title: Amelioration of Japanese encephalitis by blockage of 4-1BB signaling is coupled to divergent enhancement of type I/II IFN responses and Ly-6C(hi) monocyte differentiation

text: BACKGROUND: Japanese encephalitis (JE), a neuroinflammation caused by zoonotic JE virus, is the major cause of viral encephalitis worldwide and poses an increasing threat to global health and welfare. To date, however, there has been no report describing the regulation of JE progression using immunomodulatory tools for developing therapeutic strategies. We tested whether blocking the 4-1BB signaling pathway would regulate JE progression using murine JE model. METHODS: Infected wild-type and 4-1BB-knockout (KO) mice were examined daily for mortality and clinical signs, and neuroinflammation in the CNS was evaluated by infiltration of inflammatory leukocytes and cytokine expression. In addition, viral burden, JEV-specific T cell, and type I/II IFN (IFN-I/II) innate responses were analyzed. RESULTS: Blocking the 4-1BB signaling pathway significantly increased resistance to JE and reduced viral burden in extraneural tissues and the CNS, rather than causing a detrimental effect. In addition, treatment with 4-1BB agonistic antibody exacerbated JE. Furthermore, JE amelioration and reduction of viral burden by blocking the 4-1BB signaling pathway were associated with an increased frequency of IFN-II-producing NK and CD4(+) Th1 cells as well as increased infiltration of mature Ly-6C(hi) monocytes in the inflamed CNS. More interestingly, DCs and macrophages derived from 4-1BB KO mice showed potent and rapid IFN-I innate immune responses upon JEV infection, which was coupled to strong induction of PRRs (RIG-I, MDA5), transcription factors (IRF7), and antiviral ISG genes (ISG49, ISG54, ISG56). Further, the ablation of 4-1BB signaling enhanced IFN-I innate responses in neuron cells, which likely regulated viral spread in the CNS. Finally, we confirmed that blocking the 4-1BB signaling pathway in myeloid cells derived from hematopoietic stem cells (HSCs) played a dominant role in ameliorating JE. In support of this finding, HSC-derived leukocytes played a dominant role in generating the IFN-I innate responses in the host. CONCLUSIONS: Blocking the 4-1BB signaling pathway ameliorates JE via divergent enhancement of IFN-II-producing NK and CD4(+) Th1 cells and mature Ly-6C(hi) monocyte infiltration, as well as an IFN-I innate response of myeloid-derived cells. Therefore, regulation of the 4-1BB signaling pathway with antibodies or inhibitors could be a valuable therapeutic strategy for the treatment of JE.


Nature, artifice and emerging diseases


title: 2019 novel Coronavirus outbreak: a quiz or final exam?

text: The 2019 novel Coronavirus (2019-nCoV) is an emerging pathogen and is threatening the global health. Strikingly, more than 28 000 cases and 550 deaths have been reported within two months from disease emergence. Armed with experience from previous epidemics in the last two decades, clinicians, scientists, officials, and citizens in China are all contributing to the prevention of further 2019-nCoV transmission. Efficient preliminary work has enabled us to understand the basic characteristics of 2019-nCoV, but there are still many unanswered questions. It is too early now to judge our performance in this outbreak. Continuous and strengthened efforts should be made not only during the epidemic, but also afterwards in order to prepare for any incoming challenges.


The internet hospital: an emerging innovation in China


title: Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya

text: We describe the first genome isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels (82.37%, 95% confidence interval (CI) 79.50–84.91). More female camels were significantly seropositive (74.28%, 95% CI 71.14–77.19) than male camels (P < 0.001) (53.74%, 95% CI 48.48–58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERS-CoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0076-4) contains supplementary material, which is available to authorized users.


title: First detection of adenovirus in the vampire bat (Desmodus rotundus) in Brazil

text: This paper describes the first detection of adenovirus in a Brazilian Desmodus rotundus bat, the common vampire bat. As part of a continuous rabies surveillance program, three bat specimens were captured in Southern Brazil. Total DNA was extracted from pooled organs and submitted to a nested PCR designed to amplify a 280 bp long portion of the DNA polymerase gene of adenoviruses. One positive sample was subjected to nucleotide sequencing, confirming that this DNA fragment belongs to a member of the genus Mastadenovirus. This sequence is approximately 25 % divergent at the nucleotide level from equine adenovirus 1 and two other recently characterized bat adenoviruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11262-013-0947-6) contains supplementary material, which is available to authorized users.


title: Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit

text: BACKGROUND: After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital. METHODS: Since the ICU renovation, all patients colonized or infected with MRSA were nursed in single rooms with contact precautions. The incidence of MRSA infection in the ICU was monitored during 3 different phases: the baseline period (phase 1); after ICU renovation (phase 2) and after implementation of a hand hygiene campaign with alcohol-based hand rub (phase 3). Patients infected with extended spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella species were chosen as controls because they were managed in open cubicles with standard precautions. RESULTS: Without a major change in bed occupancy rate, nursing workforce, or the protocol of environmental cleansing throughout the study period, a stepwise reduction in ICU onset nonbacteraemic MRSA infection was observed: from 3.54 (phase 1) to 2.26 (phase 2, p = 0.042) and 1.02 (phase 3, p = 0.006) per 1000-patient-days. ICU onset bacteraemic MRSA infection was significantly reduced from 1.94 (phase 1) to 0.9 (phase 2, p = 0.005) and 0.28 (phase 3, p = 0.021) per 1000-patient-days. Infection due to ESBL-producing organisms did not show a corresponding reduction. The usage density of broad-spectrum antibiotics and fluoroquinolones increased from phase 1 to 3. However a significant trend improvement of ICU onset MRSA infection by segmented regression analysis can only be demonstrated when comparison was made before and after the severe acute respiratory syndrome (SARS) epidemic. This suggests that the deaths of fellow healthcare workers from an occupational acquired infection had an overwhelming effect on their compliance with infection control measures. CONCLUSION: Provision of single room isolation facilities and promotion of hand hygiene practice are important. However compliance with infection control measures relies largely on a personal commitment, which may increase when personal safety is threatened.


title: Adaptive immune cells temper initial innate responses

text: Toll-like receptors (TLRs) recognize conserved microbial structures called pathogen-associated molecular patterns. Signaling from TLRs leads to upregulation of co-stimulatory molecules for better priming of T cells and secretion of inflammatory cytokines by innate immune cells1–4. Lymphocytedeficient hosts often die of acute infection, presumably owing to their lack of an adaptive immune response to effectively clear pathogens. However, we show here that an unleashed innate immune response due to the absence of residential T cells can also be a direct cause of death. Viral infection or administration of poly(I:C), a ligand for TLR3, led to cytokine storm in T-cell- or lymphocyte-deficient mice in a fashion dependent on NK cells and tumor necrosis factor. We have further shown, through the depletion of CD4(+) and CD8(+) cells in wild-type mice and the transfer of T lymphocytes into Rag-1–deficient mice, respectively, that T cells are both necessary and sufficient to temper the early innate response. In addition to the effects of natural regulatory T cells, close contact of resting CD4(+)CD25(−)Foxp3(−) or CD8(+) T cells with innate cells could also suppress the cytokine surge by various innate cells in an antigen-independent fashion. Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses.


title: Response to: Optimizing Hydroxychloroquine Dosing for Patients With COVID‐19: An Integrative Modeling Approach for Effective Drug Repurposing: Quantitative Clinical Pharmacology Input to SARS‐CoV‐2 Therapeutics Should Be Based on Robust Data

text: With impressive speed Garcia-Cremades et al[1] have modelled the association between hydroxychloroquine (HCQ) and viral load, merging literature in vitro data and data from a recently published clinical study (which as of April 11 2020 is under investigation by the publisher[2]). Whilst the authors are to be commended on bringing quantitative clinical pharmacology insight to this health emergency, caution is required on interpreting their results.


title: The clinical benefit of instituting a prospective clinical community-acquired respiratory virus surveillance program in allogeneic hematopoietic stem cell transplantation

text: Abstract Background There is a lack of studies comparing clinical outcomes among retrospective versus prospective cohorts of allogeneic stem cell transplant (allo-HCT) recipients with community acquired respiratory virus (CARV) infections. Methods We compare outcomes in two consecutive cohorts of allo-HCT recipients with CARV infections. The retrospective cohort included 63 allo-HCT recipients with 108 CARV infections from January 2013 to April 2016 who were screened and managed following standard clinical practice based on influenza and respiratory syncytial virus rapid antigen detection methods. The prospective cohort was comprised of 144 consecutive recipients with 297 CARV episodes included in a prospective interventional clinical surveillance program (ProClinCarvSur-P) based on syndromic multiplex PCR as first-line test from May 2016 to December 2018 at a single transplant center. Results CARV infections in the retrospective cohort showed more severe clinical features at the time of diagnosis compared to the prospective cohort (fever 83% vs. 57%, hospital admission 69% vs. 28% and lower respiratory tract 58% vs. 31%, respectively, p ≤ 0.002 for all comparisons). Antiviral therapy was more commonly prescribed in the prospective cohort (69 vs. 43 treated CARV episodes), particularly at the upper respiratory tract disease stage (34 vs. 12 treated CARV episodes). Three-month all-cause mortality was significantly higher in the retrospective cohort (n = 23, 37% vs. n = 10, 7%, p < 0.0001). Multivariate logistic regression analysis showed that recipients included in ProClinCarvSur-P had lower mortality rate [odds ratio 0.31, 95% confidence interval 0.12–0.7, p = 0.01]. Conclusion This study report on outcome differences when reporting retrospective vs. prospective CARV infections after allo-HCT. Recipients included in a ProClinCarvSur-P had lower mortality.


title: Prospective vaccination of COVID-19 using shRNA-plasmid-LDH nanoconjugate

text: COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today’s era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.


