection. We have previously generated two recombinant live attenuated influenza vaccine (LAIV) viruses that encode immunodominant T-cell epitopes of RSV M2 protein in the neuraminidase or NS1 genes. These chimeric vaccines afforded protection against influenza and RSV infection in mice, without causing pulmonary eosinophilia or inflammatory RSV disease. The current study assessed the formation of influenza-specific and RSV-specific CD4 and CD8 T-cell responses in the lungs of mice, with special attention to the lung tissue-resident memory T cell subsets (T(RM)). The RSV epitopes did not affect influenza-specific CD4 effector memory T cell (Tem) levels in the lungs. The majority of these cells formed by LAIV or LAIV-RSV viruses had CD69(+)CD103(-) phenotype. Both LAIV+NA/RSV and LAIV+NS/RSV recombinant viruses induced significant levels of RSV M2(82) epitope-specific lung-localized CD8 Tem cells expressing both CD69 and CD103 T(RM) markers. Surprisingly, the CD69(+)CD103(+) influenza-specific CD8 Tem responses were augmented by the addition of RSV epitopes, possibly as a result of the local microenvironment formed by the RSV-specific memory T cells differentiating to T(RM) in the lungs of mice immunized with LAIV-RSV chimeric viruses. This study provides evidence that LAIV vector-based vaccination can induce robust lung-localized T-cell immunity to the inserted T-cell epitope of a foreign pathogen, without altering the immunogenicity of the viral vector itself.


title: Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings

text: PURPOSE: To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings. METHODS: Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings. RESULTS: Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype. CONCLUSION: Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types.


title: Lung, Heart, Vascular, and Diaphragm Ultrasound Examination of COVID-19 Patients: A Comprehensive Approach

text: Lung ultrasound (LU) has a multitude of features and capacities that make it a useful medical tool to assist physicians contending with the pandemic spread of novel coronavirus disease-2019 (COVID-19) caused by coronavirus SARS-CoV-2. Thus, a LU approach to patients with suspected COVID-19 is being implemented worldwide. In non-critical COVID-19 patients, two new LU signs have been described and proposed: the “waterfall” and the “light beam” signs. Both signs have been hypothesized to increase the diagnostic accuracy of LU for COVID-19 interstitial pneumonia. In critically-ill patients, a distinct pattern of LU changes seems to follow the disease's progression, and this information can be used to guide decisions about when a patient needs to be ventilated, as occurs in other disease states similar to COVID-19. Furthermore, a new algorithm has been published, which enables the automatic detection of B-lines as well as quantification of the percentage of the pleural line associated with lung disease. In COVID-19 patients, a direct involvement of cardiac function has been demonstrated, and ventilator-induced diaphragm dysfunction might be present due to the prolonged mechanical ventilation often involved, as reported for similar diseases. For this reason, cardiac and diaphragm ultrasound evaluation is highly important. Last but not least, due to the thrombotic tendency of COVID-19 patients, particular attention should also be paid to vascular ultrasound. This review is primarily devoted to the study of LU in COVID-19 patients. We explain the significance of its “light and shadows”, bearing in mind the context in which LU is being used: the emergency department and the intensive care setting. The use of cardiac, vascular, and diaphragm ultrasound is also discussed, as a comprehensive approach to patient care.


title: Pulmonary embolism in patients with Covid-19 pneumonia

text: We report an overall 24%(95% CI; 17–32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients


title: Cigarette smoke exposure and inflammatory signaling increase the expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract

text: Abstract The factors mediating fatal SARS-CoV-2 infections are poorly understood. Here, we show that cigarette smoke causes a dose-dependent upregulation of Angiotensin Converting Enzyme 2 (ACE2), the SARS-CoV-2 receptor, in rodent and human lungs. Using single-cell sequencing data, we demonstrate that ACE2 is expressed in a subset of secretory cells in the respiratory tract. Chronic smoke exposure triggers the expansion of this cell population and a concomitant increase in ACE2 expression. In contrast, quitting smoking decreases the abundance of these secretory cells and reduces ACE2 levels. Finally, we demonstrate that ACE2 expression is responsive to inflammatory signaling and can be upregulated by viral infections or interferon treatment. Taken together, these results may partially explain why smokers are particularly susceptible to severe SARS-CoV-2 infections. Furthermore, our work identifies ACE2 as an interferon-stimulated gene in lung cells, suggesting that SARS-CoV-2 infections could create positive-feedback loops that increase ACE2 levels and facilitate viral dissemination.


