title: Tocilizumab in patients with severe COVID-19: a retrospective cohort study

text: BACKGROUND: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment. METHODS: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score. FINDINGS: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40–0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001). INTERPRETATION: Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia. FUNDING: None.


Definitive Airway Management of Patients with a King Laryngeal Tube(™) in Place in the COVID-19 Pandemic


The chain of communication in health science: from researcher to health worker through open access


title: MERS-CoV infection among healthcare workers and risk factors for death: Retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018

text: Abstract Background Approximately half of the reported laboratory-confirmed infections of Middle East respiratory syndrome coronavirus (MERS-CoV) have occurred in healthcare settings, and healthcare workers constitute over one third of all secondary infections. This study aimed to describe secondary cases of MERS-CoV infection among healthcare workers and to identify risk factors for death. Methods A retrospective analysis was conducted on epidemiological data of laboratory-confirmed MERS-CoV cases reported to the World Health Organization from September 2012 to 2 June 2018. We compared all secondary cases among healthcare workers with secondary cases among non-healthcare workers. Multivariable logistic regression identified risk factors for death. Results Of the 2223 laboratory-confirmed MERS-CoV cases reported to WHO, 415 were healthcare workers and 1783 were non-healthcare workers. Compared with non-healthcare workers cases, healthcare workers cases were younger (P < 0.001), more likely to be female (P < 0.001), non-nationals (P < 0.001) and asymptomatic (P < 0.001), and have fewer comorbidities (P < 0.001) and higher rates of survival (P < 0.001). Year of infection (2013–2018) and having no comorbidities were independent protective factors against death among secondary healthcare workers cases. Conclusion Being able to protect healthcare workers from high threat respiratory pathogens, such as MERS-CoV is important for being able to reduce secondary transmission of MERS-CoV in healthcare-associated outbreaks. By extension, reducing infection in healthcare workers improves continuity of care for all patients within healthcare facilities.


title: Asymmetric effects of investor sentiment on industry stock returns: Panel data evidence

text: Abstract This article employs a state-of-the-art panel threshold model by allowing for regime intercepts, in order to shed new light on the asymmetric/nonlinear effects of local and global sentiments on expected industry stock returns among 11 Asian countries during the period from 1996 to 2010. Empirical evidence demonstrates that once the regime intercept is included, the asymmetric effects of global sentiment on oil & gas, financials, and health care industry returns become less under optimism, as compared with under pessimism. More critically, the positive (negative) impact of global sentiment above (under) the threshold turns significant, indicating that global optimism leads industry returns to be overvalued, while pessimism leads them to be undervalued. For local market sentiment, our results support that higher local sentiment enhances the returns of basic materials, telecommunications, and utilities industries. The empirical results confirm that the nexus of industry returns and investor sentiments is subject to change between different sentimental intervals.


title: Post-exposure prophylaxis or pre-emptive therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): study protocol for a pragmatic randomized-controlled trial

text: BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 causing the coronavirus disease (COVID-19) pandemic. Currently, there is a lack of evidence-based therapies to prevent COVID-19 following exposure to the virus, or to prevent worsening of symptoms following confirmed infection. We describe the design of a clinical trial of hydroxychloroquine for post-exposure prophylaxis (PEP) and pre-emptive therapy (PET) for COVID-19. METHODS: We will conduct two nested multicentre international double-blind randomized placebo-controlled clinical trials of hydroxychloroquine for: 1) PEP of asymptomatic household contacts or healthcare workers exposed to COVID-19 within the past four days, and 2) PET for symptomatic outpatients with COVID-19 showing symptoms for less than four days. We will recruit 1,500 patients each for the PEP and PET trials. Participants will be randomized 1:1 to receive five days of hydroxychloroquine or placebo. The primary PEP trial outcome will be the incidence of symptomatic COVID-19. The primary PET trial outcome will be an ordinal scale of disease severity (not hospitalized, hospitalized without intensive care, hospitalization with intensive care, or death). Participant screening, informed consent, and follow-up will be exclusively internet-based with appropriate regulatory and research ethics board approvals in Canada and the United States. DISCUSSION: These complementary randomized-controlled trials are innovatively designed and adequately powered to rapidly answer urgent questions regarding the effectiveness of hydroxychloroquine to reduce virus transmission and disease severity of COVID-19 during a pandemic. In-person participant follow-up will not be conducted to facilitate social distancing strategies and reduce risks of exposure to study personnel. Innovative trial approaches are needed to urgently assess therapeutic options to mitigate the global impact of this pandemic. TRIALS REGISTRATION: clinicaltrials.gov (NCT04308668); registered 16 March, 2020.


title: Antagonism of dsRNA-Induced Innate Immune Pathways by NS4a and NS4b Accessory Proteins during MERS Coronavirus Infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified in 2012 as a novel etiological agent of severe respiratory disease in humans. As during infection by other viruses, host sensing of viral double-stranded RNA (dsRNA) induces several antiviral pathways. These include interferon (IFN), oligoadenylate synthetase (OAS)-RNase L, and protein kinase R (PKR). Coronaviruses, including MERS-CoV, potently suppress the activation of these pathways, inducing only modest host responses. Our study describes the functions of two accessory proteins unique to MERS-CoV and related viruses, NS4a and NS4b, during infection in human airway epithelium-derived A549 cells. NS4a has been previously characterized as a dsRNA binding protein, while NS4b is a 2′,5′-phosphodiesterase with structural and enzymatic similarity to NS2 encoded by mouse hepatitis virus (MHV). We found that deletion of NS4a results in increased interferon lambda (IFNL1) expression, as does mutation of either the catalytic site or nuclear localization sequence of NS4b. All of the mutant viruses we tested exhibited slight decreases in replication. We previously reported that, like MHV NS2, NS4b antagonizes OAS-RNase L, but suppression of IFN is a previously unidentified function for viral phosphodiesterases. Unexpectedly, deletion of NS4a does not result in robust activation of the PKR or OAS-RNase L pathways. Therefore, MERS-CoV likely encodes other proteins that contribute to suppression or evasion of these antiviral innate immune pathways that should be an important focus of future work. This study provides additional insight into the complex interactions between MERS-CoV and the host immune response.


title: Quantitative mapping of patented technology — The case of electrical conducting polymer nanocomposite

text: Abstract This study aims to obtain global technology evolution by constructing and analyzing patent citation network and patent citation map for the field of electrical conducting polymer nanocomposite. A total of 1421 patents are retrieved from USPTO patent database and patent citation network is established by combing both patent citation and social network analysis. Network properties, e.g. Degree Centrality, Betweenness Centrality, and Closeness Centrality, are calculated for representing several technology evolution mechanisms that first proposed in this study. Also, a distance-based patent citation map is constructed by calculating relative distances and positions of patents in the patent citation network. Quantitative ways of exploring technology evolution are investigated in this study to unveil important or emerging techniques as well as to demonstrate dynamics and visualization of technology evolutions.


title: Identifying potential emerging threats through epidemic intelligence activities—looking for the needle in the haystack?

text: Abstract Background Epidemic intelligence (EI) for emerging infections is the process of identifying key information on emerging infectious diseases and specific incidents. Automated web-based infectious disease surveillance technologies are available; however, human input is still needed to review, validate, and interpret these sources. In this study, entries captured by Public Health England’s (PHE) manual event-based EI system were examined to inform future intelligence gathering activities. Methods A descriptive analysis of unique events captured in a database between 2013 and 2017 was conducted. The top five diseases in terms of the number of entries were described in depth to determine the effectiveness of PHE’s EI surveillance system compared to other sources. Results Between 2013 and 2017, a total of 22 847 unique entries were added to the database. The top three initial and definitive information sources varied considerably by disease. Ebola entries dominated the database, making up 23.7% of the total, followed by Zika (11.8%), Middle East respiratory syndrome (6.7%), cholera (5.5%), and yellow fever and undiagnosed morbidity (both 3.3%). Initial reports of major outbreaks due to the top five disease agents were picked up through the manual system prior to being publicly reported by official sources. Conclusions PHE’s manual EI process quickly and accurately detected global public health threats at the earliest stages and allowed for monitoring of events as they evolved.


title: Variation in Ventilator Allocation Guidelines by US State During the Coronavirus Disease 2019 Pandemic: A Systematic Review

text: IMPORTANCE: During the coronavirus disease 2019 pandemic, there may be too few ventilators to meet medical demands. It is unknown how many US states have ventilator allocation guidelines and how these state guidelines compare with one another. OBJECTIVE: To evaluate the number of publicly available US state guidelines for ventilator allocation and the variation in state recommendations for how ventilator allocation decisions should occur and to assess whether unique criteria exist for pediatric patients. EVIDENCE REVIEW: This systematic review evaluated publicly available guidelines about ventilator allocation for all states in the US and in the District of Columbia using department of health websites for each state and internet searches. Documents with any discussion of a process to triage mechanical ventilatory support during a public health emergency were screened for inclusion. Articles were excluded if they did not include specific ventilator allocation recommendations, were in draft status, did not include their state department of health, or were not the most up-to-date guideline. All documents were individually assessed and reassessed by 2 independent reviewers from March 30 to April 2 and May 8 to 10, 2020. FINDINGS: As of May 10, 2020, 26 states had publicly available ventilator guidelines, and 14 states had pediatric guidelines. Use of the Sequential Organ Failure Assessment score in the initial rank of adult patients was recommended in 15 state guidelines (58%), and assessment of limited life expectancy from underlying conditions or comorbidities was included in 6 state guidelines (23%). Priority was recommended for specific groups in the initial evaluation of patients in 6 states (23%) (ie, Illinois, Maryland, Massachusetts, Michigan, Pennsylvania, and Utah). Many states recommended exclusion criteria in adult (11 of 26 states [42%]) and pediatric (10 of 14 states [71%]) ventilator allocation. Withdrawal of mechanical ventilation from a patient to give to another if a shortage occurs was discussed in 22 of 26 adult guidelines (85%) and 9 of 14 pediatric guidelines (64%). CONCLUSIONS AND RELEVANCE: These findings suggest that although allocation guidelines for mechanical ventilatory support are essential in a public health emergency, only 26 US states provided public guidance on how this allocation should occur. Guidelines among states, including adjacent states, varied significantly and could cause inequity in the allocation of mechanical ventilatory support during a public health emergency, such as the coronavirus disease 2019 pandemic.