title: Both Cerebral and Hematopoietic Deficiencies in CCR2 Result in Uncontrolled Herpes Simplex Virus Infection of the Central Nervous System in Mice

text: CCR2 is a chemokine receptor expressed on the surface of blood leukocytes, particularly «Ly6C(hi)» inflammatory monocytes and microglia. Signaling through this receptor is thought to influence the immune activity of microglia as well as monocytes egress from the bone marrow (BM) and their trafficking into the central nervous system (CNS) in several neurological diseases. During experimental herpes simplex virus 1 (HSV-1) encephalitis (HSE), CCR2 deficiency has been reported to exacerbate the outcome of the disease. However, the precise contribution of CCR2 expressed in cells of the CNS or peripheral monocytes in the protection against HSE remains unclear. To dissect the differential role of CCR2 during HSE, chimeric mice with receptor deficiency in the brain or blood cells were generated by transplanting wild-type (WT) C57BL/6 or CCR2(-/-) BM-derived cells in CCR2(-/-) (WT→CCR2(-/-)) and WT (CCR2(-/-)→WT) mice, respectively. Our results indicate that following intranasal infection with 1.2x10(6) plaque forming units of HSV-1, CCR2 deficiency in hematopoietic cells and, to a lesser extent, in CNS exacerbates the outcome of HSE. Mortality rates of CCR2(-/-) (71.4%) and CCR2(-/-)→WT (57.1%) mice were significantly higher than that of WT (15.3%; P<0.01 and P<0.05, respectively) but the difference did not reach statistical significance for WT→CCR2(-/-) animals (42.8%; P = 0.16). Both peripheral and CNS deficiencies in CCR2 resulted in increased infectious viral titers and wider dissemination of HSV antigens in the brain as well as an overproduction of inflammatory cytokines and chemokines including IL-1β, IL-6, CCL2, CCL3 and CCL5. Furthermore, CCR2 deficiency in the hematopoietic system altered monocytes egress from the BM and their recruitment to the CNS, which may contribute to the failure in HSV-1 containment. Collectively, these data suggest that CCR2 expressed on cells of CNS and especially on peripheral monocytes is important for the control of HSV-1 replication and inflammatory environment during experimental HSE.


title: Urticarial eruption in COVID‐19 infection

text: Coronavirus disease (COVID‐19) is spreading quickly across the world, until a pandemic condition was announced by the WHO on March. Many clinical manifestations of this virus are described and new symptoms are emerging particularly outside respiratory sphere, such as anosmia and ageusia which are recent ORL published symptoms. About skin manifestation, few cases of rashes on patients with laboratory‐confirmed Covid‐19 were described in two Chineses cohorts.


Extracorporeal Membrane Oxygenation – Crucial Considerations during the Coronavirus Crisis


title: The polypeptide composition of avian infectious bronchitis virus particles

text: Egg grown avian infectious bronchitis virus (IBV) centrifuged on sucrose density gradients was found to consist of a major virus peak of density 1.17 to 1.18 g/cm(3) and occasionally two minor virus peaks of density 1.21 to 1.22 g/cm(3) and 1.13 g/cm(3). Three different IBV strains were examined and no morphological differences were detected between virus particles of different densities or from different strains. The polypeptides of the different density virus particles from the three IBV strains were analysed on polyacrylamide gels. In all cases 7 polypeptides were observed, although there were differences in the proportions of these polypeptides in particles of different densities and those from the different strains. The polypeptides have been called VP1 (molecular weight 130,000), VP2 (105,000), VP3 (97,000), VP4 (81,000), VP5 (74,000), VP6 (51,000) and VP7 (33,000). Additional polypeptides were produced if slightly harsher treatments were used.


Coordinating the clinical management of imported human cases suspected of being infected with a highly pathogenic virus such as Ebola


title: Pulmonary Function and Clinical Manifestations of Patients Infected with Mild Influenza A Virus Subtype H1N1: A One-Year Follow-Up

text: OBJECTIVE: To investigate the long-term effects of mild H1N1 influenza infection on the pulmonary function of a cohort of patients. METHODS: Forty-eight patients, all diagnosed with influenza A virus subtype H1N1 in 2009, were retrospectively included in this study. Each patient in the study was monitored for 11-13 months by standard pulmonary function examination. The examination included monitoring respiratory tract infection symptoms (cough, expectoration or gasping) and vital signs. Long-term changes in symptoms and changes in vital signs were correlated back to and compared with the severity of the initial H1N1 influenza infection. RESULTS: One year post discharge, mild to moderate pulmonary dysfunction was observed in the majority of patients. Further, 54.2% of patients had signs of severe abnormal pulmonary function, including diffusion disorder (33.3%) and small airway dysfunction (33.3%). Fourteen patients presented with respiratory tract infection symptoms; 12 with abnormal pulmonary function and two with normal pulmonary function. Our results indicated that the change in pulmonary function at one year post discharge was not significantly correlated with the severity of H1N1 influenza. CONCLUSION: Signs and symptoms of abnormal pulmonary function accompanied by respiratory tract infection symptoms remain for some patients after one year following discharge from the hospital for mild influenza A virus subtype H1N1 infection. These patients should continue to be monitored for any changes in condition and symptoms and rehabilitation treatment should be provided when necessary.


title: Advantages of Using Lotteries to Select Participants for High‐Demand Covid‐19 Treatment Trials

text: As hospitals have experienced a surge of Covid‐19 patients, investigators of Covid‐19 treatment trials face a difficult problem: when an institution has more eligible and interested patients than trial slots, who should be enrolled? Defining a clear strategy for selecting participants for “high‐demand” Covid‐19 treatment trials is important to avoid ad hoc and potentially biased decision‐making by local investigators, which could inadvertently compromise a trial's social value, participants' interests, or fairness. In this article, we propose a set of ethical criteria for evaluating participant‐selection strategies for such trials. We argue that the pandemic context—in particular, great urgency to develop safe and effective treatments, uncertainty surrounding Covid‐19, and strain on the health care system that limits the time and effort available for trial enrollment—favors participant‐selection strategies that optimize the ease of enrollment and, ideally, social value. A lottery and, where possible, a weighted lottery have important advantages in these respects.


title: Redesign of a GI endoscopy unit during the COVID-19 emergency: A practical model

text: The pandemic diffusion of the SARS-CoV-2 infection throughout the world required measures to prevent and strategies to control the infection, as well as the reallocation of the hospital structures in order to take care of an increased number of infected patients. Endoscopy Units should be able to perform endoscopic procedures on COVID-19 infected as well as on noninfected patients. The aim of this manuscript is to propose a model for a fast reorganization of the endoscopy department environment in order to safely perform endoscopic procedures in this Pandemic COVID-19 scenario, according to the current advices given by the Scientific Societies


title: Rhinovirus species and clinical features in children hospitalised with pneumonia from Mozambique

text: OBJECTIVES: To describe the prevalence of human rhinovirus (RV) species in children hospitalised with pneumonia in Manhiça, Mozambique, and the associations between RV species and demographic, clinical and laboratory features. METHODS: Nasopharyngeal aspirates were collected from children 0 to 10 years of age (n = 277) presenting to Manhiça District Hospital with clinical pneumonia. Blood samples were collected for HIV and malaria testing, blood culture and full blood counts, and a chest X‐ray was performed. A panel of common respiratory viruses was investigated using two independent multiplex RT‐PCR assays with primers specific for each virus and viral type. RV species and genotypes were identified by seminested PCR assays, sequencing and phylogenetic tree analyses. RESULTS: At least one respiratory virus was identified in 206 (74.4%) children hospitalised with clinical pneumonia. RV was the most common virus identified in both HIV‐infected (17 of 38, 44.7%) and HIV‐uninfected (74 of 237, 31.2%; P = 0.100) children. RV‐A was the most common RV species identified (47 of 275, 17.0%), followed by RV‐C (35/275, 12.6%) and RV‐B (8/275, 2.9%). Clinical presentation of the different RV species was similar and overlapping, with no particular species being associated with specific clinical features. CONCLUSIONS: RV‐A and RV‐C were the most common respiratory viruses identified in children hospitalised with clinical pneumonia in Manhiça. Clinical presentation of RV‐A and RV‐C was similar and overlapping.


The detection of diverse coronaviruses, including MERS-related coronaviruses, in South African bat populations and their associated ecology in Neoromica capensis


title: The Role of MicroRNA in the Airway Surface Liquid Homeostasis

text: Mucociliary clearance, mediated by a coordinated function of cilia bathing in the airway surface liquid (ASL) on the surface of airway epithelium, protects the host from inhaled pathogens and is an essential component of the innate immunity. ASL is composed of the superficial mucus layer and the deeper periciliary liquid. Ion channels, transporters, and pumps coordinate the transcellular and paracellular movement of ions and water to maintain the ASL volume and mucus hydration. microRNA (miRNA) is a class of non-coding, short single-stranded RNA regulating gene expression by post-transcriptional mechanisms. miRNAs have been increasingly recognized as essential regulators of ion channels and transporters responsible for ASL homeostasis. miRNAs also influence the airway host defense. We summarize the most up-to-date information on the role of miRNAs in ASL homeostasis and host–pathogen interactions in the airway and discuss concepts for miRNA-directed therapy.