title: Electron microscopy in the diagnosis of viral gastroenteritis in hospitalised children in the Czech Republic

text: Our study has been aimed at demonstrating the main role of viruses in the aetiology of acute gastroenteritis in children less than 5 years old and at pointing out the diagnostic potential of electron microscopy in the diagnosis of viral gastroenteritis. A prospective study was conducted to analyse the aetiology of diarrhoeal diseases in children less than 5 years of age admitted to the Department of Infectious Diseases between September 2006 and December 2008. All children were tested by faecal culture, latex agglutination and electron microscopy. A total of 832 children were included in the study. An aetiological agent was detected in 788 children (94.6 %). A bacterial aetiology was found in 22 (2.6 %) children and bacterial–viral co-infection was found in 146 (17.6 %) patients. The most frequent causative agents of gastroenteritis in children were viruses, which were detected in 620 (74.5 %) patients. The main causes of viral gastroenteritis were rotaviruses (detected in 410 children), followed by caliciviruses (42), coronaviruses (28), adenoviruses (19) and astroviruses (14). Dual viral infections were detected in 107 children, with rotavirus–calicivirus co-infection being the most common. Electron microscopy proved to be a more sensitive method in comparison with the latex agglutination test for the diagnosis of rotaviruses and adenoviruses. The major role of viruses in diarrhoeal diseases among children under 5 years of age in the Czech Republic has been confirmed. The diagnostic potential of electron microscopy, particularly in small outbreaks of gastroenteritis, was clearly shown.


title: Tracheotomy in the SARS‐CoV‐2 pandemic

text: The severe acute respiratory syndrome (SARS)‐CoV‐2 pandemic continues to produce a large number of patients with chronic respiratory failure and ventilator dependence. As such, surgeons will be called upon to perform tracheotomy for a subset of these chronically intubated patients. As seen during the SARS and the SARS‐CoV‐2 outbreaks, aerosol‐generating procedures (AGP) have been associated with higher rates of infection of medical personnel and potential acceleration of viral dissemination throughout the medical center. Therefore, a thoughtful approach to tracheotomy (and other AGPs) is imperative and maintaining traditional management norms may be unsuitable or even potentially harmful. We sought to review the existing evidence informing best practices and then develop straightforward guidelines for tracheotomy during the SARS‐CoV‐2 pandemic. This communication is the product of those efforts and is based on national and international experience with the current SARS‐CoV‐2 pandemic and the SARS epidemic of 2002/2003.


title: Inhibition in vivo of both infective Leishmania major and L. mexicana amazonensis mediated by a single monoclonal antibody

text: Abstract Monoclonal antibodies raised against a strain of Leishmania infantum isolated in Greece were produced and tested for their protective effect in an in vivo system (in BALB/C mice). A single monoclonal antibody, IgG2b isotype, can prevent the development of two Leishmania strains in vivo: one of L. major and one of L. mexicana amazonensis. This antibody-mediated protection may be dependent on complement.


title: Enabling Medicine Reuse Using a Digital Time Temperature Humidity Sensor in an Internet of Pharmaceutical Things Concept

text: Medicinal waste due to improper handling of unwanted medicines creates health and environmental risks. However, the re-dispensing of unused prescribed medicines from patients seems to be accepted by stakeholders when quality and safety requirements are met. Reusing dispensed medicines may help reduce waste, but a comprehensive validation method is not generally available. The design of a novel digital time temperature and humidity indicator based on an Internet of Pharmaceutical Things concept is proposed to facilitate the validation, and a prototype is presented using smart sensors with cloud connectivity acting as the key technology for verifying and enabling the reuse of returned medicines. Deficiency of existing technologies is evaluated based on the results of this development, and recommendations for future research are suggested.