title: A recombinant nucleocapsid protein-based indirect enzyme-linked immunosorbent assay to detect antibodies against porcine deltacoronavirus

text: Recently, porcine deltacoronavirus (PDCoV) has been proven to be associated with enteric disease in piglets. Diagnostic tools for serological surveys of PDCoV remain in the developmental stage when compared with those for other porcine coronaviruses. In our study, an indirect enzyme-linked immunosorbent assay (ELISA) (rPDCoV-N-ELISA) was developed to detect antibodies against PDCoV using a histidine-tagged recombinant nucleocapsid (N) protein as an antigen. The rPDCoV-N-ELISA did not cross-react with antisera against porcine epidemic diarrhea virus, swine transmissible gastroenteritis virus, porcine group A rotavirus, classical swine fever virus, porcine circovirus-2, porcine pseudorabies virus, and porcine reproductive and respiratory syndrome virus; the receiver operating characteristic (ROC) curve analysis revealed 100% sensitivity and 90.4% specificity of the rPDCoV-N-ELISA based on samples of known status (n=62). Analyses of field samples (n=319) using the rPDCoV-N-ELISA indicated that 11.59% of samples were positive for antibodies against PDCoV. These data demonstrated that the rPDCoV-N-ELISA can be used for epidemiological investigations of PDCoV and that PDCoV had a low serum prevalence in pig population in Heilongjiang province, northeast China.


title: Pathogen exposure in endangered island fox (Urocyon littoralis) populations: Implications for conservation management

text: Abstract Island fox (Urocyon littoralis) populations on four California Channel Islands have declined severely since 1994. Canine distemper (CDV) was suspected to be responsible for the decline of the Santa Catalina Island fox, so knowledge of infectious disease exposure in the remaining island fox populations was urgently needed. This study reviewed previous pathogen exposure in island foxes and investigated the current threat by conducting a serologic survey of foxes on all islands and sympatric feral cats on three islands from 2001 to 2003 for antibodies against canid pathogens. Before the decline, foxes had evidence of exposure to CDV, canine adenovirus (CAV), canine parvovirus (CPV), and Toxoplasma, with exposure to these five pathogens differing greatly by island. Exposure to canine coronavirus (CCV), canine herpesvirus (CHV), and Leptospira was rare. In 2001–2003, wild-born foxes had evidence of exposure to CDV (5.2–32.8%) on 5 of 6 islands, CPV (28–100%) and CAV (4.7–100%) on five islands, and Toxoplasma gondii (2.3–15.4%) on four islands. Exposure to CCV, CHV and Leptospira was less common. Sharing of infectious agents between sympatric foxes and feral cats appeared minimal, but CDV exposure was detected in two cats on Santa Catalina Island. Domestic dogs have historically been present on the islands, but it is not known if canine diseases can be maintained in fox populations without the continual presence of dogs. Targeted vaccination programs against the most virulent pathogens and continued intensive disease surveillance may help protect the critically small remaining fox populations from disease outbreaks that could threaten the success of ongoing conservation efforts.


title: The impact of the COVID-19 pandemic on cardiac surgery and transplant services in Ireland’s National Centre

text: BACKGROUND: Irish health services have been repurposed in response to the COVID-19 pandemic. Critical care services have been re-focused on the management of COVID-19 patients. This presents a major challenge for specialities such as cardiothoracic surgery that are reliant on intensive care unit (ICU) resources. AIM: The aim of this study was to evaluate the impact of the COVID-19 pandemic on activity at the cardiothoracic surgical care at the National Cardiothoracic Surgery and Transplant Centre. METHODS: A comparison was performed of cardiac surgery and transplant caseload for the first 4 months of 2019 and 2020 using data collected prospectively on a customised digital database. RESULTS: Cardiac surgery activity fell over the study period but was most impacted in March and April 2020. Operative activity fell to 49% of the previous years’ activity for March and April 2020. Surgical acuity changed with 61% of all cases performed as inpatient transfers after cardiology admission in contrast with a 40% rate in 2019. Valve surgery continued at 89% of the expected rate; coronary artery bypass surgery was performed at 61% of the expected rate and major aortic surgery at 22%. Adult congenital heart cases were not performed in March or April 2020. One heart and one lung transplant were performed in this period. CONCLUSIONS: In March and April of 2020, the spread of COVID-19 and the resultant focus on its management resulted in a reduction in cardiothoracic surgery service delivery.


Hypotension, Systemic Inflammatory Response Syndrome, and Coronavirus Disease 2019: A Clinical Conundrum


A fatal case caused by novel H7N9 avian influenza A virus in China


title: Arterivirus Nsp1 Modulates the Accumulation of Minus-Strand Templates to Control the Relative Abundance of Viral mRNAs

text: The gene expression of plus-strand RNA viruses with a polycistronic genome depends on translation and replication of the genomic mRNA, as well as synthesis of subgenomic (sg) mRNAs. Arteriviruses and coronaviruses, distantly related members of the nidovirus order, employ a unique mechanism of discontinuous minus-strand RNA synthesis to generate subgenome-length templates for the synthesis of a nested set of sg mRNAs. Non-structural protein 1 (nsp1) of the arterivirus equine arteritis virus (EAV), a multifunctional regulator of viral RNA synthesis and virion biogenesis, was previously implicated in controlling the balance between genome replication and sg mRNA synthesis. Here, we employed reverse and forward genetics to gain insight into the multiple regulatory roles of nsp1. Our analysis revealed that the relative abundance of viral mRNAs is tightly controlled by an intricate network of interactions involving all nsp1 subdomains. Distinct nsp1 mutations affected the quantitative balance among viral mRNA species, and our data implicate nsp1 in controlling the accumulation of full-length and subgenome-length minus-strand templates for viral mRNA synthesis. The moderate differential changes in viral mRNA abundance of nsp1 mutants resulted in similarly altered viral protein levels, but progeny virus yields were greatly reduced. Pseudorevertant analysis provided compelling genetic evidence that balanced EAV mRNA accumulation is critical for efficient virus production. This first report on protein-mediated, mRNA-specific control of nidovirus RNA synthesis reveals the existence of an integral control mechanism to fine-tune replication, sg mRNA synthesis, and virus production, and establishes a major role for nsp1 in coordinating the arterivirus replicative cycle.


title: COVID‐19 prompts new executive orders from Minnesota governor

text: Minnesota Governor Tim Walz has signed Executive Orders 20‐28 and 20‐29, which will expand mental health counseling options for Minnesotans and streamline the process for Minnesotans applying for unemployment insurance, Minnesota Bring Me the News reported April 6. Executive Order 20‐28 authorizes out‐of‐state mental health providers to treat Minnesota patients via telehealth services to “help ensure that the mental health needs of Minnesotans are met during the stress and uncertainty of the COVID‐19 pandemic.” The order notes that many Minnesotans receive mental health care from providers in neighboring states, and this order will allow them to continue that care via virtual means. Gov. Walz has been trying to expand Minnesota's mental health care options during COVID‐19, asking President Trump for a major disaster declaration so the state can be reimbursed for expanding community‐based crisis counseling services. Executive Order 20‐29 amends a previous order, EO 20‐05, that was designed to help Minnesotans get unemployment insurance as quickly as possible rather than waiting the previous week following the loss of their jobs. Gov. Walz also announced $6.2 million in financial assistance grants that is earmarked for Minnesota veterans and their families who have been impacted by COVID‐19 and will provide one‐time payments of $1,000.


title: Detection of enteroviruses using cDNA and synthetic oligonucleotide probes

text: Abstract This study compares the detection of enterovirus RNA by cDNA probes prepared from both the 5' and 3' end of the genome of coxsackíe A21 and B4 with the use of synthetic oligonucleotides prepared from short but highly conserved sequences in the 5' end non-coding region of the picornavirus genome. The cDNA probes detected enteroviruses with a variable level of sensitivity which presumably depended on the degree of genomic homology with the detecting probes. Generally probes from coxsackievirus A21 detected more enteroviruses than did similar probes from coxsackievirus B4. Probes from the 5' end of the genome of both viruses were more sensitive than 3' end probes. In contrast, synthetic oligonucleotides detected all enteroviruses efficiently suggesting that these probes could be useful as ‘universal’ probes to detect any enterovirus. This paper discusses the application of these probes in the diagnosis and differentiation of enteroviruses.


title: Packaging of Rift Valley fever virus pseudoviruses and establishment of a neutralization assay method

text: Rift Valley fever (RVF) is an acute, febrile zoonotic disease that is caused by the RVF virus (RVFV). RVF is mainly prevalent on the Arabian Peninsula, the African continent, and several islands in the Indian Ocean near southeast Africa. RVFV has been classified by the World Organisation for Animal Health (OIE) as a category A pathogen. To avoid biological safety concerns associated with use of the pathogen in RVFV neutralization assays, the present study investigated and established an RVFV pseudovirus-based neutralization assay. This study used the human immunodeficiency virus (HIV) lentiviral packaging system and RVFV structural proteins to successfully construct RVFV pseudoviruses. Electron microscopy observation and western blotting indicated that the size, structure, and shape of the packaged pseudoviruses were notably similar to those of HIV lentiviral vectors. Infection inhibition assay results showed that an antibody against RVFV inhibited the infective ability of the RVFV pseudoviruses, and an antibody neutralization assay for RVFV detection was then established. This study has successfully established a neutralization assay based on RVFV pseudoviruses and demonstrated that this method can be used to effectively evaluate antibody neutralization.


title: Les grands exclus face à la pandémie

text: Résumé Face à la pandémie de corona virus, les grands exclus de nos sociétés contemporaines expriment des besoins divers autres qu’alimentaires : besoins de repères, de parole, de reconnaissance de dignité et de soins. Il nous appartient de les prendre aussi en compte comme essentiels. Summary Faced with the corona virus pandemic, those leaving in total exclusion of our modern societies express various needs other than food: needs of reference points, communication, care and recognition of human dignity. It is our responsibility to consider these needs as essential.


