title: The National Vaccine Advisory Committee at 30: Impact and opportunity

text: Abstract Thirty years after passage of legislation that created the National Vaccine Advisory Committee (NVAC) “to achieve optimal prevention of human infectious diseases through immunization and to achieve optimal prevention against adverse reactions to vaccines,” this review reflects NVAC’s role and impact on the U.S. vaccine and immunization enterprise as an external advisor to the Department of Health and Human Services. We reviewed the history of NVAC in the context of the principles of its establishment, with a focus on its reports and recommendations. We performed a systematic literature review to identify NVAC reports published in widely-accessible public health journals, and we reviewed the available archives to identify other reports and resolutions approved by the committee not published in journals. We characterized key issues considered by NVAC according to the five goals of the 2010 National Vaccine Plan. The predominance of NVAC activities to date related to the implementation of immunization across the lifespan and the many aspects of the system needed to foster the goal of full immunization. Reflecting on the impacts of NVAC to date, this review identified 30 NVAC approved reports published in journals, 22 stand-alone resolutions, and 26 unique unpublished reports. The development of new and improved vaccines continues to represent a significant priority for NVAC, and we identified several challenges related to future vaccine innovation. Given the many factors that impact on policy changes in the vaccine and immunization enterprise, we encountered challenges associated with demonstrating attribution of specific policy changes to NVAC recommendations. Although difficult to quantify, this review suggests that NVAC played an important role in the improvements in the U.S. immunization enterprise over the past 30 years and that NVAC can and will continue to play an important role supporting U.S. immunization going forward.


Considerations for scaling down fetal echocardiograms during the COVID-19 pandemic


Remdesivir bei Patienten mit COVID-19


title: Assessment of the risk of infectious aerosols leaking to the environment from BSL-3 laboratory HEPA air filtration systems using model bacterial aerosols

text: Abstract To assess the risk of infectious bacterial aerosols leaking to the environment, the filtration efficiency of a biosafety level 3 (BSL-3) laboratory high-efficiency particulate (HEPA) filter was investigated using the aerosolized bacteria Serratia marcescens. The aerosol size was measured using an Andersen sampler. Eight first stage HEPA filters (numbered 1–8) were distributed in contaminated labs and exhausts from each of the first stage HEPA filters were aggregated and filtered through one second stage HEPA filter before being released to the environment. In total, 8 first-stage and 1 second-stage HEPA filters from the BSL-3 air purification system were analyzed. No S. marcescens was detected in first stage filters 1, 2, 4, 5, 7 and 8 and the second stage HEPA filter. The filtration efficiencies against aerosolized S. marcescens were >99.9999%. First stage filter numbers 3 and 6 had filtration efficiencies of 99.9825% and 99.9906%, respectively. When filter number 3 was replaced by a new filter and the bracket for filter number 6 was sealed, no aerosolized S. marcescens was detected in the filtered air. Our work suggests that the BSL-3 laboratory HEPA filter air purification system is effective against bacterial aerosols, with little to no bacterial leakage into the environment.


title: Application of computational methods for anticancer drug discovery, design, and optimization

text: Abstract Developing a novel drug is a complex, risky, expensive and time-consuming venture. It is estimated that the conventional drug discovery process ending with a new medicine ready for the market can take up to 15 years and more than a billion USD. Fortunately, this scenario has recently changed with the arrival of new approaches. Many novel technologies and methodologies have been developed to increase the efficiency of the drug discovery process, and computational methodologies have become a crucial component of many drug discovery programs. From hit identification to lead optimization, techniques such as ligand- or structure-based virtual screening are widely used in many discovery efforts. It is the case for designing potential anticancer drugs and drug candidates, where these computational approaches have had a major impact over the years and have provided fruitful insights into the field of cancer. In this paper, we review the concept of rational design presenting some of the most representative examples of molecules identified by means of it. Key principles are illustrated through case studies including specifically successful achievements in the field of anticancer drug design to demonstrate that research advances, with the aid of in silico drug design, have the potential to create novel anticancer drugs.


title: Epidemic update of COVID-19 in Hubei Province compared with other regions in China

text: Abstract Aims & Background The COVID-19 outbreak spread in China and is a threat to the world. The aims of this study to help health workers better understand the epidemic of the COVID-19 and provide different control strategies toward Hubei Province and other regions in China. Methods A comprehensive search of the Chinese Center for Disease Control and Prevention official websites and announcements was performed between 20 Jan 2019 and 29 Feb 2020. The relevant data of the distribution of the infection on each reported day were obtained. Results& findings Up to 29 Feb 2020, 79,824 confirmed cases with the COVID-19 including 66,907 in Hubei Province and 12,377 in other administrative regions were reported. The SARS-COV-2 showed faster epidemic trends compared with the 2003-SARS-CoV. A total of 2,870 deaths have been reported nationwide among 79,824 confirmed cases, with a mortality of 3.6%. The mortality of the COVID-19 was significantly higher in Hubei Province than that in other regions(4.1% versus 0.84%). Since 1 Feb 2020 the number of discharged cases exceeded the number of the dead. By 29 Feb 2020, the number of discharged patients was 41,625, which exceeded the number of hospitalized patients, and the trend has further increased. Conclusions The infection of the SARS-COV-2 is spreading and increasing nationwide, and Hubei Province is the main epidemic area, with higher mortality. The outbreak is now under initial control especially in other regions outside of Hubei Province. Due to the different epidemic characteristics between Hubei Province and other regions, we should focus on different prevention and control strategies.