title: Transplantation of induced neural stem cells (iNSCs) into chronically demyelinated corpus callosum ameliorates motor deficits

text: Multiple Sclerosis (MS) causes neurologic disability due to inflammation, demyelination, and neurodegeneration. Immunosuppressive treatments can modify the disease course but do not effectively promote remyelination or prevent long term neurodegeneration. As a novel approach to mitigate chronic stage pathology, we tested transplantation of mouse induced neural stem cells (iNSCs) into the chronically demyelinated corpus callosum (CC) in adult mice. Male C57BL/6 mice fed 0.3% cuprizone for 12 weeks exhibited CC atrophy with chronic demyelination, astrogliosis, and microglial activation. Syngeneic iNSCs were transplanted into the CC after ending cuprizone and perfused for neuropathology 2 weeks later. Magnetic resonance imaging (MRI) sequences for magnetization transfer ratio (MTR), diffusion-weighted imaging (T2), and diffusion tensor imaging (DTI) quantified CC pathology in live mice before and after iNSC transplantation. Each MRI technique detected progressive CC pathology. Mice that received iNSCs had normalized DTI radial diffusivity, and reduced astrogliosis post-imaging. A motor skill task that engages the CC is Miss-step wheel running, which demonstrated functional deficits from cuprizone demyelination. Transplantation of iNSCs resulted in marked recovery of running velocity. Neuropathology after wheel running showed that iNSC grafts significantly increased host oligodendrocytes and proliferating oligodendrocyte progenitors, while modulating axon damage. Transplanted iNSCs differentiated along astrocyte and oligodendrocyte lineages, without myelinating, and many remained neural stem cells. Our findings demonstrate the applicability of neuroimaging and functional assessments for pre-clinical interventional trials during chronic demyelination and detect improved function from iNSC transplantation. Directly reprogramming fibroblasts into iNSCs facilitates the future translation towards exogenous autologous cell therapies.


title: Clematis montana lectin, a novel mannose-binding lectin from traditional Chinese medicine with antiviral and apoptosis-inducing activities

text: A novel mannose-binding lectin (designated CML) was isolated from Clematis montana Buch.-Ham stem (Ranunculaceae) using ion exchange and gel filtration chromatographies on DEAE-Sepharose and Sephacryl S-100. The purified C. montana lectin was a homodimer of 11,968.9 Da subunits as determined by gel filtration and MS. The hemagglutinating activity of CML was inhibited by branched oligomannosides. The N-terminal 15-amino acid sequence of CML, DNVKYSGQVKNTGSA, has not been reported for other lectins. Also, the peptide mass fingerprinting assay confirmed that there is no match result of similar plant lectins for CML, indicating CML may be a novel plant lectin. CML showed marked antiviral activity against various viruses in cell culture. Subsequently, CML was also found to exhibit remarkable inhibitory effect on L929, HeLa, MCF7 and HepG2 cells. Furthermore, CML specially induced L929 cell apoptosis in dose-dependent manner as evidenced by MTT, fluorescent microscopy, LDH activity-based cytotoxicity assays and DNA ladder. Moreover, due to both caspase inhibitors and Western blot analyses, caspase was also found to play the important role in the potential apoptotic mechanism of CML. When the carbohydrate-binding site was fully inhibited by sugars, cytotoxicity was abruptly decreased and apoptotic phenomenon in L929 cells was not observed, suggesting a significant correlation between mannose-binding-specific activity and the antineoplastic mechanism.


title: Setting up and maximising the usage of an Urgent Dental Care Centre in Blackpool. Sharing our experiences

text: An integrated Urgent Dental Care Centre with Tier 2 Oral Surgery support was set up in Blackpool starting 24(th) March 2020. This was in reaction to the COVID-19 pandemic. In the first month 1433 patients had telephone consultations and 713 extractions were performed. The challenges surrounding set up and continuity of care are discussed.