title: The M Protein of SARS-CoV: Basic Structural and Immunological Properties

text: We studied structural and immunological properties of the SARS-CoV M (membrane) protein, based on comparative analyses of sequence features, phylogenetic investigation, and experimental results. The M protein is predicted to contain a triple-spanning transmembrane (TM) region, a single N-glycosylation site near its N-terminus that is in the exterior of the virion, and a long C-terminal region in the interior. The M protein harbors a higher substitution rate (0.6% correlated to its size) among viral open reading frames (ORFs) from published data. The four substitutions detected in the M protein, which cause non-synonymous changes, can be classified into three types. One of them results in changes of pI (isoelectric point) and charge, affecting antigenicity. The second changes hydrophobicity of the TM region, and the third one relates to hydrophilicity of the interior structure. Phylogenetic tree building based on the variations of the M protein appears to support the non-human origin of SARS-CoV. To investigate its immunogenicity, we synthesized eight oligopeptides covering 69.2% of the entire ORF and screened them by using ELISA (enzyme-linked immunosorbent assay) with sera from SARS patients. The results confirmed our predictions on antigenic sites.


title: Learning during a crisis: The SARS epidemic in Taiwan

text: Abstract SARS struck Taiwan in 2003, causing a national crisis. Many people feared that SARS would spread through the health care system, and outpatient visits fell by more than 30% in the course of a few weeks. We examine how both public information and the behavior and opinions of peers contributed to this reaction. We identify a peer effect through a difference-in-difference comparison of longtime residents and recent arrivals, who are less socially connected. Although several forms of social interaction may contribute to this pattern, social learning is a plausible explanation for our finding. We find that people respond to both public information and to their peers. In a dynamic simulation based on the regressions, social interactions substantially magnify the response to SARS.


title: Jasmonic Acid (JA) Acts as a Signal Molecule in LaCl(3)-Induced Baicalin Synthesis in Scutellaria baicalensis Seedlings

text: Rare earth elements (REEs) have been widely used to increase accumulation of biomass and secondary metabolites in medicinal plants in China. However, very few studies have investigated how REEs mediate secondary metabolism synthesis in medicinal plants. Lanthanum (La), an important REE, is known to improve the accumulation of secondary metabolites in medicinal plants and is widely distributed in China. However, few studies have evaluated the signal transduction leading to La-induced secondary metabolism in medicinal plants. In this study, LaCl(3) treatment-induced multiple responses in Scutellaria baicalensis seedlings, including the rapid generation of jasmonic acid (JA), sequentially followed by the enhancement of baicalin production. Direct application of JA also promoted the synthesis of baicalin in the absence of LaCl(3). LaCl(3)-induced baicalin synthesis was blocked by two different JA synthesis inhibitors. Our results showed that JA acts as a signal component within the signaling system leading to La-induced baicalin synthesis in S. baicalensis seedlings.


title: Structural breaks in international tourism demand: Are they caused by crises or disasters?

text: It is recognised that the tourism industry is vulnerable to some form of crises or disaster. However, despite the attention given to the nature and consequences of tourism crises and disasters, there is a gap in the literature regarding the ex-post detection of these events. In this article, we estimate both the number and date of structural breaks in international tourism arrival series for 25 countries and Madeira Island using the Bai and Perron (1998) structural break test. We compare the date of tourism crises and disasters to the dating of these structural breaks. We observe that tourism crises and disasters are largely consistent with the dates of breaks. Therefore, this method allows us to solve a gap in the tourism industry related to the correct allocation of negative shocks in international tourism arrival demand to crisis or disaster phenomena.


title: Outlook of tourism recovery amid an epidemic: Importance of outbreak control by the government

text: The recent decades have witnessed various epidemics. This year, COVID-19 has severely hit the global tourism industry, especially in destinations that largely depend on tourists from Mainland China. While the government should prioritize the curbing of epidemics, minimal attention has been paid to residents' positive outlook of tourism recovery, which affects public engagement during the recovery stage. Through an online survey conducted with 228 Macao residents in the early phase of epidemic, this study found that residents anticipate quick tourism recovery when they are satisfied with the government's performance in dealing with epidemic, because of their self-efficacy in avoiding infection and government efficacy in tourism recovery, but not relief of emotional concern. Implications for government at destination are also discussed.


title: Toward a Common Secure Future: Four Global Commissions in the Wake of Ebola

text: Lawrence Gostin and colleagues offer a set of priorities for global health preparedness and response for future infectious disease threats.


title: A dystopian vision of China Ma Jian Flora Drew

text: Unknown


2010: The Year of the Lung


title: Positive Correlation Between General Public Knowledge and Attitudes Regarding COVID-19 Outbreak 1 Month After First Cases Reported in Indonesia

text: The increasing number cases of coronavirus disease (COVID-19) infections in the general population in Indonesia raises questions concerning the public’s knowledge and attitudes regarding this pandemic. To determine the correlation between the general public’s knowledge and attitudes regarding the COVID-19 outbreak 1 month after the first cases were reported in Indonesia. This cross-sectional study was conducted between early March and the end of April 2020 in the general population of Indonesia, beginning with the North Sumatra region, where the spread of COVID-19 in Indonesia began. Questionnaires were randomly distributed online in the red zone in Indonesia. Data were collected by collecting people’s responses to the questionnaire, which were distributed via WhatsApp (WA) application and were competed independently by the participants. A descriptive analysis was conducted to describe the demographic characteristics, knowledge, and attitudes of the general population. A total of 201 people had good knowledge (98%) and a positive attitude (96%) regarding the COVID-19 pandemic. The respondents had a negative attitude in relation to two aspects of the COVID-19 outbreak: having to always maintain a distance of 1.5 m when in crowds, and not being able to regularly exercise or eat nutritious food (78.6% and 79.1%, respectively). Most people in Indonesia have good knowledge and a positive attitude regarding the COVID-19 pandemic. However, negative attitudes were still found in this study, and as a result, transmission prevention measures cannot reach their maximum effectiveness by simply publicizing the increase in day-to-day cases to the general public.


Potential Pathophysiology of COVID-19 in Patients with Obesity


title: Spatial Analysis of Global Variability in Covid-19 Burden

text: BACKGROUND: Since the first occurrence of coronavirus disease 2019 (Covid-19), a number of online tools have become available to assist with tracking Covid-19 prevalence. Yet we are unaware of resources that provide country-specific Covid-19 incidence data. METHODS: We undertook a descriptive analysis of the global impact of Covid-19 using data reported on March 17, 2020. The prevalence of Covid-19 cases, fatalities attributed to Covid-19, and the case fatality rate for each of the 238 countries were accessed from the World Health Organization global Covid-19 tracking site, and we additionally calculated Covid-19 incidence based on country-specific population data. We determined the country-specific point prevalence and incidence of Covid-19 and associated deaths while using geocoded data to display their spatial distribution with geographic heat maps. RESULTS: The analysis included 193,197 Covid-19 cases and 7859 associated deaths. The point prevalence was highest in China (80,881), Italy (31,506), Iran (16,169), and Spain (11,312); no other country reported more than 10,000 cases. The incidence (per million population) was highest in San Marino (3389) followed by Iceland (645) and Italy (521); no other country had an incidence above 400 per million population. CONCLUSION: Countries with a high Covid-19 prevalence may not have a high incidence, and vice versa. Public health agencies that provide real-time infection tracking tools should report country-specific Covid-19 incidence metrics, in addition to prevalence data.


title: In vitro and in vivo activity of aurintricarboxylic acid preparations against Cryptosporidium parvum

text: OBJECTIVES: The aim of this study was to assess the effect of commercial aurintricarboxylic acid (ATA) against Cryptosporidium parvum. METHODS: The anticryptosporidial effect of ATA was evaluated in vitro using cell culture and double fluorogenic staining, and in vivo in experimentally infected neonatal C57BL/6 mice. Mice were orally treated for 9 consecutive days starting on the day of infection with daily ATA doses of 50 and 100 µmol/kg. Paromomycin (100 mg/kg) was used as a positive control. RESULTS: In both in vitro models, ATA at concentrations of 100 and 10 µmol/L completely inhibited sporozoites within 10 and 60 min, respectively. Viability of oocysts exposed to 100 µmol/L and assessed by flow cytometry and in cell culture was reduced by 65% and 61%, respectively. The treatment of neonatal mice with a daily ATA dose of 100 µmol/kg led to 97–99% inhibition of infection without any observable negative effects on the animals. In comparison, the mean reduction of infection for paromomycin was 79–84%. CONCLUSIONS: ATA exerted high anticryptosporidial activity and should be considered for further study.


title: Aging and Feeling Valued Versus Expendable During the COVID-19 Pandemic and Beyond: a Review and Commentary of Why Mattering Is Fundamental to the Health and Well-Being of Older Adults

text: The current commentary and review examines the potentially protective role of feelings of mattering among elderly people during typical times and the current atypical times associated with the COVID-19 global pandemic. Mattering is the feeling of being important to others in ways that give people the sense that they are valued and other people care about them. We contrast this feeling with messages of not mattering and being expendable and disposable due to ageism, gaps in the provision of care, and apparently economically focused positions taken during the pandemic that disrespect the value, worth, and merits of older persons. We provide a comprehensive review of past research on individual differences in mattering among older adults and illustrate the unique role of mattering in potentially protecting older adults from mental health problems. Mattering is also discussed in terms of its links with loneliness and physical health. This article concludes with a discussion of initiatives and interventions that can be modified and enhanced to instill a sense of mattering among older adults. Key directions for future research are also highlighted along with ways to expand the mattering concept to more fully understand and appreciate the relevance of mattering among older adults.


title: Guidance for Cardiac Electrophysiology During the Coronavirus (COVID-19) Pandemic from the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; and the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American

text: Abstract Covid-19 is a global pandemic that is wreaking havoc with the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint document from representatives of the HRS, ACC and AHA we identify the potential risks of exposure to patients, allied health care staff, industry representatives and hospital administrators. We describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and non-invasive electrophysiology procedures, clinic visits and cardiac device interrogations. We discuss resource conservation and the role of tele-medicine in remote patient care along with management strategies for affected patients.