title: Regulation of the innate immune system by ubiquitin and ubiquitin-like modifiers

text: Abstract Detection of invading pathogens by pattern recognition receptors (PRRs) is crucial for the activation of the innate immune response. These sensors signal through intertwining signaling cascades which result in the expression of pro-inflammatory cytokines and type I interferons. Conjugation, or binding, of ubiquitin and ubiquitin-like modifiers (UBLs) to a plethora of immune signaling molecules forms a common theme in innate immune regulation. Numerous E3 ligases and deubiquitylating enzymes (DUBs) actively modify signaling components in order to achieve a balanced activation of the innate immune system. This review will discuss how this balance is achieved and which questions remain regarding innate immune regulation by ubiquitin and UBLs.


title: Radiographic severity index in COVID-19 pneumonia: relationship to age and sex in 783 Italian patients

text: PURPOSE: To improve the risk stratification of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an experimental chest X-ray (CXR) scoring system for quantifying lung abnormalities was introduced in our Diagnostic Imaging Department. The purpose of this study was to retrospectively evaluate correlations between the CXR score and the age or sex of Italian patients infected with SARS-CoV-2. MATERIALS AND METHODS: Between March 4, 2020, and March 18, 2020, all CXR reports containing the new scoring system were retrieved. Only hospitalized patients with SARS-CoV-2 infection were enrolled. For each patient, age, sex, and the CXR report containing the highest score were considered for the analysis. Patients were also divided into seven groups according to age. Nonparametric statistical tests were used to examine the relationship between the severity of lung disease and the age or sex. RESULTS: 783 Italian patients (532 males and 251 females) with SARS-CoV-2 infection were enrolled. The CXR score was significantly higher in males than in females only in groups aged 50 to 79 years. A significant correlation was observed between the CXR score and age in both males and females. Males aged 50 years or older and females aged 80 years or older with coronavirus disease 2019 showed the highest CXR score (median ≥ 8). CONCLUSIONS: Males aged 50 years or older and females aged 80 years or older showed the highest risk of developing severe lung disease. Our results may help to identify the highest-risk patients and those who require specific treatment strategies.


title: Expression of 9-O- and 7,9-O-acetyl modified sialic acid in cells and their effects on influenza viruses

text: Sialic acids (Sia) are widely displayed on the surfaces of cells and tissues. Sia come in a variety of chemically modified forms, including those with acetyl modifications at the C7, C8, and C9 positions. Here, we analyzed the distribution and amounts of these acetyl modifications in different human and canine cells. As Sia or their variant forms are receptors for influenza A and influenza C viruses, we examined the effects of these modifications on virus infections. We confirmed that 9-O-acetyl and 7,9-O-acetyl modified Sia are widely but variably expressed across cell lines from both humans and canines. While they were expressed on the cell surface of canine MDCK cell lines, they were located primarily within the Golgi compartment of human HEK-293 and A549 cells. The O-acetyl modified Sia were expressed at low levels of 1-2% of total Sia in these cell lines. We knocked out and over-expressed the sialate O-acetyltransferase gene (CasD1), and knocked out the sialate O-acetylesterase gene (SIAE) using CRISPR/Cas9 editing. Knocking out CasD1 removed 7,9-O- and 9-O-acetyl Sia expression, confirming previous reports. However, over-expression of CasD1 and knockout of SIAE gave only modest increases in 9-O-acetyl levels in cells and no change in 7,9-O-acetyl levels, indicating that there are complex regulations of these modifications. These modifications were essential for influenza C infection, but had no obvious effect on influenza A infection. Sialic acids are key glycans that are involved in many different normal cellular functions, as well as being receptors for many pathogens. However, Sia come in diverse chemically modified forms. Here we examined and manipulated the expression of 7,9-O- and 9-O-acetyl modified Sia on cells commonly used in influenza virus and other research by engineering the enzymes that produce or remove the acetyl groups.


title: Structural characterization of the fusion core in syncytin, envelope protein of human endogenous retrovirus family W

text: Abstract Syncytin is a captive retroviral envelope protein, possibly involved in the formation of the placental syncytiotrophoblast layer generated by trophoblast cell fusion at the maternal–fetal interface. We found that syncytin and type I viral envelope proteins shared similar structural profiling, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR). We expressed the predicted regions of NHR (41aa) and CHR (34aa) in syncytin as a native single chain (named 2-helix protein) to characterize it. 2-helix protein exists as a trimer and is highly α-helix, thermo-stable, and denatured by low pH. NHR and CHR could form a protease-resistant complex. The complex structure built by the molecular docking demonstrated that NHR and CHR associated in an antiparallel manner. Overall, the 2-helix protein could form a thermo-stable coiled coil trimer. The fusion core structure of syncytin was first demonstrated in endogenous retrovirus. These results support the explanation how syncytin mediates cytotrophoblast cell fusion involved in placental morphogenesis.


title: Genomics functional analysis and drug screening of SARS-CoV-2

text: Abstract A novel coronavirus appeared in Wuhan, China has led to major outbreaks. Recently, rapid classification of virus species, analysis of genome and screening for effective drugs are the most important tasks. In the present study, through literature review, sequence alignment, ORF identification, motif recognition, secondary and tertiary structure prediction, the whole genome of SARS-CoV-2 were comprehensively analyzed. To find effective drugs, the parameters of binding sites were calculated by SeeSAR. In addition, potential miRNAs were predicted according to RNA base-pairing. After prediction by using NCBI, WebMGA and GeneMark and comparison, a total of 8 credible ORFs were detected. Even the whole genome have great difference with other CoVs, each ORF has high homology with SARS-CoVs (>90%). Furthermore, domain composition in each ORFs was also similar to SARS. In the DrugBank database, only 7 potential drugs were screened based on the sequence search module. Further predicted binding sites between drug and ORFs revealed that 2-(N-Morpholino)-ethanesulfonic acid could bind 1# ORF in 4 different regions ideally. Meanwhile, both benzyl (2-oxopropyl) carbamate and 4-(dimehylamina) benzoic acid have bene demonstrated to inhibit SARS-CoV infection effectively. Interestingly, 2 miRNAs (miR-1307-3p and miR-3613-5p) were predicted to prevent virus replication via targeting 3′-UTR of the genome or as biomarkers. In conclusion, the novel coronavirus may have consanguinity with SARS. Drugs used to treat SARS may also be effective against the novel virus. In addition, altering miRNA expression may become a potential therapeutic schedule.