Etiologies of Acute Respiratory Tract Infections


title: Antibody responses in spiral colon, ileum, and jejunum of bovine coronavirus-infected neonatal calves

text: Abstract A preliminary study was conducted to compare the regional intestinal immune responses of neonatal calves inoculated with virulent or attenuated bovine coronavirus (BCV) to determine the cause of reported vaccine failures. A group of 9 newborn, colostrum-deprived calves was used; two calves were inoculated with attenuated virus, four calves were infected with virulent virus (including one naturally infected calf), and three calves were uninfected controls. Calves inoculated with virulent virus produced higher titers of BCV antibodies in the intestines than those inoculated with the attenuated virus. The failure of the calves to respond to the attenuated virus was apparently due to the inability of the virus to replicate to high titers. Spiral colon, ileum, and jejunum were found to be immunologically distinct; the highest anti-BCV antibody responses were detected in spiral colon, the primary site of infection, and involved all four isotypes of bovine immunoglobulins. The antibody response in ileum was lower than in spiral colon. The immune responses developed slowly in jejunum and were associated primarily with the IgG subtypes.


title: Phylogenetic Tracings of Proteome Size Support the Gradual Accretion of Protein Structural Domains and the Early Origin of Viruses from Primordial Cells

text: Untangling the origin and evolution of viruses remains a challenging proposition. We recently studied the global distribution of protein domain structures in thousands of completely sequenced viral and cellular proteomes with comparative genomics, phylogenomics, and multidimensional scaling methods. A tree of life describing the evolution of proteomes revealed viruses emerging from the base of the tree as a fourth supergroup of life. A tree of domains indicated an early origin of modern viral lineages from ancient cells that co-existed with the cellular ancestors. However, it was recently argued that the rooting of our trees and the basal placement of viruses was artifactually induced by small genome (proteome) size. Here we show that these claims arise from misunderstanding and misinterpretations of cladistic methodology. Trees are reconstructed unrooted, and thus, their topologies cannot be distorted a posteriori by the rooting methodology. Tracing proteome size in trees and multidimensional views of evolutionary relationships as well as tests of leaf stability and exclusion/inclusion of taxa demonstrated that the smallest proteomes were neither attracted toward the root nor caused any topological distortions of the trees. Simulations confirmed that taxa clustering patterns were independent of proteome size and were determined by the presence of known evolutionary relatives in data matrices, highlighting the need for broader taxon sampling in phylogeny reconstruction. Instead, phylogenetic tracings of proteome size revealed a slowdown in innovation of the structural domain vocabulary and four regimes of allometric scaling that reflected a Heaps law. These regimes explained increasing economies of scale in the evolutionary growth and accretion of kernel proteome repertoires of viruses and cellular organisms that resemble growth of human languages with limited vocabulary sizes. Results reconcile dynamic and static views of domain frequency distributions that are consistent with the axiom of spatiotemporal continuity that is tenet of evolutionary thinking.


title: Detection and molecular chracterization of porcine type 3 orthoreoviruses circulating in South Korea

text: Abstract Orthoreoviruses infect virtually all mammalian species, causing systemic infections including mild gastrointestinal and respiratory illnesses. However, little is known about the prevalence or genetic diversity of porcine orthoreoviruses in South Korea. We examined 237 diarrheic fecal samples collected from 78 pig farms around the country. RT-PCR utilizing primers specific for the L1 gene of mammalian orthoreoviruses showed that 45 (19.0%) samples were positive. The 10 strains isolated from orthoreovirus-positive samples formed typical perinuclear cytoplasmic inclusion bodies and had an atypical hemagglutination pattern; these are characteristics of type 3 orthoreovirus. Phylogenetic analysis of the S1 gene in these 10 Korean and other strains showed that type 3 orthoreoviruses could be divided into four lineages; the 10 Korean strains were included in porcine lineage IV, along with T3/porcine/Sichuan/2006. Sequence analysis showed that strains in lineage IV had nucleotide identities of 97.0–98.1% and deduced amino acid identities of 96.4–98.2%. Sequence analysis of the σ1 protein, a viral attachment protein, revealed that the amino acid sequences associated with neurotropism (amino acids 198–204, 249I, 350D, and 419E) were highly conserved among the Korean strains, confirming that neural tropism was present. In conclusion, our findings suggest that porcine orthoreovirus infections are endemic in pig farms in South Korea and that the 10 novel Korean porcine orthoreoviruses belong to porcine lineage IV of type 3 orthoreovirus. In addition, sequence analysis of S1 genes encoding the σ1 protein showed that the 9 of 10 Korean porcine orthoreoviruses exhibited neural tropism.


title: Unravelling potential severe psychiatric repercussions on healthcare professionals during the COVID-19 crisis

text: The coronavirus disease 2019 (COVID-19) outbreak is putting healthcare professionals, especially those in the frontline, under extreme pressures, with a high risk of experiencing physical exhaustion, psychological disturbances, stigmatization, insomnia, depression and anxiety. We report the case of a general practitioner, without relevant somatic or psychiatric history that experienced a “brief reactive psychosis (298.8)” under stressful circumstances derived from COVID-19. She presented with delusional ideas of catastrophe regarding the current pandemic situation, delusions of self-reference, surveillance and persecution, with high affective and behavioural involvement. Physical examination and all further additional investigations did not reveal any secondary causes. She was administered olanzapine 10 mg with significant psychopathological improvement being later discharged with indications to maintain the treatment. To our knowledge this is the first reported case of severe mental illness in a healthcare professional without previous psychiatric history due to COVID-19 outbreak. Around 85% of patients presenting a brief psychotic disorder will develop a potentially disabling serious psychotic illness in the long-term. This case represents the potentially serious mental health consequences on healthcare professionals throughout the COVID-19 crisis and emphasizes the need to implement urgent measures to maintain staff mental health during the current pandemic.


title: COVID‐19 heath crisis: less colorectal resections and yet no more peritonitis or bowel obstruction as a collateral effect?

text: Because of the rapid worldwide propagation of COVID‐19 (coronavirus disease 2019), each health care system had to urgently adapt with all efforts aimed to maximize the capacity of treatment for infected patients. With this in mind, the President of the French Republic declared on March 12, 2020: “Non‐essential hospital care will be postponed, i.e. surgical procedures that are not urgent.” But, in spite of the effort deployed by each hospital to provide a sufficient capacity of treatment for patients requiring a surgical procedure as an emergency, we have observed that the management of these patients have been largely affected, not because of a lack of resources but because of a surprising lack of patients.


title: Discretionary Fiscal Responses to the Covid-19 Pandemic

text: We analyse discretionary fiscal responses to the Covid-19 pandemic. We distinguish policies for three phases of the pandemic: (1) acute overall disruption, (2) initial recovery phase and (3) the longer term. We analyse measures already taken in (1) and consider measures relevant for (2). We distinguish between lump-sum subsidies, such as deferral of tax payments, which may ease financial constraints, and measures which intentionally affect incentives. We also identify factors that are important given the short-term nature of the measures.


title: Detecting signals of chronic shedding to explain pathogen persistence: Leptospira interrogans in California sea lions

text: 1. Identifying mechanisms driving pathogen persistence is a vital component of wildlife disease ecology and control. Asymptomatic, chronically infected individuals are an oft‐cited potential reservoir of infection, but demonstrations of the importance of chronic shedding to pathogen persistence at the population‐level remain scarce. 2. Studying chronic shedding using commonly collected disease data is hampered by numerous challenges, including short‐term surveillance that focuses on single epidemics and acutely ill individuals, the subtle dynamical influence of chronic shedding relative to more obvious epidemic drivers, and poor ability to differentiate between the effects of population prevalence of chronic shedding vs. intensity and duration of chronic shedding in individuals. 3. We use chronic shedding of Leptospira interrogans serovar Pomona in California sea lions (Zalophus californianus) as a case study to illustrate how these challenges can be addressed. Using leptospirosis‐induced strands as a measure of disease incidence, we fit models with and without chronic shedding, and with different seasonal drivers, to determine the time‐scale over which chronic shedding is detectable and the interactions between chronic shedding and seasonal drivers needed to explain persistence and outbreak patterns. 4. Chronic shedding can enable persistence of L. interrogans within the sea lion population. However, the importance of chronic shedding was only apparent when surveillance data included at least two outbreaks and the intervening inter‐epidemic trough during which fadeout of transmission was most likely. Seasonal transmission, as opposed to seasonal recruitment of susceptibles, was the dominant driver of seasonality in this system, and both seasonal factors had limited impact on long‐term pathogen persistence. 5. We show that the temporal extent of surveillance data can have a dramatic impact on inferences about population processes, where the failure to identify both short‐ and long‐term ecological drivers can have cascading impacts on understanding higher order ecological phenomena, such as pathogen persistence.