title: Efficient replication and shedding of MERS CoV from the upper respiratory tract of experimentally infected dromedary camels

text: The Middle East respiratory syndrome coronavirus (MERS CoV) is a novel coronavirus first recognized in 2012 and is associated with severe respiratory disease in humans. Virus has been isolated from dromedary camels in endemic areas, and many camels also have neutralizing antibodies against the virus, suggesting that they are likely a reservoir host. In order to better understand the role of camels in virus transmission we experimentally infected 3 adult, male dromedary camels with a human isolate of MERS CoV. All animals developed a transient, upper respiratory tract infection associated with very minor clinical disease. Large quantities of infectious virus were isolated from nasal secretions from each animal through 7 days post-inoculation, and viral RNA was detected much longer. Although our study design was limited to 3 animals, these data indicate that MERS CoV readily infects camels, which shed large amounts of virus and likely can efficiently transmit virus to other camels and humans.


title: Adverse Events Associated with High‐Dose Ribavirin: Evidence from the Toronto Outbreak of Severe Acute Respiratory Syndrome

text: Study Objectives. To distinguish adverse events related to ribavirin therapy from those attributable to severe acute respiratory syndrome (SARS), and to determine the rate of potential ribavirin‐related adverse events. Design. Retrospective cohort study. Setting. Hospitals in Toronto, Ontario, Canada. Patients. A cohort of 306 patients with confirmed or probable SARS, 183 of whom received ribavirin and 123 of whom did not, between February 23, 2003, and July 1, 2003. Of the 183 treated patients, 155 (85%) received very high‐dose ribavirin; the other 28 treated patients received lower‐dose regimens. Measurements and Main Results. Data on all patients with SARS admitted to hospitals in Toronto were abstracted from charts and electronic databases onto a standardized form by trained research nurses. Logistic regression was used to evaluate the association between ribavirin use and each adverse event (progressive anemia, hypomagnesemia, hypocalcemia, bradycardia, transaminitis, and hyperamylasemia) after adjusting for SARS‐related prognostic factors and corticosteroid use. In the primary logistic regression analysis, ribavirin use was strongly associated with anemia (odds ratio [OR] 3.0, 99% confidence interval [CI] 1.5–6.1, p<0.0001), hypomagnesemia (OR 21, 99% CI 5.8–73, p<0.0001), and bradycardia (OR 2.3, 99% CI 1.0–5.1, p=0.007). Hypocalcemia, transaminitis, and hyperamylasemia were not associated with ribavirin use. The risk of anemia, hypomagnesemia, and bradycardia attributable to ribavirin use was 27%, 45%, and 17%, respectively. Conclusions. High‐dose ribavirin is associated with a high rate of adverse events. The use of high‐dose ribavirin is appropriate only for the treatment of infectious diseases for which ribavirin has proven clinical efficacy, or in the context of a clinical trial. Ribavirin should not be used empirically for the treatment of viral syndromes of unknown origin.


title: Adoption of telemedicine services by substance abuse treatment facilities in the U.S.

text: OBJECTIVE: To describe trends in licensed substance use treatment facilities' adoption of telemedicine and how adoption varies across local factors, including county-level drug overdose rates, urbanicity measures, and state policy laws. METHODS: We analyzed data (2016–2019) from the National Directory of Drug and Alcohol Abuse Treatment Facilities. Our main outcome was telemedicine use by a treatment facility. We also captured independent variables from other datasets, including estimated county-level drug poisoning deaths and state-level telemedicine policies. We estimated a multivariable logistic regression model to determine which facility characteristics were associated with offering telemedicine. RESULTS: From 2016 to 2019, an average of 12,334 treatment facilities were included. During this period, the unadjusted proportion of facilities offering telemedicine grew from 13.5% to 17.4% (p < 0.001). In adjusted models, rural location; offering multiple treatment settings; offering pharmacotherapy; and serving both adult and pediatric patients were associated with greater telemedicine adoption (p < 0.05 for all comparisons). DISCUSSION: Use of telemedicine is increasing steadily among substance use disorder (SUD) treatment facilities; however, uptake is uneven and relatively low. As such, telemedicine may be an underutilized tool to expand access to care for patients with SUDs.


title: Past, present and future: experiences and lessons from telehealth projects

text: Information communications technology has been a focus of the work of the International Development Research Centre (IDRC) since 1970, when this organization was formed in Canada with the goal of helping to improve the health of people in developing countries (http://www.idrc.ca). In this article, we focus on the field of telemedicine in developing countries and its role in improving health, using examples from the experience of the IDRC.


title: NBCZone: Universal three-dimensional construction of eleven amino acids near the catalytic nucleophile and base in the superfamily of (chymo)trypsin-like serine fold proteases

text: Abstract (Chymo)trypsin-like serine fold proteases belong to the serine/cysteine proteases found in eukaryotes, prokaryotes, and viruses. Their catalytic activity is carried out using a triad of amino acids, a nucleophile, a base, and an acid. For this superfamily of proteases, we propose the existence of a universal 3D structure comprising 11 amino acids near the catalytic nucleophile and base – Nucleophile-Base Catalytic Zone (NBCZone). The comparison of NBCZones among 169 eukaryotic, prokaryotic, and viral (chymo)trypsin-like proteases suggested the existence of 15 distinct groups determined by the combination of amino acids located at two “key” structure-functional positions 54T and 55T near the catalytic base His57T. Most eukaryotic and prokaryotic proteases fell into two major groups, [ST]A and TN. Usually, proteases of [ST]A group contain a disulfide bond between cysteines Cys42T and Cys58T of the NBCZone. In contrast, viral proteases were distributed among seven groups, and lack this disulfide bond. Furthermore, only the [ST]A group of eukaryotic proteases contains glycine at position 43T, which is instrumental for activation of these enzymes. In contrast, due to the side chains of residues at position 43T prokaryotic and viral proteases do not have the ability to carry out the structural transition of the eukaryotic zymogen-zyme type.


Providing care for pediatric cancer patients in the COVID‐19 era: Rapid response recommendations from a developing country


title: p53- and ROS-mediated AIF pathway involved in TGEV-induced apoptosis

text: We previously demonstrated that transmissible gastroenteritis virus (TGEV) could induce apoptosis through caspase signaling. However, apoptosis was not completely prevented by caspases inhibitors, suggesting that there may be a caspase-independent pathway involved in TGEV-induced cell apoptosis. In this study, we investigated the regulation of apoptosis-inducing factor (AIF) on TGEV-induced apoptotic pathway. Results indicated that AIF translocated from the mitochondria to nucleus during TGEV infection, and the AIF inhibitor, N-phenylmaleimide (NP), significantly attenuated the apoptosis. In addition, the translocation of AIF was inhibited by Veliparib (ABT-888), an inhibitor of poly (ADP-ribose) polymerase (PARP). And the reactive oxygen species (ROS) scavenger, pyrrolidinedithiocarbamic (PDTC), redistributed AIF in the mitochondria and nucleus in TGEV-infected cells. Moreover, the protein levels in nucleus and the mRNA levels of AIF were inhibited in the presence of the p53 inhibitor, piﬁthrin-α (PFT-α) or in TGEV-infected p53−/−cells. Furthermore, TGEV-induced apoptosis was blocked by combination of three or more inhibitors, such as pan caspase inhibitor Z-VAD-FMK, NP, ABT-888, PDTC, PFT-α, to treat PK-15 cells. Taken together, these results suggest that the p53- and ROS-mediated AIF pathway and caspase-dependent pathway were involved in TGEV-induced apoptosis.


title: Pyrexia in juvenile dogs: a review of 140 referred cases

text: OBJECTIVES: To describe the presentation, influence of previous treatment and diagnosis in juvenile dogs presenting with pyrexia to a UK referral centre. MATERIALS AND METHODS: Clinical records of dogs aged 1 to 18 months presenting with a problem list including pyrexia (≥⃒39∙2°C) that was reproducible during referral hospitalisation were retrospectively reviewed. Signalment, history ‐ including previous treatment, clinical examination findings and diagnosis were recorded. Diagnoses were categorised as non‐infectious inflammatory, infectious, congenital, neoplastic and miscellaneous. The influence of previous treatment on the ability to reach a final diagnosis was analysed. RESULTS: A total of 140 cases was identified. Diagnosis was reached in 115 cases. Non‐infectious inflammatory disease was identified in 91 cases (79%), infectious disease in 19 cases (17%), a congenital disorder in four dogs (3%) and neoplasia in one dog (1%). Breeds most commonly identified were Border collies (17/140; 12%), beagles (16/140; 11%), Labrador retrievers (11/140; 8%), springer spaniels (9/140; 6%) and cocker spaniels (8/140; 6%). Before presentation, most dogs had received antibiotics (83/140; 59%), non‐steroidal anti‐inflammatory drugs (84/140; 60%) or steroids (9/140; 6%), either alone or in combination. Neither antibiotics nor non‐steroidal anti‐inflammatory drugs influenced the ability to reach a diagnosis. Steroid‐responsive meningitis‐arteritis comprised 55 of 91 (60%) individuals of the non‐infectious inflammatory cohort. All four dogs diagnosed with congenital disorders were Border collies. CLINICAL SIGNIFICANCE: Non‐infectious inflammatory disease, particularly steroid‐responsive meningitis‐arteritis, immune‐mediated polyarthritis and metaphyseal osteopathy, was commonly diagnosed in this population of pyrexic juvenile dogs.