title: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review

text: BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.


title: Did the Pattern of Practice in the Prescription of Palliative Radiotherapy for the Treatment of Uncomplicated Bone Metastases Change between 1999 and 2005 at the Rapid Response Radiotherapy Program?

text: Abstract Aims Since 1999, randomised clinical trials and meta-analyses have reported equal efficacy of pain relief from single- and multiple-fraction radiotherapy for bone metastases. A number of factors, including limited radiotherapy resources, waiting times, and patient convenience, suggest single fraction to be the treatment of choice for patients. However, international patterns of practice indicate that multiple fractions are still commonly used. This study examined whether dose-fractionation schemes used for the treatment of bone metastases at the Rapid Response Radiotherapy Program (RRRP) at the Odette Cancer Centre have changed since 1999. Materials and methods A retrospective review of the prospective RRRP database and hospital records were conducted for all patients treated with palliative radiotherapy for uncomplicated bone metastases at the RRRP in 1999 (or baseline), 2001, 2004 and from 1 January to 31 July 2005. Data were collected on patient demographics and clinical characteristics. Results Of the 693 patients, 65 and 35% were prescribed single fraction (predominantly single 8Gy) and multiple fractions (predominantly 20Gy/five fractions), respectively. The administration of single treatments generally increased over time, from 51% in 1999 to 66% in 2005 (P =0.0001). On the basis of multiple logistic regression analyses, patients were more likely to be prescribed single-fraction radiotherapy if they had prostate cancer, had a poorer performance status, were treated to the limbs, hips, shoulders, pelvis, ribs, scapula, sternum, or clavicle (compared with the spine), were treated by a radiation oncologist who had been trained in earlier years, and who were treated after 1999. Conclusions Between 1999 and 2005, the use of single-fraction radiotherapy increased, corresponding to publications showing equal efficacy of pain relief between single and multiple fractions in the management of uncomplicated bone metastases. However, about a third of patients still received multiple fractions.


Critically ill SARS-CoV-2-infected patients are not stratified as sepsis by the qSOFA


title: Substrate specificity and phosphorylation of antiviral and anticancer nucleoside analogues by human deoxyribonucleoside kinases and ribonucleoside kinases

text: Abstract Structural analogues of nucleosides, nucleoside analogues (NA), are used in the treatment of cancer and viral infections. Antiviral NAs inhibit replication of the viral genome, whereas anticancer NAs inhibit cellular DNA replication and repair. NAs are inactive prodrugs that are dependent on intracellular phosphorylation to their pharmacologically active triphosphate form. The deoxyribonucleoside kinases (dNK) and ribonucleoside kinases (rNK) catalyze the first phosphorylation step, converting deoxyribonucleosides and ribonucleosides to their corresponding monophosphate form. The dNKs have been studied intensively, whereas the rNKs have not been as thoroughly investigated. This overview is focused on the substrate specificity, tissue distribution, and subcellular location of the mammalian dNKs and rNKs and their role in the activation of NAs.


title: Arms Race between Enveloped Viruses and the Host ERAD Machinery

text: Enveloped viruses represent a significant category of pathogens that cause serious diseases in animals. These viruses express envelope glycoproteins that are singularly important during the infection of host cells by mediating fusion between the viral envelope and host cell membranes. Despite low homology at protein levels, three classes of viral fusion proteins have, as of yet, been identified based on structural similarities. Their incorporation into viral particles is dependent upon their proper sub-cellular localization after being expressed and folded properly in the endoplasmic reticulum (ER). However, viral protein expression can cause stress in the ER, and host cells respond to alleviate the ER stress in the form of the unfolded protein response (UPR); the effects of which have been observed to potentiate or inhibit viral infection. One important arm of UPR is to elevate the capacity of the ER-associated protein degradation (ERAD) pathway, which is comprised of host quality control machinery that ensures proper protein folding. In this review, we provide relevant details regarding viral envelope glycoproteins, UPR, ERAD, and their interactions in host cells.


title: Human Antimicrobial Peptides as Therapeutics for Viral Infections

text: Successful in vivo infection following pathogen entry requires the evasion and subversion of multiple immunological barriers. Antimicrobial peptides (AMPs) are one of the first immune pathways upregulated during infection by multiple pathogens, in multiple organs in vivo. In humans, there are many classes of AMPs exhibiting broad antimicrobial activities, with defensins and the human cathelicidin LL-37 being the best studied examples. Whereas historically the efficacy and therapeutic potential of AMPs against bacterial infection has been the primary focus of research, recent studies have begun to elucidate the antiviral properties of AMPs as well as their role in regulation of inflammation and chemoattraction. AMPs as therapeutic tools seem especially promising against emerging infectious viral pathogens for which no approved vaccines or treatments are currently available, such as dengue virus (DENV) and Zika virus (ZIKV). In this review, we summarize recent studies elucidating the efficacy and diverse mechanisms of action of various classes of AMPs against multiple viral pathogens, as well as the potential use of human AMPs in novel antiviral therapeutic strategies.