COVID-19–associated Pulmonary Aspergillosis


Closed Total Laryngectomy During The Covid‐19 Pandemic Disease


title: Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

text: The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.


title: Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico

text: The internal ribosomal entry site (IRES) functions as cap-independent translation initiation sites in eukaryotic cells. IRES elements have been applied as useful tools for bi-cistronic expression vectors. Current RNA structure prediction programs are unable to predict precisely the potential IRES element. We have designed a viral IRES prediction system (VIPS) to perform the IRES secondary structure prediction. In order to obtain better results for the IRES prediction, the VIPS can evaluate and predict for all four different groups of IRESs with a higher accuracy. RNA secondary structure prediction, comparison, and pseudoknot prediction programs were implemented to form the three-stage procedure for the VIPS. The backbone of VIPS includes: the RNAL fold program, aimed to predict local RNA secondary structures by minimum free energy method; the RNA Align program, intended to compare predicted structures; and pknotsRG program, used to calculate the pseudoknot structure. VIPS was evaluated by using UTR database, IRES database and Virus database, and the accuracy rate of VIPS was assessed as 98.53%, 90.80%, 82.36% and 80.41% for IRES groups 1, 2, 3, and 4, respectively. This advance useful search approach for IRES structures will facilitate IRES related studies. The VIPS on-line website service is available at http://140.135.61.250/vips/.


title: Viral triggers of multiple sclerosis

text: Abstract Genetic and environmental factors jointly determine the susceptibility to develop Multiple Sclerosis (MS). Collaborative efforts during the past years achieved substantial progress in defining the genetic architecture, underlying susceptibility to MS. Similar to other autoimmune diseases, HLA-DR and HLA-DQ alleles within the HLA class II region on chromosome 6p21 are the highest-risk-conferring genes. Less-robust susceptibility effects have been identified for MHC class I alleles and for non-MHC regions. The role of environmental risk factors and their interaction with genetic susceptibility alleles are much less well defined, despite the fact that infections have long been associated with MS development. Current data suggest that infectious triggers are most likely ubiquitous, i.e., highly prevalent in the general population, and that they require a permissive genetic trait which predisposes for MS development. In this review article, we illustrate mechanisms of infection-induced immunopathologies in experimental animal models of autoimmune CNS inflammation, discuss challenges for the translation of these experimental data into human immunology research, and provide future perspectives on how novel model systems could be utilized to better define the role of viral pathogens in MS.


title: Evaluation of the potential incidence of COVID-19 and effectiveness of containment measures in Spain: a data-driven approach

text: BACKGROUND: We are currently experiencing an unprecedented challenge, managing and containing an outbreak of a new coronavirus disease known as COVID-19. While China—where the outbreak started—seems to have been able to contain the growth of the epidemic, different outbreaks are nowadays present in multiple countries. Nonetheless, authorities have taken action and implemented containment measures, even if not everything is known. METHODS: To facilitate this task, we have studied the effect of different containment strategies that can be put into effect. Our work referred initially to the situation in Spain as of February 28, 2020, where a few dozens of cases had been detected, but has been updated to match the current situation as of 13 April. We implemented an SEIR metapopulation model that allows tracing explicitly the spatial spread of the disease through data-driven stochastic simulations. RESULTS: Our results are in line with the most recent recommendations from the World Health Organization, namely, that the best strategy is the early detection and isolation of individuals with symptoms, followed by interventions and public recommendations aimed at reducing the transmissibility of the disease, which, although might not be sufficient for disease eradication, would produce as a second order effect a delay of several days in the raise of the number of infected cases. CONCLUSIONS: Many quantitative aspects of the natural history of the disease are still unknown, such as the amount of possible asymptomatic spreading or the role of age in both the susceptibility and mortality of the disease. However, preparedness plans and mitigation interventions should be ready for quick and efficacious deployment globally. The scenarios evaluated here through data-driven simulations indicate that measures aimed at reducing individuals’ flow are much less effective than others intended for early case identification and isolation. Therefore, resources should be directed towards detecting as many and as fast as possible the new cases and isolate them.


title: Insect Contribution to Horizontal Transmission of Reticuloendotheliosis virus

text: The involvement of insects in Reticuloendotheliosis virus (REV) transmission was examined by testing insects trapped at commercial farms and by controlled feeding experiments using mosquitoes, Culex pipiens L. and house flies, Musca domestica L. We established sensitive methods of REV detection, including reverse transcription-polymerase chain reaction (PCR) for REV-LTR and REV-gag genes, REV antigenemia measurements by enzyme-linked immunosorbent assay, and virus isolation in tissue cultures. A variety of blood-sucking species of insects were trapped at farms with infected poultry and tested, but none were positive. To rule out the possibility of PCR inhibition by insect RNA, spiking experiments were conducted and no interference was observed. Because Cx. pipiens mosquitoes were trapped frequently at farms, we performed feeding experiments with mosquito females fed on a REV-containing tissue culture medium and chicken blood mixture. Virus was detected in the mosquitoes up to 5 h postfeeding, compared with 96 h in the feeding mixture, indicating that Cx. pipiens can only harbor REV for a short period. House flies were suspected to be involved in the virus transmission because they frequently were trapped on positive farms. In contrast to mosquitoes, REV was harbored within the house fly digestive tract for up to 72 h and could infect chickens, as demonstrated by seroconversion and by detection of viral gag-sequence in the cloaca. The current study is supportive for the role of house flies as a mechanical vector of REV among poultry.


Epicardial Echocardiography – A Plausible Alternative Cardiac Imaging Technique in COVID-19 Pandemic


title: Autophagy: New Questions from Recent Answers

text: Macroautophagy (hereafter autophagy) is currently one of the areas of medical life sciences attracting a great interest because of its pathological implications and therapy potentials. The discovery of the autophagy-related genes (ATGs) has been the key event in this research field because their study has led to the acquisition of new knowledge about the mechanism of this transport pathway. In addition, the investigation of these genes in numerous model systems has revealed the central role that autophagy plays in maintaining the cell homeostasis. This process carries out numerous physiological functions, some of which were unpredicted and thus surprising. Here, we will review some of the questions about the mechanism and function of autophagy that still remain unanswered, and new ones that have emerged from the recent discoveries.


title: Animal viral diseases and global change: bluetongue and West Nile fever as paradigms

text: Environmental changes have an undoubted influence on the appearance, distribution, and evolution of infectious diseases, and notably on those transmitted by vectors. Global change refers to environmental changes arising from human activities affecting the fundamental mechanisms operating in the biosphere. This paper discusses the changes observed in recent times with regard to some important arboviral (arthropod-borne viral) diseases of animals, and the role global change could have played in these variations. Two of the most important arboviral diseases of animals, bluetongue (BT) and West Nile fever/encephalitis (WNF), have been selected as models. In both cases, in the last 15 years an important leap forward has been observed, which has lead to considering them emerging diseases in different parts of the world. BT, affecting domestic ruminants, has recently afflicted livestock in Europe in an unprecedented epizootic, causing enormous economic losses. WNF affects wildlife (birds), domestic animals (equines), and humans, thus, beyond the economic consequences of its occurrence, as a zoonotic disease, it poses an important public health threat. West Nile virus (WNV) has expanded in the last 12 years worldwide, and particularly in the Americas, where it first occurred in 1999, extending throughout the Americas relentlessly since then, causing a severe epidemic of disastrous consequences for public health, wildlife, and livestock. In Europe, WNV is known long time ago, but it is since the last years of the twentieth century that its incidence has risen substantially. Circumstances such as global warming, changes in land use and water management, increase in travel, trade of animals, and others, can have an important influence in the observed changes in both diseases. The following question is raised: What is the contribution of global changes to the current increase of these diseases in the world?


title: Expression of SARS-coronavirus spike glycoprotein in Pichia pastoris

text: To establish a rapid and economical method for the expression of viral proteins in high yield and purity by Pichia pastoris, the S protein of the SARS-CoV was selected in this study. Six S glycoprotein fragments were expressed in Escherichia coli BL21 and yeast KM71H strains. After purification by affinity chromatography, the protein identities were confirmed by western blot analysis, N-terminal sequencing and mass spectrometry. The proteins expressed in E. coli were low in solubility and bound by GroEL. They still formed soluble aggregates even when the GroEL was removed by urea. The proteins expressed in P. pastoris were relatively soluble. The maximal yield of the RBD reached 46 mg/l with purity greater than 95%. Pull-down assay revealed that ACE2 was specifically captured from cell lysate, indicating that the RBD was biologically active. The glycosylated and deglycosylated RBD was then subjected to SEC and results showed that deglycosylated RBD formed soluble aggregates again. Taken together, pure and biological active RBD of the S protein could be expressed in P. pastoris, and the P. pastoris expression platform will be a good alternative for the expression of viral proteins, in particular, the highly glycosylated surface proteins that mediate the tissue tropism and viral entry.