title: Application of ProteinChip Array Profiling in Serum Biomarker Discovery for Patients Suffering From Severe Acute Respiratory Syndrome

text: A new strain of coronavirus has caused an outbreak of severe acute respiratory syndrome (SARS) from 2002 to 2003 resulting in 774 deaths worldwide. By protein chip array profiling technology, a number of serum biomarkers that might be useful in monitoring the clinical course of SARS patients were identified. This book chapter describes how the protein chip array profiling was carried out for this study. Briefly, SARS patients’ serum samples were first fractionated in Q Ceramic HyperD ion exchange sorbent beads by buffers at different pH. Serum protein fractions thus obtained were then bound onto a copper (II) immobilized metal affinity capture (IMAC30 Cu [II]) ProteinChip® Array or a weak cation-exchange (CM10) ProteinChip Array. After washing and addition of sinapinic acid, the chips were read in a Protein Biological System (PBS) IIc mass spectrometer. Ions were generated by laser shots and flied in a time of flight mode to the ion detector according to their mass over charge (m/z) ratio. The serum profiling spectra in SARS patients were acquired, baseline subtracted and analyzed in parallel with those from the control subjects by Ciphergen ProteinChip Software 3.0.2 with their peak intensities compared by a nonparametric two sample Mann-Whitney-U test. More than twelve peaks were differentially expressed in SARS patients with one at m/z of 11,695 (later identified to be serum amyloid A protein), which had increase in peak intensity correlating with the extent of SARS-coronavirus induced pneumonia as defined by a serial chest X-ray opacity score. The remaining biomarkers could also be useful in the study of other clinical parameters in SARS patients.


title: Gendered effects on inflammation reaction and outcome of COVID‐19 patients in Wuhan

text: BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID‐19) has turned into a public health emergency of international concern. Epidemiological research showed that gender was associated with the severity of COVID‐19, but the underlying mechanism of gender predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID‐19. METHODS: In this retrospective study, we enrolled 548 COVID‐19 inpatients from Tongji Hospital from January 26 to February 5, 2020, and followed up to March 3, 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. Cox proportional hazard regression model was applied to identify gendered effect on mortality of COVID‐19 after adjusting age, comorbidity and smoking history. Multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs. 10.4%), with the HR of 1.923 (95% CI, 1.181‐3.130); elder age and comorbidity were significantly associated with decease of COVID‐19 patients. Excess inflammation reaction was related to severity of COVID‐19. Male patients had greater inflammation reaction, with higher levels of IL‐10, TNF‐α, LDH, ferritin and hsCRP, but lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Gender, age, and comorbidity are critical risk factors for mortality of COVID‐19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males especially elder males to develop cytokine storm, causing potential ARDS, multiple organ failure and decease. This article is protected by copyright. All rights reserved.


title: Sensing social interactions through BLE beacons and commercial mobile devices

text: Wearable sensing devices can provide high-resolution data useful to characterise and identify complex human behaviours. Sensing human social interactions through wearable devices represents one of the emerging field in mobile social sensing, considering their impact on different user categories and on different social contexts. However, it is important to limit the collection and use of sensitive information characterising individual users and their social interactions in order to maintain the user compliance. For this reason, we decided to focus mainly on physical proximity and, specifically, on the analysis of BLE wireless signals commonly used by commercial mobile devices. In this work, we present the SocializeME framework designed to collect proximity information and to detect social interactions through heterogeneous personal mobile devices. We also present the results of an experimental data collection campaign conducted with real users, highlighting technical limitations and performances in terms of quality of RSS, packet loss, and channel symmetry, and how they are influenced by different configurations of the user’s body and the position of the personal device. Specifically, we obtained a dataset with more than 820.000 Bluetooth signals (BLE beacons) collected, with a total monitoring of over 11 h. The dataset collected reproduces 4 different configurations by mixing two user posture’s layouts (standing and sitting) and different positions of the receiver device (in hand, in the front pocket and in the back pocket). The large number of experiments in those different configurations, well cover the common way of holding a mobile device, and the layout of a dyad involved in a social interaction. We also present the results obtained by SME-D algorithm, designed to automatically detect social interactions based on the collected wireless signals, which obtained an overall accuracy of 81.56% and F-score 84.7%. The collected and labelled dataset is also released to the mobile social sensing community in order to evaluate and compare new algorithms.