Inflammatory bowel diseases and COVID-19: the invisible enemy


title: Remote Data Retrieval for Bioinformatics Applications: An Agent Migration Approach

text: Some of the approaches have been developed to retrieve data automatically from one or multiple remote biological data sources. However, most of them require researchers to remain online and wait for returned results. The latter not only requires highly available network connection, but also may cause the network overload. Moreover, so far none of the existing approaches has been designed to address the following problems when retrieving the remote data in a mobile network environment: (1) the resources of mobile devices are limited; (2) network connection is relatively of low quality; and (3) mobile users are not always online. To address the aforementioned problems, we integrate an agent migration approach with a multi-agent system to overcome the high latency or limited bandwidth problem by moving their computations to the required resources or services. More importantly, the approach is fit for the mobile computing environments. Presented in this paper are also the system architecture, the migration strategy, as well as the security authentication of agent migration. As a demonstration, the remote data retrieval from GenBank was used to illustrate the feasibility of the proposed approach.


title: Financial spillover and global risk in a multi-region model of the world economy()

text: This paper estimates a three-region DSGE model (EA, US, RoW) with international financial linkages in the form of cross-border equity holding and allowing for region-specific as well as global financial shocks, which match empirical measures of financial tightness and global stock market valuation. Spillover from financial shocks increases with international financial integration and is practically zero under full home bias in normal times. The global risk captures international synchronisation of financial cycles. Spillover of financial shocks is amplified at the zero lower bound, at which investment risk takes on the characteristics of a general uncertainty shock. The model results suggest that integrated financial markets should provide a powerful motivation for international policy coordination to prevent financial turmoil.


Notes from the Eye of the Storm: Trainees at the Frontlines of the COVID-19 Pandemic


Radiological Presentation of COVID19


Transmission of influenza A in human beings


title: Communication, collaboration and cooperation can stop the 2019 coronavirus

text: As the outbreak of a deadly new coronavirus in China and its rapid spread is rattling countries, only the collective international experience and advances derived from past outbreaks can accelerate its control.


title: Need for ensuring care for neuro-emergencies—lessons learned from the COVID-19 pandemic

text: BACKGROUND: To investigate whether patients with critical emergency conditions are seeking or receiving the medical care that they require, we characterized the reality of care for patients presenting with neuro-emergencies during the first phase of the COVID-19 pandemic. METHODS: In this observational, longitudinal cohort study, all neurosurgical admissions that presented to our department between February 1 and April 15 during the COVID-19 pandemic and during the same time period in 2019 were identified and categorized according to the presence of a neuro-emergency, the route of admission, management, and the category of disease. Further, the clinical course of patients with aneurysmal subarachnoid hemorrhage (aSAH) and chronic subdural hematoma (cSDH) was investigated representatively for severe vascular and semi-urgent traumatic conditions that present with a wide variety of symptoms. RESULTS: During the pandemic, the percentage of neuro-emergencies among all neurosurgical admissions remained similar but a larger proportion presented through the emergency department than through the outpatient clinic or by referral (*p = 0.009). The total number of neuro-emergencies was significantly reduced (*p = 0.0007) across all types of disease, particularly in vascular (*p = 0.036) but also in spinal (*p = 0.007) and hydrocephalus (*p = 0.048) emergencies. Patients with spinal emergencies presented 48 h later (*p = 0.001) despite comparable symptom severity. For aSAH, the number of cases, aSAH grade, aneurysm localization, and treatment modality did not change but strikingly, elderly patients with cSDH presented less frequently, with more severe symptoms (*p = 0.046), and were less likely to reach favorable outcome (*p = 0.003) at discharge compared with previous years. CONCLUSIONS: Despite pandemic-related restrictive measures and reallocation of resources, patients with neuro-emergencies should be encouraged to present regardless of the severity of symptoms because deferred presentation may result in adverse outcome. Thus, conservation of critical healthcare resources remains essential in spite of fighting COVID-19.


title: Chapter 17 Effective control of waterborne pathogens by aquatic plants

text: Abstract The role of aquatic plants in treating wastewater contaminated with inorganic and organic pollutants is well established. Recent studies have shown that aquatic plants possess potential to remove pathogens from wastewater. High removal (90%) of pathogenic microbes such as Enterococci, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Clostridium perfringens, Staphylococcus aureus, and Salmonella have been achieved using aquatic plant species viz. Typha latifolia, Cyperus papyrus, Cyperus alternifolius, Phragmites mauritianus, Pistia stratiotes, Lemna paucicostata, Spirodela polyrhiza, Eichhornia crassipes. Pathogen removal by aquatic plants mainly occurs because of toxicity exerted by exudates produced by them or attachment of pathogens to plant roots followed by filtration. Constructed wetlands have proved very efficient in treating pathogen-contaminated water. More studies are required to find out the exact mechanism of pathogen removal by these plants so that their role in phytoremediation technologies can be emphasized.


title: Triaging spine surgery and treatment during the COVID-19 pandemic

text: OBJECTIVE: To utilize evidence based medicine in determining which spinal surgeries are appropriate during the COVID-19 era. METHODS: A literature review was performed for articles discussing the indications for common procedures in spine surgery. Based on these indications, we sub-categorized these procedures into “elective” versus “urgent” versus “emergent” categories. RESULTS: Indications for spinal surgery were reviewed and determined to which may be considered emergent/urgent/elective. This manuscript presents a decision-making algorithm for determining the appropriateness of proceeding with spinal surgery during this COVID-19 time period. CONCLUSIONS: Spinal surgery during the COVID-19 pandemic is an intricate decision-making process, involving sociologic, clinical, and economic factors.