Hydroxychloroquine: A Familiar Agent to Combat the Pandemic of COVID-19


title: Peer support — A secret weapon in the fight against COVID‐19

text: Peer supporters are proving to be invaluable, providing connection and hope during this unprecedented time. As orders restricting movement challenged traditional service delivery practices, peer supporters kicked into high gear doing what they do: breaking isolation, engaging clients and modeling recovery.


title: Infectogenomics: Insights from the Host Genome into Infectious Diseases

text: Five years into the human postgenomic era, we are gaining considerable knowledge about host-pathogen interactions through host genomes. This “infectogenomics” approach should yield further insights into both diagnostic and therapeutic advances, as well as normal cellular function.


title: Feline Morbillivirus, a New Paramyxovirus Possibly Associated with Feline Kidney Disease

text: Feline morbillivirus (FeMV) was first isolated in stray cats in Hong Kong in 2012. Since its discovery, the virus has been reported in domestic cats worldwide, including in Hong Kong, Japan, Italy, US, Brazil, Turkey, UK, Germany, and Malaysia. FeMV is classified in the Morbillivirus genus within the Paramyxoviridae family. FeMV research has focused primarily on determining the host range, symptoms, and characteristics of persistent infections in vitro. Importantly, there is a potential association between FeMV infection and feline kidney diseases, such as tubulointerstitial nephritis (TIN) and chronic kidney diseases (CKD), which are known to significantly affect feline health and survival. However, the tropism and viral entry mechanism(s) of FeMV remain unknown. In this review, we summarize the FeMV studies up to date, including the discoveries of various FeMV strains, basic virology, pathogenicity, and disease signs.


title: NUEVOS VIRUS RESPIRATORIOS EN PEDIATRÍA

text: RESUMEN Las infecciones respiratorias continúan siendo la mayor causa de morbimortalidad en pediatría. Los virus constituyen los agentes infecciosos más frecuentes, actualmente con los avances en las técnicas diagnósticas se han sumado “nuevos virus” entre los que destacan Metapneumovirus (MPVh), Bocavirus (BoVh) y Coronavirus (CoVh), que son el objetivo de este artículo. SUMMARY Acute lower respiratory infection is still the leading cause of global morbility and mortality in children. Viruses are the most frequent pathogen, currently the most common viral etiology VRS, although recently due to advances in diagnostic techniques new viruses have been added, that includes Metapneumovirus (hMPV), Bocavirus (hBoV) and Coronavirus (hCoV), which are the purpose of this review.


title: An investigation of the combined effect of an annual mass gathering event and seasonal infectiousness on disease outbreak

text: Abstract In this paper, we investigate the effects of recurring mass gathering event on the spread of an epidemic. Mass gatherings take place when a large number of people from different locations visit a particular region during a short time period. Such activity plays a crucial role in the epidemic spread as traveling facilitates the spread of an epidemic between disparate locations and crowded conditions can accelerate the disease transmission. An additional component that affects disease spread is the seasonality in transmission. In this paper, we study the interplay between the periodic natures of seasonal transmission and of an annual mass gathering event. We find that the timing of the gathering relative to the peak in transmissibility can have a profound impact on the likelihood of an outbreak.


title: Qu’apprend-t-on de nouveau des épidémies émergentes ?

text: Points essentiels L’Afrique et l’Asie du Sud-Est sont les épicentres des maladies infectieuses émergentes et des scénarios de menace épidémique menaçant les mégapoles de densité humaine élevée. La mobilité massive et les réticences des populations exposées au risque de maladies infectieuses épidémiques, associées à un système de santé fragile sont les facteurs limitants le déploiement de l’alerte et le contrôle de leur émergence et de leur extension géographique. La détection et la persistance d’un agent viral dans le fluide séminal sont de mise pour des raisons cliniques et de santé publique, chez le patient convalescent d’une infection causée par un virus émergent à propension épidémique ou menaçante. Les structures de prise en charge des patients atteints de maladies infectieuses par agent hautement pathogène sur le terrain épidémique font l’objet de progrès innovants en matière d’architecture pour limiter le risque d’exposition au risque infectieux et améliorer l’ergonomie des professionnels de santé dédiés, et dans la perspective d’une densification de l’offre de soin de support sans poser de nouvelles contraintes au personnel dans l’exercice du soin. Malgré de multiples défis et en premier éthiques et opérationnels à relever, il est nécessaire de déployer une activité de recherche clinique au cours des urgences épidémiques, et les produits candidats diagnostiques, thérapeutiques ou de prévention prometteurs doivent faire l’objet d’essais d’évaluation rigoureux. Les programmes multidisciplinaires de préparation et d’anticipation, y compris en vue de la gestion des crises humanitaires complexes avec scénario de résistance ou de défiance de la part des communautés affectées, constituent la base de la riposte aux épidémies de maladies infectieuses émergentes à risque menaçant et imposent le renforcement des infrastructures d’intervention de santé publique et des systèmes d’alerte épidémique dans les régions à haut risque. Key points Africa along side with south-east Asia are the epicentres of emerging and epidemic prone-infectious diseases and megacity biosecurity threat scenarios. Massive mobility and reluctance in the populations exposed to epidemic and emerging prone-infectious diseases coupled by a weak health system made disease alert and control measures difficult to implement. The investigation of virus detection and persistence in semen across a range of emerging viruses is useful for clinical and public health reasons, in particular for viruses that lead to high mortality or morbidity rates or to epidemics. Innovating built facility to safely treat patients with highly pathogenic infectious diseases is urgently need, not only to prevent the spread of infection from patients to healthcare workers but also to offer provision of relatively invasive organ support, whenever considered appropriate, without posing additional risk to staff. Despite multiple challenges, the need to conduct research during epidemics is inevitable, and candidate products must continue undergoing rigorous trials. Preparedness including management of complex humanitarian crises with community distrust is a cornerstone in response to high consequence emerging infectious disease outbreaks and imposes strengthening of the public health response infrastructure and emergency outbreak systems in high-risk regions.


title: Diffusion size and structural virality: The effects of message and network features on spreading health information on twitter

text: Abstract Relying on diffusion of innovation theory, this study examines the impacts of perceived message features and network characteristics on size (i.e., the number of retweets a message receives) and structural virality (i.e., quantified distinction between broadcast and viral diffusion) of information diffusion on Twitter. The study collected 425 unique tweets posted by CDC during a 17-week period and constructed a diffusion tree for each unique tweet. Findings indicated that, with respect to message features, perceived efficacy after reading a tweet positively predicted diffusion size of the tweet, whereas perceived susceptibility to a health condition after reading a tweet positively predicted structural virality of the tweet. Perceived negative emotion positively predicted both size and structural virality. With respect to network features, the level of involvement of brokers in diffusing a tweet increased the tweet's structural virality. Theoretical and practical implications were discussed on disseminating health information via broadcasting and viral diffusion on social media.


COVID 19 CRISIS: Maintaining Brachytherapy Access and Strategies For Risk Mitigation


title: Chapter 3 Structure and Working of Viral Fusion Machinery

text: Publisher Summary This chapter discusses the structure and working of viral fusion machinery. The entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Structural studies have defined three classes of viral membrane fusion proteins. Despite their different structural organizations, all seem to have a common mechanism of action that generates the same lipid organizations during the fusion pathway. The entry of enveloped viruses into host cells requires binding of the virus to one or more receptors present at the cell surface, followed by fusion of the viral envelope with a cellular membrane. These steps are mediated by virally encoded glycoproteins that promote both receptor recognition and membrane fusion. The first crystal structure of a viral fusion protein ectodomain that has been determined is that of influenza virus hemagglutinin (HA) in its prefusion conformation. The structures of viral fusion glycoproteins, of which the conformational change is triggered at low pH, has allowed the identification of amino acid residues that play the role of pH-sensitive molecular switches.


title: Population implications of cessation of IVF during the COVID-19 pandemic

text: RESEARCH QUESTION: Discontinuation of in vitro fertilisation (IVF) cycles has been part of the radical transformation of healthcare provision to enable reallocation of staff and resources to deal with the COVID-19 pandemic. We sought to estimate the impact of cessation of treatment on individual prognosis and United States population live-birth rates. DESIGN: Data from 271,438 ovarian stimulation UK IVF cycles was used to model the effect of age as a continuous, yet non-linear, function on cumulative live-birth rate. We recalibrated this model to cumulative live-birth rates reported for the 135,6733 stimulation cycles undertaken in the USA in 2016, with live-birth follow-up to October 2018. We calculated the effect of a one-month, three-month and six-month shutdown in IVF treatment as the effect of the equivalent increase in a woman's age, stratified by age group. RESULTS: The average reduction in cumulative live-birth rate would be 0.3% [95% CI: 0.3, 0.3], 0.8% [0.8, 0.8] and 1.6% [1.6, 1.6] for a one-month, three-month and six-month shutdown, respectively. This corresponds to a reduction of 369 [95% CI; 360, 378), 1,098 [1071, 1123] and 2,166 [2,116, 2,216] live-births in the cohort, respectively. The greatest contribution to this reduction was from older mothers. CONCLUSIONS: We demonstrate that the discontinuation of fertility treatment for even 1 month in the USA could result in 369 fewer women having a live-birth, due to the increase in patients’ age during the shutdown. As a result of reductions in cumulative live-birth rate, more cycles may be required to overcome infertility at an individual and population level.Introduction


title: In vitro evidence of cellular adaptation to ozone toxicity in the rat trachea

text: Abstract Adaptation to prolonged ozone (O3) exposure occurs in the tracheal epithelium of rats and is marked by the presence of ciliated cells with uniform short cilia but is not accompanied by shifts in cell populations, altered characteristics of epithelial secretory cell products, increased cell turnover, or elevated tracheal superoxide dismutase activity. The purpose of this study was to test the hypothesis that adaptation is a result of alterations intrinsic to epithelial cells or to the cells and their matrix, and not due to systemic or neural influences. Rats were preexposed to either filtered air (FA) or 0.96 ppm O3 for 8 hr/night for 60 days, and then their tracheae were removed and exposed to 3 ppm O3 in an explant culture system where behavioral, nasal, exudative, and secretory product influences can be eliminated. After exposure to 3 ppm O3 in vitro, quantitative electron microscopic evaluation demonstrated that the epithelia from the FA preexposure group had significantly more necrotic cells and sloughed cells and fewer ciliated cells than the epithelia from the O3 preexposure group. Thus previous exposure to ozone in vivo induces a change in tracheal epithelium which confers resistance to ozone-induced injury in the explant exposure system.