title: The Relationship of Rhinovirus-Associated Asthma Hospitalizations with Inhaled Corticosteroids and Smoking

text: BackgroundAlthough rhinovirus (RV) respiratory infections trigger asthma exacerbations, the etiologic association between this virus and severe exacerbations, as well as the clinical characteristics of adults at risk for RV-associated asthma that necessitates hospitalization, have not been established MethodsDuring 1999–2003, we conducted a cohort study of 101 adults prospectively enrolled at hospital admission for an asthma exacerbation. Patient characteristics and frequencies of RV in nasal specimens were analyzed, by reverse-transcription polymerase chain reaction (RT-PCR), at asthma-related hospital admission and at a 3-month convalescent follow-up visit ResultsRV was detected by RT-PCR in 21% of hospitalized patients over a 4-year period and in 1.3% of patients who returned for a 3-month follow-up visit. RV detection was strongly associated with hospitalization for asthma (adjusted odds ratio [OR], 15.1 [95% confidence interval {CI}, 1.88–121.4]). After adjustment for baseline asthma severity, RV-positive patients were more likely than RV-negative patients to be current smokers and nonusers of inhaled corticosteroids (ICSs) (adjusted OR, 11.18 [95% CI, 2.37–52.81]; P=.002) ConclusionsRV respiratory infection is an etiologic agent in severe asthma exacerbations necessitating hospitalization in adults. Compared with hospitalized patients with asthma who were RV negative, RV-positive patients were significantly more likely to be smokers and nonusers of ICSs


title: Meeting critical challenges and striving for urban sustainability in China

text: Abstract China has experienced outstanding economic growth during the last three decades through urbanization. But at the same time, many ecological and social issues have been marginalized, leading to problems in public safety, health, and social equity. Such a pattern of development is unlikely to be sustainable. In this article, we examine these issues and the challenges that come with resolving them, and advocate a holistic and pragmatic approach to the research and practice of urban sustainability in China.


title: Translating transmissibility measures into recommendations for coronavirus prevention

text: The rapid increase in clinical cases of the new coronavirus disease, COVID-19, suggests high transmissibility. However, the estimates of the basic reproductive number reported in the literature vary widely. Considering this, we drew the function of contact-rate reduction required to control the transmission from both detectable and undetectable sources. Based on this, we offer a set of recommendations for symptomatic and asymptomatic populations during the current pandemic. Understanding the dynamics of transmission is essential to support government decisions and improve the community’s adherence to preventive measures.


Considerations Left behind Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Outbreaks in Republic of Korea


docid: afkeuwup

title: Chapter 2 Emergency Management of Poisoning


title: Atualização em pneumonia comunitária viral()

text: Viral pneumonia is a prevalent cause of respiratory infection in immunocompetent adults. It has varied presentation, from mild to severe respiratory failure, requiring mechanical ventilation. However, in Brazil, there have been few studies on the clinical presentation and diagnosis of this infection. Thus, the authors of the present article intend to review the main viral agents that cause community-acquired pneumonia and to discuss the currently available diagnostic and therapeutic methods.


title: An updated analysis of turning point, duration and attack rate of COVID-19 outbreaks in major Western countries with data of daily new cases

text: As coronavirus spreads around the world, the study of its effects is of great practical significance. We collated data on daily new cases of the COVID-19 outbreaks in the six Western countries of the Group of Seven and the dates of governments’ interventions. We studied the periods before and after the dates of major governments’ interventions integrally based on a segmented Poisson model. The relevant results are published in the paper of “Predicting turning point, duration and attack rate of COVID - 19 outbreaks in major Western countries” [1]. Our method can be used to update prediction daily as COVID-19 outbreaks evolve. In this article, we illustrate an updated analysis with our method to facilitate reproducibility. Both datasets used and updated are provided.