title: Seasonal influenza surveillance: Observational study on the 2017–2018 season with predominant B influenza virus circulation

text: Abstract Introduction Influenza is a common respiratory infectious disease affecting population worldwide yearly. The aim of this work is to describe the 2017–2018 influenza season and how it affected elderly population in Catalonia despite moderate vaccine coverage among this age group. Methods Influenza surveillance based on a primary care sentinel surveillance, virological indicators systematic sampling of ILI attended and severe influenza confirmed cases (SHLCI) admitted to hospital. Analysis of data by Chi-squared, ANOVA, multiple regression and negative control test or case to case for vaccine effectiveness assessment in primary care and SHLCI respectively. Results Moderate-high intensity and early onset season with predominance of influenza B virus (IVB) (63%) followed by an increase of circulation of influenza A virus (IVA). A total of 419 IV from primary care samples. Vaccine effectiveness (VE) in primary care setting was 14% (95%CI: 0–47%). 1306 severe cases (adjusted cumulative incidence 18.54/100,000 inhabitants (95%CI: 17.54–19.55)). The highest proportion of severe cases were in the >64 (65.1%) (aOR 15.70; 95%CI: 12.06–20.46; p <0.001) followed by 45–64yo (25.4%) (aOR 6.03; 95%CI: 4.57–7.97). VE in preventing intensive care unit (ICU) admission was 35% (95%CI: 10–54%). Final outcome death while hospitalized occurred in 175 SHLCI cases with a case fatality rate of 13.4%. Conclusions 2017–2018 influenza season was an unusual epidemic season with an early onset, great predominance of influenza B (Yamagata strain) virus with a high hospitalization rate of severe cases among elderly stressing the need to upgrade vaccine uptake in this age group.


title: Noninvasive Positive-Pressure Ventilation An Experimental Model to Assess Air and Particle Dispersion

text: Background Health-care workers are concerned about the risk of acquiring contagious diseases such as severe acute respiratory syndrome and avian influenza after recent outbreaks. We studied exhaled air and particle dispersion through an oronasal mask attached to a human-patient simulator (HPS) during noninvasive positive-pressure ventilation (NPPV). Methods Airflow was marked with intrapulmonary smoke for visualization. Therapy with inspiratory positive airway pressure (IPAP) was started at 10 cm H2O and gradually increased to 18 cm H2O, whereas expiratory positive airway pressure was maintained at 4 cm H2O. A leakage jet plume was revealed by a laser light sheet and images captured by video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. Findings A jet plume of air leaked through the mask exhaust holes to a radial distance of 0.25 m from the mask during the application of IPAP at 10 cm H2O with some leakage from the nasal bridge. The leakage plume exposure probability was highest about 60 to 80 mm lateral to the median sagittal plane of the HPS. Without nasal bridge leakage, the jet plume from the exhaust holes increased to a 0.40-m radius from the mask, whereas exposure probability was highest about 0.28 m above the patient. When IPAP was increased to 18 cm H2O, the vertical plume extended to 0.45 m above the patient with some horizontal spreading along the ward ceiling. Conclusion Substantial exposure to exhaled air occurs within a 0.5-m radius of patients receiving NPPV. Medical wards should be designed with an architectural aerodynamics approach and knowledge of air/particle dispersion from common mechanical ventilatory techniques.


Lay media reporting of monkeypox in Nigeria


title: Detection and molecular characterization of chicken astrovirus associated with chicks that have an unusual condition known as “white chicks” in Brazil

text: Chicken astrovirus (CAstV) is one of many viruses related to enteric diseases in poultry that are associated with Runting-Stunting Syndrome (RSS), which affects young chickens. CAstV was also recently associated with an unusual condition in chicks called “white chicks.” Some hatcheries in certain states of Brazil have reported several incubation problems, mortality, and the presence of chicks with white plumages over the past several months. These chicks were termed locally as “white chicks.” The present work investigated 30 chicks with this unusual condition using a multidisciplinary approach. Postmortem examination of each chick showed enlarged livers and intestines that were full of liquid and gas (30/30). The pancreas, kidneys, and spleen were pale (30/30). The other organs did not show any macroscopic alterations. CAstV, chicken parvovirus (ChPV), avian nephritis virus (ANV), avian rotavirus (ARtV), avian reovirus (AReoV), infectious bronchitis virus (IBV), and fowl adenovirus group I (FAdV-1) were tested in the intestines, pancreas, proventriculus, gizzard, liver, spleen, bursa, kidneys, thymus, lung, heart, brain, and yolk sac in each chick. All organs and yolk sacs were positive for CAstV in different titres and negative for the other tested viruses. The partial molecular characterization of the ORF 1b gene of CAstV using 28 sequences revealed a high similarity of the nucleotides and amino acids with sequences of CAstV from North America, Europe, and Asia, and our CAstV sequences clustered into a unique group that was separate from the other sequences. These results demonstrated that CAstV was associated with the white chick condition in Brazil. The virus was distributed in most organs, including the brain and yolk sac. These results suggest that the virus could be transmitted vertically. The molecular characterization also revealed that the CAstV associated with white chick condition was molecularly related to other CAstV sequences found worldwide.


title: Elevated serum levels of IL-6 and CXCL9 in autoimmune retinopathy (AIR) patients

text: Abstract Autoimmune retinopathy (AIR) is a rare immune-mediated retinopathy associated with circulating antiretinal antibodies (ARAs). Other prominent features of AIR include visual field deficits and photoreceptor dysfunction in the setting of progressive unexplained vision loss. The role of inflammation is poorly understood in AIR. Since cytokines play a central role in the initiation and development of inflammation, we evaluated the presence of proinflammatory cytokines and chemokines in AIR patient sera. We demonstrate that IL-6 and CXCL9 are both elevated in AIR patient sera. Moreover, the presence and concentration of these 2 molecules appear to correlate with AIR patient disease severity. This cytokine profile, IL-6 and CXCL9, has been described to participate in a variety of autoimmune and inflammatory diseases. Our study provides support for an activated inflammatory process in AIR and identifies possible mechanisms that can drive autoimmunity in this disease.