title: Cryptosporidium and concurrent infections with other major enterophatogens in 1 to 30-day-old diarrheic dairy calves in central Spain

text: Abstract Faeces samples from 218, 1 to 30-day-old, diarrheic dairy calves in 65 dairy herds were screened for the presence of Cryptosporidium and concurrent infections with rotavirus, coronavirus, F5+ Escherichia coli and Salmonella spp. Calves were grouped according to their age as follows: 1–7, 8–14, 15–21 and 22–30 days. Cryptosporidium infection was detected in 43.8%, 71.9%, 63.2% and 6.9% of the calves in the respective age groups. Significant differences in the detection rate of Cryptosporidium were found between the age group 22–30 days and all other age groups, and between the age group 1–7 days and the age groups 8–14 days and 15–21 days. Cryptosporidium was the only enteropathogen detected in 60 of the 114 (52.6%) diarrheic calves. Concurrent infections with other enteropathogen(s) were detected in 64.3%, 46.3%, 39.5% and 0% of the Cryptosporidium-infected calves in the age groups 1–7, 8–14, 15–21 and 22–30 days, respectively. A significant age-associated decrease in the detection rate of mixed infections (p <0.05) was found. The detection rates of the other enteropathogens considered in calves with Cryptosporidium infection were 87% for rotavirus, 11.1% for coronavirus, 27.8% for F5+ E. coli and 1.8% for Salmonella.


title: China hotel research: A systematic review of the English language academic literature

text: Abstract This paper presents the findings of a systematic review performed on 115 academic papers published over a 26-year period from 1984 to 2009 and provides a content analysis of research themes and trends in China hotel research. The findings reveal that hotel management and performance is the theme most frequently examined by researchers, followed by hotel development strategies, and hotel business environment analysis. The analysis also indicates shifts in research methods, trends of publication, journal outlets and authorship information.


The JPC-SE Position Statement on Asbestos: A Long-Overdue Appeal by Epidemiologists to Ban Asbestos Worldwide and End Related Global Environmental Injustice


title: Activities of proteasome and m-calpain are essential for Chikungunya virus replication

text: Replication of many viruses is dependent on the ubiquitin proteasome system. The present study demonstrates that Chikungunya virus replication increases proteasome activity and induces unfolded protein response (UPR) in cultured cells. Further, it was seen that the virus replication was dependent on the activities of proteasomes and m-calpain. Proteasome inhibition induced accumulation of polyubiquitinated proteins and earlier visualization of UPR.


title: Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks

text: A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein–DNA interactions, posttranslational protein modifications (PTMs), lectin–glycan recognition, pathogen–host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier.


title: The impact of the COVID-19 pandemic on the mental health of healthcare professionals

text: INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs’ distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.


Protecting workers aged 60–69 years from COVID-19


title: Engineered unnatural ubiquitin for optimal detection of deubiquitinating enzymes

text: Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin (Ub) from its protein conjugates. DUBs have been implicated as attractive therapeutic targets in the treatment of viral diseases, neurodegenerative disorders and cancer. The lack of selective chemical tools for the exploration of these enzymes significantly impairs the determination of their roles in both normal and pathological states. Commercially available fluorogenic substrates are based on the C-terminal Ub motif or contain Ub coupled to a fluorophore (Z-LRGG-AMC, Ub-AMC); therefore, these substrates suffer from lack of selectivity. By using a hybrid combinatorial substrate library (HyCoSuL) and a defined P2 library containing a wide variety of nonproteinogenic amino acids, we established a full substrate specificity profile for two DUBs—MERS PLpro and human UCH-L3. Based on these results, we designed and synthesized Ub-based substrates and activity-based probes (ABPs) containing selected unnatural amino acids located in the C-terminal Ub motif. Biochemical analysis and cell-based experiments confirmed the activity and selectivity of engineered Ub-based substrates and probes. Using this approach, we propose that for any protease that recognizes Ub and Ub-like substrates, a highly active and selective unnatural substrate or probe can be engineered.


title: Differential production of proinflammatory cytokines in the pig lung during different respiratory virus infections: correlations with pathogenicity

text: Abstract The acute stages of infection with swine influenza virus ( SIV ), porcine respiratory coronavirus ( PRCV ) and porcine reproductive-respiratory syndrome virus ( PRRSV ) were shown to differ in terms of clinical and lung inflammatory effects and proinflammatory cytokine profiles in bronchoalveolar lavage ( BAL ) fluids. Caesarian-derived colostrum-deprived pigs were inoculated intratracheally with one of the three viruses. SIV infection was followed within 1 day post inoculation (d PI ) by characteristic respiratory and general signs, and excessive lung epithelial desquamation and neutrophil infiltration (38 to 56 per cent of BAL cells at 1 d PI vs 0 to 1 per cent in controls). High concentrations of bioactive interferon-α ( IFN -α), tumour necrosis factor-α ( TNF -α) and interleukin-1 ( IL -1) coincided with peak symptoms and neutrophil infiltration. PRCV infection was asymptomatic and produced a mild bronchointerstitial pneumonitis and neutrophil infiltration (13 to 22 per cent of BAL cells at 4 d PI ). IFN -α titres parallelled those found during SIV infection, TNF -α was negligible and IL -1 undetectable. PRRSV infection induced anorexia and lethargy between 3 and 5 d PI . There was marked infiltration with mononuclear cells in alveolar septa and BAL fluids between 7 and 10 d PI , while neutrophils remained at less than 11 per cent of BAL cells at any time. IL -1 was produced from three throughout 10 d PI , while IFN -α production was minimal and TNF -α undetectable. These data strongly suggest that proinflammatory cytokines can be important mediators of viral respiratory disease.


title: Inactivation of severe acute respiratory syndrome coronavirus 2 in plasma and platelet products using a riboflavin and ultraviolet light‐based photochemical treatment

text: BACKGROUND AND OBJECTIVE: Severe acute respiratory distress syndrome coronavirus‐2 (SARS‐CoV‐2), the causative agent of coronavirus disease 2019 (COVID‐19), is a member of the coronavirus family. Coronavirus infections in humans are typically associated with respiratory illnesses; however, viral RNA has been isolated in serum from infected patients. Coronaviruses have been identified as a potential low‐risk threat to blood safety. The Mirasol Pathogen Reduction Technology (PRT) System utilizes riboflavin and ultraviolet (UV) light to render blood‐borne pathogens noninfectious, while maintaining blood product quality. Here, we report on the efficacy of riboflavin and UV light against the pandemic virus SARS‐CoV‐2 when tested in both plasma and platelets units. MATERIALS AND METHODS: Stock SARS‐CoV‐2 was grown in Vero cells and inoculated into either plasma or platelet units. Those units were then treated with riboflavin and UV light. The infectious titres of SARS‐CoV‐2 were determined by plaque assay using Vero cells. A total of five (n = 5) plasma and three (n = 3) platelet products were evaluated in this study. RESULTS: In both experiments, the measured titre of SARS‐CoV‐2 was below the limit of detection following treatment with riboflavin and UV light. The mean log reductions in the viral titres were ≥3·40 and ≥4·53 for the plasma units and platelet units, respectively. CONCLUSION: Riboflavin and UV light effectively reduced the titre of SARS‐CoV‐2 in both plasma and platelet products to below the limit of detection in tissue culture. The data suggest that the process would be effective in reducing the theoretical risk of transfusion transmitted SARS‐CoV‐2.


title: The Facemask in Public and Healthcare Workers– A Need not a Belief

text: Abstract Since the declaration of the COVID-19 pandemic, a lot of data has invaded our lives, and the conflicting findings have caused us to be frantic about the correct course action. Strict isolation and social distancing measures can flatten the coronavirus infectious curve, and the use of facemask needs to be encouraged and facilitated in crowded places, particularly in hospitals where the 6-feet social distancing cannot be adopted because of physical barriers.


title: Chapter 9 Diseases of Free-Ranging Snow Leopards and Primary Prey Species

text: Abstract Although a wide range of diseases have been reported in captive snow leopards, little is known about those affecting the species in the wild. However, the potential threat from diseases to wild snow leopards must not be underestimated as a consequence of lack of health surveillance throughout the inaccessible terrains they occupy. As a felid, the snow leopard is likely to be susceptible to most infectious agents affecting the domestic cat, and here we provide an overview of those with a risk of lethality for free-ranging snow leopards. In contrast to the health of snow leopards themselves, a great deal is known about the diseases affecting their primary prey species. We present these cases and highlight the importance of livestock as the main source of disease spillover to natural prey species. Further studies are required to understand the impact of infectious agents on intra- and interspecific population dynamics of snow leopards and associated prey.