title: Modeling the lockdown relaxation protocols of the Philippine government in response to the COVID-19 pandemic: An intuitionistic fuzzy DEMATEL analysis

text: The COVID-19 pandemic, which started at Wuhan, has shut down world economies, prompting governments to impose drastic lockdown measures of the economy and the society. As these measures are exhausted, non-COVID-19 related issues such as those associated with the mental and physical well-being of people under lockdowns became an emerging concern. As these issues are evident, not to mention the economic downturn, governments are currently looking at designing lockdown relaxation efforts by simultaneously considering both public health and economic restart. Without documented experiences to rely on, governments are resorting to trial-and-error approach in creating a lockdown exit strategy while preventing succeeding waves of cases that may overwhelm healthcare facilities. Thus, this work pioneers the use of the decision-making trial and evaluation laboratory (DEMATEL) method with intuitionistic fuzzy (IF) sets along with the domain of public health and the emerging COVID-19 pandemic. The DEMATEL handles the intertwined causal relationships among guideline protocols for the relaxation strategy. The intuitionistic fuzzy set theory addresses the vagueness and uncertainty of human judgments in the context of the DEMATEL. A case study of the Philippine government response for the lockdown exit is presented to evaluate the applicability of the proposed method. Findings reveal that compliance of minimum public health standards, limited movement of persons, suspension of physical classes, the prohibition of mass gatherings, non-operation of category IV industries, and non-operation of hotels or similar establishments are the most crucial protocols for such strategy. These findings offer practical insights for the government to allocate resources and impose measures to ensure their implementation, as well as for developing mitigation efforts to cushion their socio-economic impacts. Policy insights and avenues for future works are also discussed.


title: Direct costs of acute respiratory infections in a pediatric long‐term care facility

text: Acute respiratory tract infections (ARI) are a major burden in pediatric long‐term care. We analyzed the financial impact of ARI in 2012–2013. Costs associated with ARI during the respiratory viral season were ten times greater than during the non‐respiratory viral season, $31 224 and $3242 per 1000 patient‐days, respectively (P < 0·001). ARI are burdensome for pediatric long‐term care facilities not only because of the associated morbidity and mortality, but also due to the great financial costs of prevention.


title: Emerging and changing viral diseases in the new millennium

text: Most viral infections encountered in resource‐rich countries are relatively trivial and transient with perhaps fever, malaise, myalgia, rash (exanthema) and sometimes mucosal manifestations (enanthema), including oral in some. However, the apparent benignity may be illusory as some viral infections have unexpected consequences – such as the oncogenicity of some herpesviruses and human papillomaviruses. Infections are transmitted from various human or animal vectors, especially by close proximity, and the increasing movements of peoples across the globe, mean that infections hitherto confined largely to the tropics now appear worldwide. Global warming also increases the range of movement of vectors such as mosquitoes. Thus recent decades have seen a most dramatic change with the emergence globally also of new viral infections – notably human immunodeficiency viruses (HIV) – and the appearance of some other dangerous and sometimes lethal infections formerly seen mainly in, and reported from, resource‐poor areas especially in parts of Asia, Latin America and Africa. This study offers a brief update of the most salient new aspects of the important viral infections, especially those with known orofacial manifestations or other implications for oral health care.


title: Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study

text: BACKGROUND: We aimed to report the clinical characteristics of imported coronavirus disease-19 (COVID-19) in Jiangsu Province. METHODS: We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with WHO interim guidance in three Grade ⅢA hospitals of Jiangsu from Jan 22 to Feb 14, 2020. Real time RT-PCR was used to detect the new coronavirus in respiratory samples. RESULTS: Of the 80 patients infected with COVID-19, 41 patients were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. 9 patients were unconfirmed until a third-time nucleic acid test. 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 cases (78.75%) and 51 cases (-63.75%) respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (-68.75%) showed abnormal, 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Up to now, 21 cases were discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days. CONCLUSIONS: Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptivity. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that of Wuhan. Notably, infected patients may be falsely excluded based on two consecutively negative respiratory pathogenic nucleic acid test results.


title: The Adaptive Behavioral Components (ABC) Model for Planning Longitudinal Behavioral Technology-Based Health Interventions: A Theoretical Framework

text: A growing number of interventions incorporate digital and social technologies (eg, social media, mobile phone apps, and wearable devices) into their design for behavior change. However, because of a number of factors, including changing trends in the use of technology over time, results on the efficacy of these interventions have been mixed. An updated framework is needed to help researchers better plan behavioral technology interventions by anticipating the needed resources and potential changes in trends that may affect interventions over time. Focusing on the domain of health interventions as a use case, we present the Adaptive Behavioral Components (ABC) model for technology-based behavioral interventions. ABC is composed of five components: basic behavior change; intervention, or problem-focused characteristics; population, social, and behavioral characteristics; individual-level and personality characteristics; and technology characteristics. ABC was designed with the goals of (1) guiding high-level development for digital technology–based interventions; (2) helping interventionists consider, plan for, and adapt to potential barriers that may arise during longitudinal interventions; and (3) providing a framework to potentially help increase the consistency of findings among digital technology intervention studies. We describe the planning of an HIV prevention intervention as a case study for how to implement ABC into intervention design. Using the ABC model to plan future interventions might help to improve the design of and adherence to longitudinal behavior change intervention protocols; allow these interventions to adapt, anticipate, and prepare for changes that may arise over time; and help to potentially improve intervention behavior change outcomes. Additional research is needed on the influence of each of ABC’s components to help improve intervention design and implementation.


Guidance for resuming GI endoscopy and practice operations after the COVID-19 pandemic


title: Elucidation of the avian nucleolar proteome by quantitative proteomics using SILAC and changes in cells infected with the coronavirus infectious bronchitis virus

text: The nucleolus is a dynamic subnuclear compartment involved in ribosome subunit biogenesis, regulation of cell stress and modulation of cellular growth and the cell cycle, among other functions. The nucleolus is composed of complex protein/protein and protein/RNA interactions. It is a target of virus infection with many viral proteins being shown to localize to the nucleolus during infection. Perturbations to the structure of the nucleolus and its proteome have been predicted to play a role in both cellular and infectious disease. Stable isotope labeling with amino acids in cell culture coupled to LC‐MS/MS with bioinformatic analysis using Ingenuity Pathway Analysis was used to investigate whether the nucleolar proteome altered in virus‐infected cells. In this study, the avian nucleolar proteome was defined in the absence and presence of virus, in this case the positive strand RNA virus, avian coronavirus infectious bronchitis virus. Data sets, potential protein changes and the functional consequences of virus infection were validated using independent assays. These demonstrated that specific rather than generic changes occurred in the nucleolar proteome in infectious bronchitis virus‐infected cells.


title: IFITM1 is a tight junction protein that inhibits hepatitis C virus entry

text: Type 1 interferon (IFN) continues to be the foundation for the current standard of care combination therapy for chronic hepatitis C virus (HCV) infection, yet the component interferon-stimulated genes (ISGs) that mediate the antiviral actions of IFN are not fully defined. Interferon-induced transmembrane protein 1 (IFITM1) is an ISG product that suppresses early stage infection by a number of viruses through an as yet unknown mechanism of action. Moreover, the actions of IFITM1 on HCV infection are not fully elucidated. Here we identify IFITM1 as a hepatocyte tight junction protein and a potent anti-HCV effector molecule. IFITM1 expression is induced early during IFN treatment of hepatocytes and accumulates at hepatic tight junctions in HCV-infected human patient liver during IFN therapy. Additionally, we found that IFITM1 interacts with HCV co-receptors including CD81 and occludin to disrupt the process of viral entry. Thus, IFITM1 is an anti-HCV ISG whose actions impart control of HCV infection through interruption of viral coreceptor function. CONCLUSION: This study defines IFITM1 as an ISG effector with action against HCV entry. Design of therapy regimens to enhance IFITM1 expression should improve the virologic response among HCV patients undergoing treatment with type I IFN.


title: Experimental evidence of a pathogen invasion threshold

text: Host density thresholds to pathogen invasion separate regions of parameter space corresponding to endemic and disease-free states. The host density threshold is a central concept in theoretical epidemiology and a common target of human and wildlife disease control programmes, but there is mixed evidence supporting the existence of thresholds, especially in wildlife populations or for pathogens with complex transmission modes (e.g. environmental transmission). Here, we demonstrate the existence of a host density threshold for an environmentally transmitted pathogen by combining an epidemiological model with a microcosm experiment. Experimental epidemics consisted of replicate populations of naive crustacean zooplankton (Daphnia dentifera) hosts across a range of host densities (20–640 hosts l(−1)) that were exposed to an environmentally transmitted fungal pathogen (Metschnikowia bicuspidata). Epidemiological model simulations, parametrized independently of the experiment, qualitatively predicted experimental pathogen invasion thresholds. Variability in parameter estimates did not strongly influence outcomes, though systematic changes to key parameters have the potential to shift pathogen invasion thresholds. In summary, we provide one of the first clear experimental demonstrations of pathogen invasion thresholds in a replicated experimental system, and provide evidence that such thresholds may be predictable using independently constructed epidemiological models.