title: Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation

text: Coronaviruses induce in infected cells the formation of double membrane vesicles, which are the sites of RNA replication. Not much is known about the formation of these vesicles, although recent observations indicate an important role for the endoplasmic reticulum in the formation of the mouse hepatitis coronavirus (MHV) replication complexes (RCs). We now show that MHV replication is sensitive to brefeldin A (BFA). Consistently, expression of a dominant-negative mutant of ARF1, known to mimic the action of the drug, inhibited MHV infection profoundly. Immunofluorescence analysis and quantitative electron microscopy demonstrated that BFA did not block the formation of RCs per se, but rather reduced their number. MHV RNA replication was not sensitive to BFA in MDCK cells, which are known to express the BFA-resistant guanine nucleotide exchange factor GBF1. Accordingly, individual knockdown of the Golgi-resident targets of BFA by transfection of small interfering RNAs (siRNAs) showed that GBF1, but not BIG1 or BIG2, was critically involved in MHV RNA replication. ARF1, the cellular effector of GBF1, also appeared to be involved in MHV replication, as siRNAs targeting this small GTPase inhibited MHV infection significantly. Collectively, our results demonstrate that GBF1-mediated ARF1 activation is required for efficient MHV RNA replication and reveal that the early secretory pathway and MHV replication complex formation are closely connected.


title: Epidemiología de la sarcoidosis

text: La sarcoidosis es una enfermedad multisistémica que afecta frecuentemente al pulmón. Su incidencia y prevalencia han sido ampliamente estudiadas, pero la falta de estandarización del diagnóstico, los diferentes métodos de detección de casos y la escasa sensibilidad y especificidad de las pruebas diagnósticas explican los datos discordantes. El pronóstico es generalmente favorable. Gran parte de las personas afectadas no manifestarán nunca síntomas y muchas tienen remisión espontánea. El curso es crónico en el 10-30% de los casos, con un deterioro permanente de la función pulmonar. La enfermedad es el resultado de la acción de un agente externo que desencadena la respuesta inmunitaria característica en individuos genéticamente susceptibles. Se han implicado factores ambientales, ocupacionales y genéticos, pero las investigaciones están todavía en los inicios. Estudios de casos y controles, así como los avances en biología molecular, ayudarán a definir los factores de susceptibilidad genética y a entender los distintos fenotipos de la sarcoidosis. Sarcoidosis is a multisystemic disease in which lung involvement is common. Its incidence and prevalence have been extensively studied, but with contradictory results because of the lack of standard diagnostic criteria, variations in the methods for detecting cases, and the low sensitivity and specificity of diagnostic tests. Prognosis is generally favorable. Many of those affected remain asymptomatic and remission often occurs spontaneously, although between 10% and 30% of the patients have chronic disease and permanent deterioration in lung function. Sarcoidosis is caused by an external agent that triggers a characteristic immune response in genetically susceptible individuals. Environmental, occupational, and genetic factors have all been implicated, but research is still in the early stages. Case-control studies, as well as advances in molecular biology, will help to identify genetic susceptibility factors and to understand the different phenotypes of sarcoidosis.


Will COVID‐19 change how we prescribe?


title: Functional Nanomaterials Can Optimize the Efficacy of Vaccines

text: Nanoscale materials can improve the efficacy of vaccines. Herein we review latest developments that use nanomaterials for vaccines. By highlighting the relationships between the nanoscale physicochemical characteristics and working mechanisms of nanomaterials, this paper shows the current status of the developments where researchers employ functional nanomaterials as vector and/or immunoregulators for vaccines. It also provides us some clues for improving the design and application of nanomaterials to optimize the efficacy of vaccines.


title: Influenza surveillance in Europe: establishing epidemic thresholds by the Moving Epidemic Method

text: Please cite this paper as: Vega et al. (2012) Influenza surveillance in Europe: establishing epidemic thresholds by the moving epidemic method. Influenza and Other Respiratory Viruses 7(4), 546–558. Background Timely influenza surveillance is important to monitor influenza epidemics. Objectives (i) To calculate the epidemic threshold for influenza‐like illness (ILI) and acute respiratory infections (ARI) in 19 countries, as well as the thresholds for different levels of intensity. (ii) To evaluate the performance of these thresholds. Methods The moving epidemic method (MEM) has been developed to determine the baseline influenza activity and an epidemic threshold. False alerts, detection lags and timeliness of the detection of epidemics were calculated. The performance was evaluated using a cross‐validation procedure. Results The overall sensitivity of the MEM threshold was 71·8% and the specificity was 95·5%. The median of the timeliness was 1 week (range: 0–4·5). Conclusions The method produced a robust and specific signal to detect influenza epidemics. The good balance between the sensitivity and specificity of the epidemic threshold to detect seasonal epidemics and avoid false alerts has advantages for public health purposes. This method may serve as standard to define the start of the annual influenza epidemic in countries in Europe.


title: European Association of Urology Guidelines Office Rapid Reaction Group: An Organisation-wide Collaborative Effort to Adapt the European Association of Urology Guidelines Recommendations to the Coronavirus Disease 2019 Era()

text: The coronavirus disease 2019 (COVID-19) pandemic is unlike anything seen before by modern science-based medicine. Health systems across the world are struggling to manage it. Added to this struggle are the effects of social confinement and isolation. This brings into question whether the latest guidelines are relevant in this crisis. We aim to support urologists in this difficult situation by providing tools that can facilitate decision making, and to minimise the impact and risks for both patients and health professionals delivering urological care, whenever possible. We hope that the revised recommendations will assist urologist surgeons across the globe to guide the management of urological conditions during the current COVID-19 pandemic.


title: The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system

text: In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called “cytokine storm” an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.