FuelCell Energy announces temporary plant closure regarding COVID-19


title: Identification of a new region of SARS-CoV S protein critical for viral entry

text: Infection by SARS-CoV is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using an HIV-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217–234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (hACE2) in a dose dependent manner (IC50 ~11 µM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A and N232A), and reduced viral entry (L224A, L226A, I228A, T231A and F233A). Taken together, these results reveal a new region of S protein that is crucial for SARS-CoV entry.


title: Long-term analysis of feline calicivirus prevalence and viral shedding patterns in naturally infected colonies of domestic cats

text: Abstract Feline calicivirus (FCV) is a highly infectious respiratory pathogen of domestic cats. The prevalence of FCV in the general cat population is high, particularly in multi-cat households, largely because many clinically recovered cats remain persistently infected carriers. In order to assess how FCV circulates in such groups and to assess the contribution that each individual animal makes to the epidemiology of the disease, we have carried out the first detailed analysis of long-term shedding patterns of FCV in individual cats within naturally infected colonies. The prevalence of FCV in each of the groups on individual sampling occasions ranged from 0% to 91%, with averages for the individual colonies ranging from 6% to 75%. Within each of the colonies, one to three distinct strains of FCV were identified. Individual cats showed a spectrum of FCV shedding patterns over the sampling period which broadly grouped into three categories: those that shed virus relatively consistently, those that shed virus intermittently, and those that appeared never to shed virus. This is the first report identifying non-shedder cats that appear resistant to FCV infection over long periods of time, despite being continually exposed to virus. Such resistance appeared to be age related, which may have been immune-mediated, although by analogy with other caliciviruses, factors such as host genetic resistance may play a role. Given that a proportion of the population appears to be resistant to infection, clearly the cohort of cats that consistently shed virus are likely to provide an important mechanism whereby infection can be maintained in small populations.


China, Africa, and US academia join hands to advance global health


Außer Kontrolle: Regionale Einflüsse auf Gesundheit und Ergebnisse


title: Viral Etiologies of Hospitalized Acute Lower Respiratory Infection Patients in China, 2009-2013

text: BACKGROUND: Acute lower respiratory infections (ALRIs) are an important cause of acute illnesses and mortality worldwide and in China. However, a large-scale study on the prevalence of viral infections across multiple provinces and seasons has not been previously reported from China. Here, we aimed to identify the viral etiologies associated with ALRIs from 22 Chinese provinces. METHODS AND FINDINGS: Active surveillance for hospitalized ALRI patients in 108 sentinel hospitals in 24 provinces of China was conducted from January 2009-September 2013. We enrolled hospitalized all-age patients with ALRI, and collected respiratory specimens, blood or serum collected for diagnostic testing for respiratory syncytial virus (RSV), human influenza virus, adenoviruses (ADV), human parainfluenza virus (PIV), human metapneumovirus (hMPV), human coronavirus (hCoV) and human bocavirus (hBoV). We included 28,369 ALRI patients from 81 (of the 108) sentinel hospitals in 22 (of the 24) provinces, and 10,387 (36.6%) were positive for at least one etiology. The most frequently detected virus was RSV (9.9%), followed by influenza (6.6%), PIV (4.8%), ADV (3.4%), hBoV (1.9), hMPV (1.5%) and hCoV (1.4%). Co-detections were found in 7.2% of patients. RSV was the most common etiology (17.0%) in young children aged <2 years. Influenza viruses were the main cause of the ALRIs in adults and elderly. PIV, hBoV, hMPV and ADV infections were more frequent in children, while hCoV infection was distributed evenly in all-age. There were clear seasonal peaks for RSV, influenza, PIV, hBoV and hMPV infections. CONCLUSIONS: Our findings could serve as robust evidence for public health authorities in drawing up further plans to prevent and control ALRIs associated with viral pathogens. RSV is common in young children and prevention measures could have large public health impact. Influenza was most common in adults and influenza vaccination should be implemented on a wider scale in China.


Teaching empathy and resilience to undergraduate nursing students: A call to action in the context of Covid-19


title: Rules for the recognition of dilysine retrieval motifs by coatomer

text: Cytoplasmic dilysine motifs on transmembrane proteins are captured by coatomer α-COP and β′-COP subunits and packaged into COPI-coated vesicles for Golgi-to-ER retrieval. Numerous ER/Golgi proteins contain K(x)Kxx motifs, but the rules for their recognition are unclear. We present crystal structures of α-COP and β′-COP bound to a series of naturally occurring retrieval motifs—encompassing KKxx, KxKxx and non-canonical RKxx and viral KxHxx sequences. Binding experiments show that α-COP and β′-COP have generally the same specificity for KKxx and KxKxx, but only β′-COP recognizes the RKxx signal. Dilysine motif recognition involves lysine side-chain interactions with two acidic patches. Surprisingly, however, KKxx and KxKxx motifs bind differently, with their lysine residues transposed at the binding patches. We derive rules for retrieval motif recognition from key structural features: the reversed binding modes, the recognition of the C-terminal carboxylate group which enforces lysine positional context, and the tolerance of the acidic patches for non-lysine residues.


title: What do studies in wild mammals tell us about human emerging viral diseases in Mexico?

text: Multiple species of viruses circulate in wild mammals, some of them potentially causing zoonosis. Most of the suspected viral zoonotic diseases affecting human patients remain unidentified with regard to their aetiological agent. The aim of this study is to summarize the state of knowledge of the viral richness associated with wild mammals in Mexico throughout 1900–2018 and their relationship with human cases. We compiled two databases, one of them containing all available published studies on potentially zoonotic viruses in wild mammals and another with human cases related to zoonotic viruses. The database on wild mammals covers the period of 1900–2018; the human case database spans 2000–2013. We calculated the richness of viral potential zoonotic agents and evaluated their geographical distribution. We found 262 records of 42 potential zoonotic viral species associated with 92 wild mammal species in 28 states across Mexico. Records of human viral cases were only found in 29 states, which did not overlap with the reports in wild mammals. We detected 25.6% (42/164) of viral zoonotic agents reported worldwide. This analysis opens a relevant topic of discussion for public health attention.


title: Influenza virus and factors that are associated with ICU admission, pulmonary co-infections and ICU mortality

text: Abstract Purpose While most influenza patients have a self-limited respiratory illness, 5–10% of hospitalized patients develop severe disease requiring ICU admission. The aim of this study was to identify influenza-specific factors associated with ICU admission and mortality. Furthermore, influenza-specific pulmonary bacterial, fungal and viral co-infections were investigated. Methods 199 influenza patients, admitted to two academic hospitals in the Netherlands between 01-10-2015 and 01-04-2016 were investigated of which 45/199 were admitted to the ICU. Results A history of Obstructive/Central Sleep Apnea Syndrome, myocardial infarction, dyspnea, influenza type A, BMI > 30, the development of renal failure and bacterial and fungal co-infections, were observed more frequently in patients who were admitted to the ICU, compared with patients at the normal ward. Co-infections were evident in 55.6% of ICU-admitted patients, compared with 20.1% of patients at the normal ward, mainly caused by Staphylococcus aureus, Streptococcus pneumoniae, and Aspergillus fumigatus. Non-survivors suffered from diabetes mellitus and (pre-existent) renal failure more often. Conclusions The current study indicates that a history of OSAS/CSAS, myocardial infarction and BMI > 30 might be related to ICU admission in influenza patients. Second, ICU patients develop more pulmonary co-infections. Last, (pre-existent) renal failure and diabetes mellitus are more often observed in non-survivors.


title: Phage display for identifying peptides that bind the spike protein of transmissible gastroenteritis virus and possess diagnostic potential

text: The spike (S) protein of porcine transmissible gastroenteritis virus (TGEV) is located within the viral envelope and is the only structural protein that possesses epitopes capable of inducing virus-neutralizing antibodies. Among the four N-terminal antigenic sites A, B, C, and D, site A and to a lesser extent site D (S-AD) induce key neutralizing antibodies. Recently, we expressed S-AD (rS-AD) in recombinant form. In the current study, we used the rS-AD as an immobilized target to identify peptides from a phage-display library with application for diagnosis. Among the 9 phages selected that specifically bound to rS-AD, the phage bearing the peptide TLNMHLFPFHTG bound with the highest affinity and was subsequently used to develop a phage-based ELISA for TGEV. When compared with conventional antibody-based ELISA, phage-mediated ELISA was more sensitive; however, it did not perform better than semi-quantitative RT-PCR, though phage-mediated ELISA was quicker and easier to set up.


Personal protective equipment during the COVID‐19 pandemic: a comment


title: Proteolytic processing of polyproteins 1a and 1ab between non-structural proteins 10 and 11/12 of Coronavirus infectious bronchitis virus is dispensable for viral replication in cultured cells

text: Abstract Coronavirus 3C-like proteinase (3CLpro) plays important roles in viral life cycle through extensive processing of the polyproteins 1a and 1ab into 12 mature, non-structural proteins (nsp5–nsp16). Structural and biochemical studies have revealed that all confirmed 3CLpro cleavage sites have a conserved Gln residue at the P1 position, which is thought to be absolutely required for efficient cleavage. Recent studies on murine hepatitis virus (MHV) showed that processing of the 1a polyprotein at the position between nsp10–nsp11 is essential for viral replication. In this report, we investigated the requirement of processing at the equivalent position for replication of avian coronavirus infectious bronchitis virus (IBV), using an infectious cloning system. The results showed that mutation of the P1 Gln to Pro or deletion of the Gln residue in the nsp10–nsp11/12 site completely abolished the 3CLpro-mediated processing, but allowed production of infectious recombinant viruses with variable degrees of growth defect, suggesting that cleavage at the nsp10–nsp11/12 site of IBV is dispensable for viral replication in cultured cells. This study would pave a way for potential vaccine development by generation of attenuated IBV from field isolates through manipulation of the nsp10–nsp11/12 cleavage site. Similar approaches would be also applicable to other human and animal coronaviruses.