title: A three-step diagnosis of pediatric pneumonia at the emergency department using clinical predictors, C-reactive protein, and pneumococcal PCR

text: Recommendations for the management of community-acquired pneumonia (CAP) advocate that, in the absence of the clinical and laboratory findings typical of bacterial CAP, antibiotics are not required. However, the true value of the clinical and laboratory predictors of pediatric CAP still needs to be assessed. This prospective cohort study in three emergency departments enrolled 142 children with radiological pneumonia. Pneumonia with lung consolidation was the primary endpoint; complicated pneumonia (bacteremia, empyema, or pleural effusion) was the secondary endpoint. We showed that three clinical signs (unilateral hypoventilation, grunting, and absence of wheezing), elevated procalcitonin (PCT), C-reactive protein (CRP), negative nasopharyngeal viral PCR, or positive blood pneumococcal PCR (P-PCR) were significantly associated with both pneumonia with consolidation and complicated pneumonia. Children with negative clinical signs and low CRP values had a low probability of having pneumonia with consolidation (13%) or complicated pneumonia (6%). Associating the three clinical signs, CRP >80 mg/L and a positive P-PCR ruled in the diagnosis of complicated pneumonia with a positive predictive value of 75%. Conclusion: A model incorporating clinical signs and laboratory markers can effectively assess the risk of having pneumonia. Children with negative clinical signs and low CRP are at a low risk of having pneumonia. For children with positive clinical signs and high CRP, a positive blood pneumococcal PCR can more accurately confirm the diagnosis of pneumonia.


title: Povidone‐iodine gargle as a prophylactic intervention to interrupt the transmission of SARS‐CoV‐2

text: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-COV-2 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in January 2020. Human-to-Human transmission occurs through close contact with an infected person or surfaces that are contaminated with droplets or secretions.


title: Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure

text: This cohort study investigates whether the prone position is associated with improved oxygenation and decreased risk for intubation in spontaneously breathing patients with severe COVID-19 hypoxemic respiratory failure.


title: Diffusion‐weighted MR study of femoral head avascular necrosis in severe acute respiratory syndrome patients

text: PURPOSE: To evaluate the apparent diffusion coefficient (ADC) of femoral head avascular necrosis (AVN) in severe acute respiratory syndrome (SARS). MATERIALS AND METHODS: Seventy‐nine SARS patients with hip pain underwent both conventional and diffusion‐weighted MRI (b‐value = 0–1000 seconds/mm(2)). The abnormal regions on the diffusion‐weighted images were outlined by using the conventional images as guides, and the ADCs were calculated. The ADC differences between normal and AVN femoral heads were compared. RESULTS: Of the 158 hips examined, 28 had AVN (11 with bilateral hip AVN, three with right hip AVN, and three with left hip AVN). The mean ADC was markedly greater in the AVN femoral head (1.66 × 10(–3) mm(2)/second ± 0.20) than in the normal femoral head (0.47 × 10(–3) mm(2)/second ± 0.082; P < 0.0001). There was no overlap between the normal and AVN femoral heads. CONCLUSION: DWI can provide valuable information regarding the diffusion properties of femoral head AVN, and markedly increased diffusion was identified in AVN. J. Magn. Reson. Imaging 2005. © 2005 Wiley‐Liss, Inc.


title: Rhesus macaque IFITM3 gene polymorphisms and SIV infection

text: Interferon-induced transmembrane proteins (IFITMs) have been recognized as important antiviral effectors of the innate immune system, both in cell culture and in infected humans. In particular, polymorphisms of the human IFITM3 gene have been shown to affect disease severity and progression in influenza A virus (FLUAV) and human immunodeficiency virus (HIV) infection, respectively. Rhesus macaques (Macaca mulatta) are commonly used to model human infections and the experimental inoculation of these animals with simian immunodeficiency virus (SIV) is one of the best models for HIV/AIDS in humans. However, information on the role of IFITM3 in SIV infection of rhesus macaques is currently lacking. We show that rhesus macaque (rh) IFITM3 inhibits SIV and FLUAV entry in cell culture, although with moderately reduced efficiency as compared to its human counterpart. We further report the identification of 16 polymorphisms in the rhIFITM3 gene, three of which were exonic and synonymous while the remainder was located in non-coding regions. Employing previously characterized samples from two cohorts of SIV-infected rhesus macaques, we investigated the relationship between these rhIFITM3 polymorphisms and both AIDS-free survival time and virus load. In cohort 1, several intronic polymorphisms were significantly associated with virus load or survival. However, an association with both parameters was not observed and significance was lost in most cases when animals were stratified for the presence of MHC allele Mamu-A1*001. Moreover, no significant genotype-phenotype associations were detected in cohort 2. These results suggest that, although IFITM3 can inhibit SIV infection in cell culture, genetic variation in rhIFITM3 might have only a minor impact on the course of SIV infection in experimentally infected animals.


title: Rapid Titration of Measles and Other Viruses: Optimization with Determination of Replication Cycle Length

text: BACKGROUND: Measles virus (MV) is a member of the Paramyxoviridae family and an important human pathogen causing strong immunosuppression in affected individuals and a considerable number of deaths worldwide. Currently, measles is a re-emerging disease in developed countries. MV is usually quantified in infectious units as determined by limiting dilution and counting of plaque forming unit either directly (PFU method) or indirectly from random distribution in microwells (TCID50 method). Both methods are time-consuming (up to several days), cumbersome and, in the case of the PFU assay, possibly operator dependent. METHODS/FINDINGS: A rapid, optimized, accurate, and reliable technique for titration of measles virus was developed based on the detection of virus infected cells by flow cytometry, single round of infection and titer calculation according to the Poisson's law. The kinetics follow up of the number of infected cells after infection with serial dilutions of a virus allowed estimation of the duration of the replication cycle, and consequently, the optimal infection time. The assay was set up to quantify measles virus, vesicular stomatitis virus (VSV), and human immunodeficiency virus type 1 (HIV-1) using antibody labeling of viral glycoprotein, virus encoded fluorescent reporter protein and an inducible fluorescent-reporter cell line, respectively. CONCLUSION: Overall, performing the assay takes only 24–30 hours for MV strains, 12 hours for VSV, and 52 hours for HIV-1. The step-by-step procedure we have set up can be, in principle, applicable to accurately quantify any virus including lentiviral vectors, provided that a virus encoded gene product can be detected by flow cytometry.


title: Genomic variance of the 2019‐nCoV coronavirus

text: There is a rising global concern for the recently emerged novel coronavirus (2019‐nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019‐nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019‐nCoV. Despite the low heterogeneity of the 2019‐nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8‐encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti‐coronavirus approaches.


title: Barrier function of airway tract epithelium

text: Airway epithelium contributes significantly to the barrier function of airway tract. Mucociliary escalator, intercellular apical junctional complexes which regulate paracellular permeability and antimicrobial peptides secreted by the airway epithelial cells are the three primary components of barrier function of airway tract. These three components act cooperatively to clear inhaled pathogens, allergens and particulate matter without inducing inflammation and maintain tissue homeostasis. Therefore impairment of one or more of these essential components of barrier function may increase susceptibility to infection and promote exaggerated and prolonged innate immune responses to environmental factors including allergens and pathogens resulting in chronic inflammation. Here we review the regulation of components of barrier function with respect to chronic airways diseases.


title: A tracing method of airborne bacteria transmission across built environments

text: Abstract Disease transmission across built environments has been found to be a serious health risk. Airborne transmission is a vital route of disease infection caused by bacteria and virus. However, tracing methods of airborne bacteria in both lab and field research failed to veritably express the transporting process of microorganism in the air. A new tracing method of airborne bacteria used for airborne transmission was put forward and demonstrated its feasibility by conducting a field evaluation on the basis of genetic modification and bioaerosol technology. A specific gene fragment (pFPV-mCherry fluorescent protein plasmid) was introduced into nonpathogenic E. coli DH5α as tracer bacteria by high-voltage electroporation. Gel electrophoresis and DNA sequencing proved the success of the synthesis. Genetic stability, effect of aerosolization on the survival rate of tracer bacteria, and the application of the tracer bacteria to the airborne bacteria transmission were examined in both lab and field. Both the introduced plasmid stability rates of tracer E. coli in pre-aerosolization and post-aerosolization were above 95% in five test days. Survival rate of tracer E. coli at 97.5% ± 1.2% through aerosolization was obtained by an air-atomizer operated at an air pressure of 30 Psi. In the field experiment, the airborne transmission of E. coli between poultry houses was proved and emitted E. coli was more easily transmitted into self-house than adjacent house due to the ventilation design and weather condition. Our results suggested that the tracing method of airborne bacteria was available for the investigation of airborne microbial transmission across built environments.


title: Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing

text: COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14(++) monocytes with high inflammatory gene expression as well as a greater abundance of CD14(++)IL1β(+) monocytes in the ERS. CD4(+) T cells and CD8(+) T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.


title: Global sourcing strategy and sustainable competitive advantage

text: Abstract Global sourcing strategy has been one of the most hotly debated management trends in the last 20 years. In its early years, global sourcing was examined mostly from “in-house” development and procurement perspectives; and in the last several years, research focus has shifted to “outsourcing” activities. Along with this shift from internal to external focus on global sourcing, many researchers and business practitioners have applied a core competency argument to justify increased levels of outsourcing activities on a global basis. Although the beneficial aspects of outsourcing are assumed in most cases, no consensus exists in reality as to the effect of outsourcing. Furthermore, the increased instability of the exchange rate environment in the last several years has also led to increased difficulties in managing globally scattered operations that were once fashionable in the 1980s-90s under the rubric of global strategy. In this article, the authors explore potential limitations and negative consequences of outsourcing strategy on a global scale.