title: Nrf2 Activator PB125® as a Potential Therapeutic Agent Against COVID-19

text: Nrf2 is a transcription factor that regulates cellular redox balance and the expression of a wide array of genes involved in immunity and inflammation, including antiviral actions. Nrf2 activity declines with age, making the elderly more susceptible to oxidative stress-mediated diseases, which include type 2 diabetes, chronic inflammation, and viral infections. Published evidence suggests that Nrf2 activity may regulate important mechanisms affecting viral susceptibility and replication. We examined gene expression levels by GeneChip microarray and by RNA-seq assays. We found that the potent Nrf2 activating composition PB125® downregulates ACE2 and TMPRSS2 mRNA expression in human liver-derived HepG2 cells. ACE2 is a surface receptor and TMPRSS2 activates the spike protein for SARS-Cov-2 entry into host cells. Furthermore, in endotoxin-stimulated primary human pulmonary artery endothelial cells we report the marked downregulation by PB125 of 36 genes encoding cytokines. These include IL1-beta, IL6, TNF-α the cell adhesion molecules ICAM1, VCAM1, and E-selectin, and a group of IFN-γ-induced genes. Many of these cytokines have been specifically identified in the “cytokine storm” observed in fatal cases of COVID-19, suggesting that Nrf2 activation may significantly decrease the intensity of the storm.


title: A perspective on hydrothermal processing of sewage sludge

text: Abstract The US annually produces 79 million dry tons of liquid organic waste including sewage sludge. Anaerobic digestion can only reduce the sludge volume by 50% in mass, leaving the other half as a growing waste management and hygienic problem. Hydrothermal processing (HTP), a set of several chemical digestion processes, could be used to convert sewage sludge into valuable products and minimize potential environmental pollution risks. Specifically, hydrothermal carbonization and hydrothermal liquefaction have been extensively studied to sustainably manage sludge. Two of the main reasons for this are the high upscalability of HTP for public waste management and that it is estimated that HTP can recover eleven times more energy from waste products than landfilling. An integration of HTP with anaerobic digestion or recycling the soluble organics (in the HTP aqueous products) into the HTP process could lead to a higher overall rate of energy recovery for municipal sewage sludge.


title: Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

text: We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.


title: Fusogenicity of the Ghana Virus (Henipavirus: Ghanaian bat henipavirus) Fusion Protein is Controlled by the Cytoplasmic Domain of the Attachment Glycoprotein

text: The Ghana virus (GhV) is phylogenetically related to the zoonotic henipaviruses Nipah (NiV) and Hendra virus. Although GhV uses the highly conserved receptor ephrin-B2, the fusogenicity is restricted to cell lines of bat origin. Furthermore, the surface expression of the GhV attachment glycoprotein (G) is reduced compared to NiV and most of this protein is retained in the endoplasmic reticulum (ER). Here, we generated truncated as well as chimeric GhV G proteins and investigated the influence of the structural domains (cytoplasmic tail, transmembrane domain, ectodomain) of this protein on the intracellular transport and the fusogenicity following coexpression with the GhV fusion protein (F). We demonstrate that neither the cytoplasmic tail nor the transmembrane domain is responsible for the intracellular retention of GhV G. Furthermore, the cytoplasmic tail of GhV G modulates the fusogenicity of GhV F and therefore controls the species-restricted fusogenicity of the GhV surface glycoproteins.