title: Needs assessment for novel Gram-negative antibiotics in US hospitals: a retrospective cohort study

text: BACKGROUND: Evidence-based needs assessments for novel antibiotics against highly-resistant Gram-negative infections (GNIs) are scarce. We aimed to use real-world data from an electronic health record repository to identify treatment opportunities in US hospitals for GNIs resistant to all first-line drugs. METHODS: For this retrospective cohort study, population estimates with an unmet need for novel Gram-negative antibiotics were quantified using the Cerner Health Facts database (2009–15), aggregating episodes of infection in US hospitals with pathogens displaying difficult-to-treat resistance (DTR; resistance to carbapenems, other β-lactams, and fluoroquinolones) and episodes involving empirical coverage with reserve drugs (colistin or polymyxin B and aminoglycosides). Episodes displaying extended-spectrum cephalosporin resistance (ECR) were also estimated. Episodes were multiplied by site-specific and fixed 14-day treatment durations for conservative and liberal days-of-therapy (DOT) estimates and stratified by site and taxon. Hospital type-specific DOT rates were reliability adjusted to account for random variation; cluster analyses quantified contribution from outbreaks. FINDINGS: Across 2 996 271 inpatient encounters and 134 hospitals, there were 1352 DTR-GNI episodes, 1765 episodes involving empirical therapy with colistin or polymyxin B, and 16 632 episodes involving aminoglycosides. Collectively, these yielded 39·0 (conservative estimate) to 138·2 (liberal estimate) DOT per 10 000 encounters for a novel DTR-GNI-targeted drug, whereas greater treatment opportunities were identified for ECR (six times greater) and β-lactam susceptible GNIs (70 times greater). The most common DTR-GNI site and pathogen was lower respiratory (14·3 [43·3%] of 33 DOT per 10 000 encounters) and Pseudomonas aeruginosa (522 [38·1%] of 1371 episodes), whereas Enterobacteriaceae urinary-tract infections dominated the ECR or carbapenem-sparing niche (59·0% [5589 of 9535 episodes]) equating to 210·7 DOT per 10 000 encounters. DTR Stenotrophomonas maltophilia, Burkholderia spp, and Achromobacter spp represented less than 1 DOT per 10 000 encounters each. The estimated need for DTR-GNI-targeted antibiotics saw minor contributions by outbreaks and varied from 0·5 to 73·1 DOT per 10 000 encounters by hospital type. INTERPRETATION: Suspected or documented GNIs with no or suboptimal treatment options are relatively infrequent. Non-revenue-based strategies and innovative trial designs are probably essential to the development of antibiotics with improved effectiveness for these GNIs. FUNDING: Center for Drug Evaluation and Research, US Food and Drug Administration; Intramural Research Program, National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.


title: Recent advances in bioinorganic chemistry of bismuth

text: Bismuth has been used in medicine for over two centuries for the treatment of various diseases, in particular for gastrointestinal disorders, owing to its antimicrobial activity. Recent structural characterization of bismuth drugs provides an insight into assembly and pharmacokinetic pathway of the drugs. Mining potential protein targets inside the pathogen via metallomic/metalloproteomic approach and further characterization on the interactions of bismuth drugs with these targets laid foundation in understanding the mechanism of action of bismuth drugs. Such studies would be beneficial in rational design of new potential drugs.


title: Lung ultrasound imaging in avian influenza A (H7N9) respiratory failure

text: BACKGROUND: Lung ultrasound has been shown to identify in real-time, various pathologies of the lung such as pneumonia, viral pneumonia, and acute respiratory distress syndrome (ARDS). Lung ultrasound maybe a first-line alternative to chest X-ray and CT scan in critically ill patients with respiratory failure. We describe the use of lung ultrasound imaging and findings in two cases of severe respiratory failure from avian influenza A (H7N9) infection. METHODS: Serial lung ultrasound images and video from two cases of H7N9 respiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation in a tertiary care intensive care unit were analyzed for characteristic lung ultrasound findings described previously for respiratory failure and infection. These findings were followed serially, correlated with clinical course and chest X-ray. RESULTS: In both patients, characteristic lung ultrasound findings have been observed as previously described in viral pulmonary infections: subpleural consolidations associated or not with local pleural effusion. In addition, numerous, confluent, or coalescing B-lines leading to ‘white lung’ with corresponding pleural line thickening are associated with ARDS. Extension or reduction of lesions observed with ultrasound was also correlated respectively with clinical worsening or improvement. Coexisting consolidated pneumonia with sonographic air bronchograms was noted in one patient who did not survive. CONCLUSIONS: Clinicians with access to point-of-care ultrasonography may use these findings as an alternative to chest X-ray or CT scan. Lung ultrasound imaging may assist in the efficient allocation of intensive care for patients with respiratory failure from viral pulmonary infections, especially in resource scarce settings or situations such as future respiratory virus outbreaks or pandemics.


The Mental Health Impact of the COVID-19 Pandemic Across Different Cohorts


Alert to Potential Contagiousness: A Case of Lung Cancer with Asymptomatic SARS-CoV-2 Infection


title: Role of transcription regulatory sequence in regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus

text: In order to gain insight into the role of the transcription regulatory sequences (TRSs) in the regulation of gene expression and replication of porcine reproductive and respiratory syndrome virus (PRRSV), the enhanced green fluorescent protein (EGFP) gene, under the control of the different structural gene TRSs, was inserted between the N gene and 3′-UTR of the PRRSV genome and EGFP expression was analyzed for each TRS. TRSs of all the studied structural genes of PRRSV positively modulated EGFP expression at different levels. Among the TRSs analyzed, those of GP2, GP5, M, and N genes highly enhanced EGFP expression without altering replication of PRRSV. These data indicated that structural gene TRSs could be an extremely useful tool for foreign gene expression using PRRSV as a vector. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13567-017-0445-2) contains supplementary material, which is available to authorized users.