title: Factors Influencing the Response to Infectious Diseases: Focusing on the Case of SARS and MERS in South Korea

text: Following the 2003 the severe acute respiratory syndrome (SARS) and the 2015 Middle East Respiratory Syndrome (MERS) outbreak in South Korea, this research aims to explore and examine the factors influencing the response to infectious diseases, which encompasses both communicable and non-communicable diseases. Through a qualitative research method, this research categorizes the factors as inputs, processes and outputs and applies them into the 2003 SARS and MERS outbreak in South Korea. As the results conducted meta-analyses to comprehensively analyze the correlations of factors influencing disaster response from a Korean context, the findings show that the legislative factor had direct and indirect influence on the overall process of infectious disease response and that Leadership of the central government, establishment of an intergovernmental response system, the need for communication, information sharing and disclosure and onsite response were identified as key factors influencing effective infectious disease response.


title: Human metapneumovirus‐associated hospital admissions over five consecutive epidemic seasons: Evidence for alternating circulation of different genotypes

text: Human metapneumovirus (hMPV) is a pathogen of the respiratory tract with a worldwide distribution. The purpose of this study was to identify hMPV as the cause of acute respiratory diseases in children admitted at Spedali Civili, a public hospital in Brescia, Italy. Eight hundred forty‐six nasopharyngeal aspirate samples negative for the presence of other common respiratory viruses were tested for the presence of hMPV RNA by reverse transcription‐polymerase chain reaction. Of the 846 samples, 79 (9.3%) were positive for hMPV. Polymerase chain reaction products, obtained by amplification of the partial nucleotide sequence of gene F, were sequenced and compared with sequences deposited in GenBank. All four hMPV subtypes were identified, including the proposed subtype A2 sublineages “A” and “B”. In successive epidemic seasons, large outbreaks of hMPV alternated with small outbreaks in a biannual pattern. This local study provides further evidence that hMPV infection should be considered as a reason for hospital admission for acute respiratory disease in children. J. Med. Virol. 84:511–516, 2012. © 2011 Wiley Periodicals, Inc.


title: Analysis of the Transmissibility Change of 2019-Novel Coronavirus Pneumonia and Its Potential Factors in China from 2019 to 2020

text: BACKGROUND: Recently, a large-scale novel coronavirus pneumonia (NCP) outbreak swept China. As of Feb. 9, 2020, a total of 40,260 patients have been diagnosed with NCP, and 23,589 patients were suspected to have infected by the 2019 novel coronavirus (COVID-19), which puts forward a great challenge for public health and clinical treatment in China. Until now, we are in the high-incidence season of NCP. Thus, the analysis of the transmissibility change of NCP and its potential factors may provide a reliable reference for establishing effective prevention and control strategies. METHOD: By means of the method of calculating the instantaneous basic reproduction number R(0t) proposed by Cori et al. (2013), we use R(0t) to describe the transmissibility change of COVID-19 in China, 2019-2020. In addition, the Baidu Index (BDI) and Baidu Migration Scale (BMS) were selected to measure the public awareness and the effect of Wuhan lockdown (restricted persons in Wuhan outflow from the epidemic area) strategy, respectively. The Granger causality test (GCT) was carried out to explore the association between public awareness, the effect of the Wuhan lockdown strategy, and the transmissibility of COVID-19. RESULTS: The estimated averaged basic reproduction number of NCP in China was 3.44 with 95% CI (2.87, 4.0) during Dec. 8, 2019, to Feb. 9, 2020. The instantaneous basic reproduction numbers (R(0t)) have two waves and reaching peaks on Jan. 8 and Jan. 27, respectively. After reaching a peak on Jan. 27, R(0t) showed a continuous decline trend. On Feb. 9, R(0t) has fallen to 1.68 (95% CI: 1.66, 1.7), but it is still larger than 1. We find a significantly negative association between public awareness and the transmissibility change of COVID-19, with one unit increase in cumulative BDI leading to a decrease of 0.0295% (95% CI: 0.0077, 0.051) R(0t). We also find a significantly negative association between the effect of the Wuhan lockdown strategy and the transmissibility change of COVID-19, and a one unit decrease in BMS may lead to a drop of 2.7% (95% CI: 0.382, 4.97) R(0t). CONCLUSION: The current prevention and control measures have effectively reduced the transmissibility of COVID-19; however, R(0t) is still larger than the threshold 1. The results show that the government adopting the Wuhan lockdown strategy plays an important role in restricting the potential infected persons in Wuhan outflow from the epidemic area and avoiding a nationwide spread by quickly controlling the potential infection in Wuhan. Meanwhile, since Jan. 18, 2020, the people successively accessed COVID-19-related information via the Internet, which may help to effectively implement the government's prevention and control strategy and contribute to reducing the transmissibility of NCP. Therefore, ongoing travel restriction and public health awareness remain essential to provide a foundation for controlling the outbreak of COVID-19.


title: Immunoglobulin heavy chain diversity in Pteropid bats: evidence for a diverse and highly specific antigen binding repertoire

text: Bats are the natural host reservoir for range of emerging and re-emerging viruses, many of which cause significant morbidity and mortality in other mammals, yet appear to result in no clinical consequences for bats. The ability of bats to coexist with a variety of viruses presents an interesting immunological problem that has not been examined in any detail but which could provide significant insights into the evolution of antiviral mechanisms in mammals. Towards a better understanding of the bat immune system, we analysed the expressed heavy chain variable (VH) regions of antibodies from the black flying fox, Pteropus alecto. The germline repertoire of the closely related Pteropid bat, Pteropus vampyrus, whose genome has been sequenced was also examined for comparative purposes. Representative VH genes were found in all three mammalian VH clans (I, II and III) in both the expressed P. alecto VH repertoire and the germline P. vampyrus VH repertoire. Evidence for the use of multiple heavy chain diversity (DH) and joining (JH) segments for the generation of diverse VDJ rearrangements was also present in the expressed antibody repertoire of P. alecto. The long period of co-evolutionary history of bats with viruses may have resulted in a variety of highly specific VH segments being hardwired into the genomes of bats and may have implications for their ability to successfully cope with a diversity of viral antigens.


title: Citrus tristeza virus co-opts glyceraldehyde 3-phosphate dehydrogenase for its infectious cycle by interacting with the viral-encoded protein p23

text: KEY MESSAGE: Citrus tristeza virus encodes a unique protein, p23, with multiple functional roles that include co-option of the cytoplasmic glyceraldehyde 3-phosphate dehydrogenase to facilitate the viral infectious cycle. ABSTRACT: The genome of citrus tristeza virus (CTV), genus Closterovirus family Closteroviridae, is a single-stranded (+) RNA potentially encoding at least 17 proteins. One (p23), an RNA-binding protein of 209 amino acids with a putative Zn-finger and some basic motifs, displays singular features: (i) it has no homologues in other closteroviruses, (ii) it accumulates mainly in the nucleolus and Cajal bodies, and in plasmodesmata, and (iii) it mediates asymmetric accumulation of CTV RNA strands, intracellular suppression of RNA silencing, induction of some CTV syndromes and enhancement of systemic infection when expressed as a transgene ectopically or in phloem-associated cells in several Citrus spp. Here, a yeast two-hybrid screening of an expression library of Nicotiana benthamiana (a symptomatic experimental host for CTV), identified a transducin/WD40 domain protein and the cytosolic glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as potential host interactors with p23. Bimolecular fluorescence complementation corroborated the p23-GAPDH interaction in planta and showed that p23 interacts with itself in the nucleolus, Cajal bodies and plasmodesmata, and with GAPDH in the cytoplasm (forming aggregates) and in plasmodesmata. The latter interaction was preserved in a p23 deletion mutant affecting the C-terminal domain, but not in two others affecting the Zn-finger and one internal basic motif. Virus-induced gene silencing of GAPDH mRNA resulted in a decrease of CTV titer as revealed by real-time RT-quantitative PCR and RNA gel-blot hybridization. Thus, like other viruses, CTV seems to co-opt GAPDH, via interaction with p23, to facilitate its infectious cycle.


title: Comparison between dot-immunoblotting assay and clinical sign determination method for quantifying avian infectious bronchitis virus vaccine by titration in embryonated eggs

text: Abstract A sensitive and specific method for measuring the vaccine titer of infectious bronchitis virus (IBV) is important to commercial manufacturers for improving vaccine quality. Typically, IBV is titrated in embryonated chicken eggs, and the infectivity of the virus dilutions is determined by assessing clinical signs in the embryos as evidence of viral propagation. In this study, we used a dot-immunoblotting assay (DIA) to measure the titers of IBV vaccines that originated from different pathogenic strains or attenuation methods in embryonated eggs, and we compared this assay to the currently used method, clinical sign evaluation. To compare the two methods, we used real-time reverse transcription-PCR, which had the lowest limit of detection for propagated IBV. As a clinical sign of infection, dwarfism of the embryo was quantified using the embryo: egg (EE) index. The DIA showed 9.41% higher sensitivity and 15.5% higher specificity than the clinical sign determination method. The DIA was particularly useful for measuring the titer of IBV vaccine that did not cause apparent stunting but propagated in embryonated chicken eggs such as a heat-adapted vaccine strain. The results of this study indicate that the DIA is a rapid, sensitive, reliable method for determining IBV vaccine titer in embryonated eggs at a relatively low cost.


title: On a Comprehensive Model of the Novel Coronavirus (COVID-19) Under Mittag-Leffler Derivative

text: Abstract The major purpose of the presented study is to analyze and find the solution for the model of nonlinear fractional differential equations (FDEs) describing the deadly and most parlous virus so-called coronavirus (COVID-19). The mathematical model depending of fourteen nonlinear FDEs is presented and the corresponding numerical results are studied by applying the fractional Adams Bashforth (AB) method. Moreover, a recently introduced fractional nonlocal operator known as Atangana-Baleanu (AB) is applied in order to realize more effectively. For the current results, the fixed point theorems of Krasnoselskii and Banach are hired to present the existence, uniqueness as well as stability of the model. For numerical simulations, the behavior of the approximate solution is presented in terms of graphs through various fractional orders. Finally, a brief discussion on conclusion about the simulation is given to describe how the transmission dynamics of infection take place in society.