title: Considerations for Development and Use of AI in Response to COVID-19

text: Artificial intelligence (AI) is playing a key supporting role in the fight against COVID-19 and perhaps will contribute to solutions quicker than we would otherwise achieve in many fields and applications. Since the outbreak of the pandemic, there has been an upsurge in the exploration and use of AI, and other data analytic tools, in a multitude of areas. This paper addresses some of the many considerations for managing the development and deployment of AI applications, including planning; unpredictable, unexpected, or biased results; repurposing; the importance of data; and diversity in AI team membership. We provide implications for research and for practice, according to each of the considerations. Finally we conclude that we need to plan and carefully consider the issues associated with the development and use of AI as we look for quick solutions.


title: GI-16 lineage (624/I or Q1), there and Back Again: the history of one of the major threat for poultry farming of our era

text: The genetic variability of Infectious bronchitis virus (IBV) is one of the main challenges for its control, hindering not only the development of effective vaccination strategies but also its classification and, consequently, epidemiology understanding. The 624/I and Q1 genotypes, now recognized to be part of the GI-16 lineage, represent an excellent example of the practical consequences of IBV molecular epidemiology limited knowledge. In fact, being their common origin unrecognized for a long time, independent epidemiological pictures were drawn for the two genotypes. To fix this misinterpretation, the present study reconstructs the history, population dynamics and spreading patterns of GI-16 lineage as a whole using a phylodynamic approach. A collection of worldwide available hypervariable region 1 and 2 (HVR12) and 3 (HVR3) sequences of the S1 protein was analysed together with 258 HVR3 sequences obtained from samples collected in Italy (the country where this genotype was initially identified) since 1963. The results demonstrate that after its emergence at the beginning of the XX century, GI-16 was able to persist until present days in Italy. Approximately in the late 1980s, it migrated to Asia, which became the main nucleus for further spreading to Middle East, Europe and especially South America, likely through multiple introduction events. A remarkable among-country diffusion was also demonstrated in Asia and South America. Interestingly, although most of the recent Italian GI-16 strains originated from ancestral viruses detected in the same country, a couple were closely related to Chinese ones, supporting a backward viral flow from China to Italy. Besides to the specific case-study results, this work highlights the misconceptions that originate from the lack of a unified nomenclature and poor molecular epidemiology data generation and sharing. This shortcoming appears particularly relevant since the described scenario could likely be shared by many other IBV genotypes and pathogens in general.


title: Association between social support and recovery from post-traumatic stress disorder after flood: a 13–14 year follow-up study in Hunan, China

text: BACKGROUND: Post-traumatic stress disorder (PTSD) is one of the most prevalent long-term psychiatric disorders among survivors of traumatic events. It is well established that social support has been related to the onset of PTSD after natural disasters. However, very little is known whether or not social support has had an influence on the recovery from the PTSD that was diagnosed after floods. This study, therefore, made a follow-up assessment of PTSD in flood victims 13–14 years after they were diagnosed with PTSD in 2000 to measure the prevalence rate of PTSD among them and identify the association between social support and their recovery from PTSD. METHODS: Victims who had experienced Dongting Lake flood in 1998 and had been diagnosed as having PTSD in 2000 were enrolled in this study. A follow-up survey was done between the years 2013 and 2014 to diagnose the victims again of PTSD using the DSM-IV criteria. Social support and its three dimensions were measured using the Chinese version of Social Support Rating Scale (SSRS), including objective support, subjective support and support utilization. Data were collected through face-to-face interviews using a structured questionnaire. Bivariate and multivariate logistic regression analyses were used to examine the relationship between social support and the recovery from PTSD after flood. RESULTS: Out of 321 subjects with prior PTSD, 51 (15.89 %) were diagnosed as still having PTSD. Logistic regression analyses indicated that the recovery from prior PTSD was significantly associated with social support (odds ratio (OR) =0.202, 95 % confidence interval (95 % CI): 0.047–0.878), subjective support (OR = 0.236, 95 % CI: 0.080–0.694) and support utilization (OR = 0.245, 95 % CI: 0.071–0.844). CONCLUSIONS: The prevalence rate of current PTSD indicates that natural disasters, such as floods, may affect the mental health of victims for a long time. Social support was significantly associated with the recovery from prior PTSD, especially subjective support and support utilization.