title: Reversible and cachexia‐associated feline skin fragility syndrome in three cats

text: BACKGROUND: Feline skin fragility syndrome (FSFS) is an acquired disorder characterized by altered collagen production resulting in an extremely thin and fragile skin. FSFS is associated with diseases characterized by excessive steroidal hormones that can inhibit collagen synthesis. It is also described concomitantly with severe inflammatory, infectious or neoplastic conditions where the pathogenesis remains largely unknown. OBJECTIVES: To describe three cases of FSFS in cats that become cachectic secondary to different causes without glucocorticoid involvement. To describe the histopathological features of connective tissue for both fragile skin and the skin after healing. RESULTS: All cats developed cachexia in less than two months (body condition score ranging from 1–1.5). Concomitant diseases were diagnosed in Case 1 (aspiration pneumonia due to mega‐oesophagus) and Case 2 (feline immunodeficiency virus (FIV)). In Case 3, malnutrition was suspected as a primary cause. The main histological feature of fragile skin was an atrophic dermis with pale eosinophilic, thin and irregular collagen fibres with numerous red cores observed with Masson's stain. Elastic fibres were normal. Postrecovery histopathological findings at 11 (Case 1) and six months (Case 3) after diagnosis, indicated normalization of the collagen and of the whole skin as compared with controls. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors’ knowledge, this is the first report describing a reversible, nonsteroid‐induced FSFS, associated with rapidly developing cachexia in cats.


title: Off‐Label Therapies for COVID‐19—Are We All In This Together?

text: SARS-CoV-2 continues to spread rapidly outside of mainland China. As of April 6, there are over 300,000 cases and 10,000 deaths in the US. Effective therapies for the novel Coronavirus are urgently needed and over 200 clinical trials are now underway across the globe. Recognizing the need for robust randomized control trials, the World Health Organization (WHO) recently organized a multinational randomized trial-the SOLIDARITY trial-to study the effect of drugs that have been identified as promising based on in-vitro data and the early clinical experience with COVID-19: Remdesivir, lopinavir and ritonavir; lopinavir and ritonavir + interferon; and chloroquine or hydroxychloroquine.


title: One-tube smart genetic testing via coupling isothermal amplification and three-way nucleic acid circuit to glucometers

text: Abstract Urgent demand for portable diagnosis has promoted a new sensing strategy that uses personal glucometer (PGM) to detect non-glucose targets. Even though great progresses have been achieved in terms of target range and sensing principle, issues such as low final signal-to-background ratio and hard-to-realize one-tube smart analysis still exist and challenge real-world applications in gene detection. Here we propose a practical solution via coupling isothermal amplification (i.e. LAMP) and three-way amplifiable catalytic hairpin assembly (i.e. CHA) to a PGM. It allows direct transduction from genomic information to commercial portable devices with all of ultra-high sensitivity, specificity and enhanced signal-to-noise ratio. Compared with previous report without signal amplification, the introduction of CHA has successfully improved the signal amplitude by at least 12.5 folds. More importantly, through importing an effective three-way junction based transduction, we also innovatively develop a one-tube logical or multiplex analysis strategy in PGM based detection. Totally four situations of two foodborne bacteria genes, in Cronobacter sakazakii (ompA) and Escherichia coli (malB), could be directly readout using the final PGM signals, with the lowest detection amount down to less than 100 molecular copies (6.6 × 10−18 M). It is believed such a LAMP-CHA-PGM method has been already sensitive, specific, and of great potential for practically portable gene diagnostics.


title: A transcriptional regulatory atlas of coronavirus infection of human cells

text: Identifying transcriptional responses that are most consistently associated with experimental coronavirus (CoV) infection can help illuminate human cellular signaling pathways impacted by CoV infection. Here, we distilled over 3,000,000 data points from publically archived CoV infection transcriptomic datasets into consensus regulatory signatures, or consensomes, that rank genes based on their transcriptional responsiveness to infection of human cells by MERS, SARS-CoV-1 and SARS-CoV-2 subtypes. We computed overlap between genes with elevated rankings in the CoV consensomes against those from transcriptomic and ChIP-Seq consensomes for nearly 880 cellular signaling pathway nodes. Validating the CoV infection consensomes, we identified robust overlap between their highly ranked genes and high confidence targets of signaling pathway nodes with known roles in CoV infection. We then developed a series of use cases that illustrate the utility of the CoV consensomes for hypothesis generation around mechanistic aspects of the cellular response to CoV infection. We make the CoV infection datasets and their universe of underlying data points freely accessible through the Signaling Pathways Project web knowledgebase at https://www.signalingpathways.org/datasets/index.jsf.


title: Detection of Host Response to Viral Respiratory Infection by Measurement of Messenger RNA for MxA, TRIM21, and Viperin in Nasal Swabs

text: Respiratory viruses frequently cause symptomatic infections in children but are often detected also in healthy children. We investigated myxovirus resistance protein A (MxA), viperin, and tripartite-motif 21 (TRIM21) messenger RNA indexes in nasal swabs as potential biomarkers of viral respiratory infection in children. Respiratory viruses were detected by polymerase chain reaction in the same swabs. Nasal MxA and viperin indexes were increased in symptomatic virus-positive children. Nasal viperin index was found to be a robust marker of viral respiratory tract infection with a sensitivity of 80% and specificity of 94% in distinguishing children with symptomatic virus infections from asymptomatic virus-negative children.


title: The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells

text: The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their ‘fresh’ host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its ‘fresh’ host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.


Intrauterine vertical transmission of SARS‐CoV‐2: what we know so far


title: Autopsy in critical illness: is it obsolete?

text: The autopsy continues to have important implications for patient management in critical illness. It is not obsolete. Autopsy data help us to track shifts in disease prevalence over time and to heighten surveillance for serious diagnoses that are commonly missed. These data help us to identify important contributors to death that may be remediated through quality assurance and control programs. In discrete patient subsets, information from autopsies may reinforce the degree of certainty surrounding end-of-life decision-making.


title: Measuring weight with e‐scales in clinical and research settings during the COVID‐19 pandemic

text: With the COVID‐19 pandemic, clinicians and researchers have been suddenly confronted with the difficulty of treatment provision and continuation of clinical trials without face‐to‐face contact. This predicament has resulted in the rapid adoption of telehealth methodologies.(1) Clinicians and researchers focused on obesity management have an additional need‐‐ a remote way to measure weight. In this piece, we will describe electronic scales (e‐scales) and provide guidance on how clinicians/researchers might best implement e‐scales in their clinical practice or research studies to remotely measure weight.


title: Metformin and COVID‐19: A novel deal of an Old Drug

text: In 2002, China witnessed the emergence of a severe acute respiratory disease caused by coronavirus SARS‐CoV. Ten years later in 2012 a new version of the virus appeared in the Middle East known as Middle East Respiratory Syndrome Coronavirus MERS‐CoV. At the end of 2019, the Chinese Center for Disease Control and Prevention (China CDC) recorded a pneumonia of unknown causes. Epidemiologically, the pneumonia was linked to a wet animal and seafood wholesale market in Wuhan, Hubei Province, China, later Known by COVID‐19. The COVID‐19 is a global pandemic infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Till now the total number of confirmed cases is 2,709,483 in over 225 countries around the world. A recent report indicates that obesity may responsible for increasing the mortality of COVID‐19 in Italy rather than in China. Here we would like to shed light on a new suggestion to decrease the mortality rate of COVID‐19. This article is protected by copyright. All rights reserved.


Novel Hepatitis E Virus in Ferrets, the Netherlands


title: The Canarypox-virus vaccine vector ALVAC triggers the release of IFN-γ by Natural Killer (NK) cells enhancing Th1 polarization

text: We investigated the mechanism by which ALVAC activates innate immunity. Combining ALVAC with protein antigens significantly augmented antigen-specific IgG2a responses; this was dependent on the presence of bioactive interferon (IFN)-γ. Immuno-depletion of NK cells prior to ALVAC immunisation abrogated IFN-γ production indicating that they are the main cellular source of early IFN-γ in vivo. Murine bone-marrow derived dendritic cells (BMDCs) cultured in the presence of ALVAC secreted high levels of the chemokines CXCL10 and CCL2 and up-regulated expression of the maturation markers CD40, CD80 and CD86. Therefore, we conclude that ALVAC acts as an adjuvant through a mechanism requiring NK cell derived IFN-γ, DC activation and chemokine secretion.


title: Emerging lethal infectious bronchitis coronavirus variants with multiorgan tropism

text: Infectious bronchitis virus (IBV) causes respiratory diseases in chickens and poses an economic threat to the poultry industry worldwide. Despite vaccine use, there have been field outbreaks of IBV in Taiwan. This study aimed to characterize the emerging IBV variants circulating in Taiwan. The analysis of the structural protein genes showed that these variants emerged through frequent recombination events among Taiwan strains, China strains, Japan strains and vaccine strains. Cross‐neutralization tests revealed that two of the variants exhibited novel serotypes. Clinicopathological assessment showed that two of the variants caused high fatality rates of 67% and 20% in one‐day‐old SPF chicks, and all the variants possessed multiorgan tropisms, including trachea, proventriculus and urogenital tissues. Furthermore, the commercial live‐attenuated Mass‐type vaccine conferred poor protection against these variants. This study identified novel genotypes, serotypes and pathotypes of emerging IBV variants circulating in Taiwan. There is an urgent need for effective countermeasures against these variant strains.


title: Optimal control and bifurcation diagram for a model nonlinear fractional SIRC

text: Abstract In this article, the optimal control for nonlinear SIRC model is studied in fractional order using the Caputo fractional derivative. Graph signal flow is given of the model and simulated by Simulink/Matlab which helps in discussing the topological structure of the model. Dynamics of the system versus certain parameters are studied via bifurcation diagrams, Lyapunov exponents and Poincare maps. The existence of a uniformly stable solution is proved after control. The obtained results display the activeness and suitability of the Mittag Generalized-Leffler function method (MGLFM). The approximate solution of the fractional order SIRC model using MGLFM is explained by giving the figures of solutions before and after control. Also, we plot the 3D relationships with different alpha (fractional order) which display the originality and suitability of the results.