title: Ectopeptidases in pathophysiology

text: Ectopeptidases are transmembrane proteins present in a wide variety of tissues and cell types. Dysregulated expression of certain ectopeptidases in human malignancies suggests their value as clinical markers. Ectopeptidase interaction with agonistic antibodies or their inhibitors has revealed that these ectoenzymes are able to modulate bioactive peptide responses and to influence growth, apoptosis and differentiation, as well as adhesion and motility, all functions involved in normal and tumoral processes. There is evidence that ectopeptidase‐mediated signal transduction frequently involves tyrosine phosphorylation. Combined analyses of gene organization and regulation of ectopeptidases by various physiological factors have provided insights into their structure–function relationships. Understanding the roles of ectopeptidases in pathophysiology may have implications in considering them as therapeutic targets. BioEssays 23:251–260, 2001. © 2001 John Wiley & Sons, Inc.


title: New Approaches to Preventing, Diagnosing, and Treating Neonatal Sepsis

text: Karen Edmond and Anita Zaidi highlight new approaches that could reduce the burden of neonatal sepsis worldwide.


title: Innate Immunity: Introduction

text: The concept of ‘innate immunity’ embraces all sorts of measures that exclude, inhibit, or slow down infections with little specificity and without adaptation or generation of a protective memory. The mammalian innate immune defenses described in this article comprise the complement system, nonspecific phagocytic and cytolytic leukocytes (macrophages, monocytes, granulocytes, natural killer cells, and dendritic cells), and cytokines such as the antivirally active type I interferons. Since the type I interferon (IFN-α/β) system is our primary defense against viral infections, special attention will be paid to the virus-triggered induction of IFN transcription, the signaling activated by IFNs, and the antiviral factors expressed as a consequence.


Lung Ultrasound In The Frontline Diagnosis Of Covid-19 Infection


title: Capacity of Thailand to Contain an Emerging Influenza Pandemic

text: Southeast Asia will likely be the epicenter of the next influenza pandemic. To determine whether health system resources in Thailand are sufficient to contain an emerging pandemic, we mapped health system resources in 76 provinces. We used 3 prepandemic scenarios of clustered cases and determined resource needs, availability, and gaps. We extended this analysis to a scenario of a modest pandemic and assumed that the same standards of clinical care would be required. We found that gaps exist in many resource categories, even under scenarios in which few cases occur. Such gaps are likely to be profound if a severe pandemic occurs. These gaps exist in infrastructure, personnel and materials, and surveillance capacity. Policy makers must determine whether such resource gaps can realistically be closed, ideally before a pandemic occurs. Alternatively, explicit assumptions must be made regarding allocation of scarce resources, standards of care, and priority setting during a pandemic.


title: Chapter 14 Human Resources for Health

text: Abstract A health system is an expensive knowledge-based industry made up of professionals, paraprofessionals, and administrative and support personnel. Human resources to provide and manage public health and clinical services are crucial to developing and sustaining national and global health systems. High-income countries are replete with highly trained and motivated personnel, but face issues such as increasing costs of care for aging populations and using new categories of health workers. Low-income countries face severe human resource shortages as training programs are underdeveloped. Health workforce issues include urban–rural differentiation, promoting standards and quality of care, specialization versus primary care, tensions between public and private health systems, and integrating new health professions. Migration of health professionals from low-income to high-income countries hampers the buildup of a critical mass of leaders, providers, and teachers to expand the capacity of health systems. Strategic policies are crucial to this field.


title: Science in crisis

text: Amid the pandemic, a second epidemic of preliminary, unverified and misinterpreted research has broken out, reports Graham Lawton


title: Fear of COVID-19 Scale—Associations of Its Scores with Health Literacy and Health-Related Behaviors among Medical Students

text: The coronavirus disease 2019 (COVID-19) pandemic causes fear, as its immediate consequences for the public have produced unprecedented challenges for the education and healthcare systems. We aimed to validate the fear of COVID-19 scale (FCoV-19S) and examine the association of its scores with health literacy and health-related behaviors among medical students. A cross-sectional study was conducted from 7 to 29 April 2020 on 5423 students at eight universities across Vietnam, including five universities in the North, one university in the Center, two universities in the South. An online survey questionnaire was used to collect data on participants’ characteristics, health literacy, fear of COVID-19 using the FCoV-19S, and health-related behaviors. The results showed that seven items of the FCoV-19S strongly loaded on one component, explained 62.15% of the variance, with good item–scale convergent validity and high internal consistency (Cronbach’s alpha = 0.90). Higher health literacy was associated with lower FCoV-19S scores (coefficient, B, −0.06; 95% confidence interval, 95%CI, −0.08, −0.04; p < 0.001). Older age or last academic years, being men, and being able to pay for medication were associated with lower FCoV-19S scores. Students with higher FCoV-19S scores more likely kept smoking (odds ratio, OR, 1.11; 95% CI, 1.08, 1.14; p < 0.001) or drinking alcohol (OR, 1.04; 95% CI, 1.02, 1.06; p < 0.001) at an unchanged or higher level during the pandemic, as compared to students with lower FCoV-19S scores. In conclusion, the FCoV-19S is valid and reliable in screening for fear of COVID-19. Health literacy was found to protect medical students from fear. Smoking and drinking appeared to have a negative impact on fear of COVID-19. Strategic public health approaches are required to reduce fear and promote healthy lifestyles during the pandemic.


title: Chest CT features and their role in COVID-19

text: Abstract Since December 2019, the novel coronavirus disease (COVID-19) has spread rapidly throughout China. This article reviews the chest CT features of COVID-19 and analyzes the role of chest CT in this health emergency.


title: Chloroquine as prophylactic agent against COVID-19?

text: • Efficacy of hydroxychloroquine and chloroquine in COVID-19 treatment; • Use of hydroxychloroquine or chloroquine in COVID-19 prophylaxis.


title: Fear and Practice Modifications among Dentists to Combat Novel Coronavirus Disease (COVID-19) Outbreak

text: An outbreak of novel coronavirus disease (COVID-19) in China has influenced every aspect of life. Healthcare professionals, especially dentists, are exposed to a higher risk of getting infected due to close contact with infected patients. The current study was conducted to assess anxiety and fear of getting infected among dentists while working during the current novel coronavirus diseases (COVID-19) outbreak. In addition, dentists’ knowledge about various practice modifications to combat COVID-19 has been evaluated. A cross-sectional study was conducted using an online survey from 10th to 17th March 2020. The well-constructed questionnaire was designed and registered at online website (Kwiksurveys) and validated. A total of 669 participants from 30 different countries across the world responded. After scrutiny, completed questionnaires (n = 650) were included in the study. Statistical analysis was performed using SPSS version 25. Chi-Square and Spearman correlation tests were applied to control confounders and assess the relation of dentists’ response with respect to gender and educational level. More than two-thirds of the general dental practitioners (78%) from 30 countries questioned were anxious and scared by the devastating effects of COVID-19. A large number of dentists (90%) were aware of recent changes in the treatment protocols. However, execution of amended treatment protocol was recorded as 61%. The majority of the dentists (76%) were working in the hospital setting out of which 74% were from private, and 20% were from government setups. Individually we received a large number of responses from Pakistan and Saudi Arabia, but collectively more than 50% of the responses were from other parts of the world. Despite having a high standard of knowledge and practice, dental practitioners around the globe are in a state of anxiety and fear while working in their respective fields due to the COVID-19 pandemic impact on humanity. A number of dental practices have either modified their services according to the recommended guidelines to emergency treatment only or closed down practices for an uncertain period.


title: Case–control study of microbiological etiology associated with calf diarrhea

text: Abstract Calf diarrhea is a major economic burden for the US cattle industry. A variety of infectious agents are implicated in calf diarrhea and co-infection of multiple pathogens is not uncommon in diarrheic calves. A case–control study was conducted to assess infectious etiologies associated with calf diarrhea in Midwest cattle farms. A total of 199 and 245 fecal samples were obtained from diarrheic and healthy calves, respectively, from 165 cattle farms. Samples were tested by a panel of multiplex PCR assays for 11 enteric pathogens: bovine rotavirus group A (BRV-A), bovine coronavirus (BCoV), bovine viral diarrhea virus (BVDV), bovine enterovirus (BEV), bovine norovirus (BNoV), Nebovirus, bovine torovirus (BToV) Salmonella spp. (Salmonella), Escherichia coli (E. coli) K99+, Clostridium perfringens with β toxin gene and Cryptosporidium parvum (C. parvum). The association between diarrhea and detection of each pathogen was analyzed using a multivariate logistic regression model. More than a half of the fecal samples from the diarrheic calves had multiple pathogens. Statistically, BRV-A, BCoV, BNoV, Nebovirus, Salmonella, E. coli K99+, and C. parvum were significantly associated with calf diarrhea (p <0.05). Among them, C. parvum and BRV-A were considered to be the most common enteric pathogens for calf diarrhea with high detection frequency (33.7% and 27.1%) and strong odds ratio (173 and 79.9). Unexpectedly BNoV (OR=2.0) and Nebovirus (OR=16.7) were identified with high frequency in diarrheic calves, suggesting these viruses may have a significant contribution to calf diarrhea.


Utilizing technology as a method of contact tracing and surveillance to minimize the risk of contracting COVID-19 infection