title: In silico studies on therapeutic agents for COVID-19: Drug repurposing approach

text: Abstract Aims The severe acute respiratory syndrome coronavirus 2, better known as COVID-19 has become the current health concern to the entire world. Initially appeared in Wuhan, China around December 2019, it had spread to almost 187 countries due to its high contagious nature. Precautionary measures remain the sole obliging tactic to cease the person to person transmissions till any effective method of treatment or vaccine is developed. Amidst the pandemic, research and development of new molecule is labour-intensive and tedious process. Drug repurposing is the concept of identifying therapeutically potent molecule from the library of pre-existing molecules. Materials and methods In the present study, 61 molecules that are already being used in clinics or under clinical scrutiny as antiviral agents are surveyed via docking study. Docking study was performed using Maestro interface (Schrödinger Suite, LLC, NY). Key findings Out of these 61 molecules, 37 molecules were found to interact with >2 protein structures of COVID-19. The docking results indicate that amongst the reported molecules, HIV protease inhibitors and RNA-dependent RNA polymerase inhibitors showed promising features of binding to COVID-19 enzyme. Along with these, Methisazone an inhibitor of protein synthesis, CGP42112A an angiotensin AT2 receptor agonist and ABT450 an inhibitor of the non-structural protein 3-4A might become convenient treatment option as well against COVID-19. Significance The drug repurposing approach provide an insight about the therapeutics that might be helpful in treating corona virus disease.


title: Sequencing and Computational Approaches to Identification and Characterization of Microbial Organisms

text: The recent advances in sequencing technologies and computational approaches are propelling scientists ever closer towards complete understanding of human-microbial interactions. The powerful sequencing platforms are rapidly producing huge amounts of nucleotide sequence data which are compiled into huge databases. This sequence data can be retrieved, assembled, and analyzed for identification of microbial pathogens and diagnosis of diseases. In this article, we present a commentary on how the metagenomics incorporated with microarray and new sequencing techniques are helping microbial detection and characterization.


title: Functional genomics in virology and antiviral drug discovery

text: Abstract Virology research and antiviral drug discovery are poised to benefit from the post-genomic revolution for three main reasons. First, viruses need the host to replicate and are therefore vulnerable to inhibition of cellular pathways. Knowledge of complete genomic sequences of both virus and host now permits the study of this interplay on a global scale. Combining transcriptomics and proteomics with large-scale gene knockdown experiments will enable the identification of novel antiviral targets. Second, massive parallel assay systems, such as DNA microarrays, which define the post-genomic era, will facilitate viral diagnostics. Third, the combination of genetics with genomics will enable the analysis of viral mutants and strains on an unprecedented scale. The dramatic effects of viral infection on host cell transcriptional patterns have been well-documented and will be briefly highlighted. In addition, we discuss recent trends that apply functional genomics methods to the discovery of new targets and therapies for viral disease.


Perinatal mental health and COVID‐19 in Japan


title: Invasion of the raccoon dog Nyctereutes procyonoides in Europe: History of colonization, features behind its success, and threats to native fauna

text: We aimed to review the history of the introduction and colonization of the raccoon dog Nyctereutes procyonoides in Europe, the features behind its successful expansion and its impact on native fauna. The raccoon dog quickly colonized new areas after being introduced to the European part of the former Soviet Union. Today it is widespread in Northern and Eastern Europe and is still spreading in Central Europe. Features behind its success include its adaptability, high reproductive potential, omnivory, hibernation in northern areas, multiple introductions with > 9000 individuals from different localities, and tendency to wander enabling gene flow between populations. Firm evidence of the raccoon dog’s negative impact on native fauna, such as a reduction in bird populations, is still scarce. Raccoon dogs may destroy waterfowl nests, although a nest predation study in Latvia did not confirm this. Predator removal studies in Finland suggested that the raccoon dog’s impact on game birds is smaller than expected. However, raccoon dogs may have caused local extinction of frog populations, especially on islands. Raccoon dogs may compete with other carnivores for food, for example for carrion in winter, or for the best habitat patches. In northern Europe potential competitors include the red fox Vulpes vulpes and the badger Meles meles, but studies of their diets or habitat preferences do not indicate severe competition. The raccoon dog is an important vector of diseases and parasites, such as rabies, Echinococcus multilocularis and Trichinella spp. and this is no doubt the most severe consequence arising from the spread of this alien species in Europe.


title: Prospect and application of Internet of Things technology for prevention of SARIs

text: Abstract The Internet of Things (IoT) includes three core procedures: full spectrum perception, reliable transmission, and intelligent processing. It can be applied for the prevention and control of SARI (severe acute respiratory infection). By combining sensors, information technology, artificial intelligence, and available dynamic networking devices, IoT could realize long-distance communication between hospitals, patients, and medical devices, which could ultimately improve current medical conditions.


title: Characterization of ubiquitin and ubiquitin-like-protein isopeptidase activities

text: Conjugation or deconjugation of ubiquitin (Ub) or ubiquitin-like proteins (UBLs) to or from cellular proteins is a multifaceted and universal means of regulating cellular physiology, controlling the lifetime, localization, and activity of many critical proteins. Deconjugation of Ub or UBL from proteins is performed by a class of proteases called isopeptidases. Herein is described a readily quantifiable novel isopeptidase assay platform consisting of Ub or UBL fused to the reporter enzyme phospholipase A(2) (PLA(2)). Isopeptidase activity releases PLA(2), which cleaves its substrate, generating a signal that is linear with deubiquitylase (DUB) concentration and is able to discriminate DUB, deSUMOylase, deNEDDylase, and deISGylase activities. The power and sensitivity of the UBL-PLA(2) assay are demonstrated by its ability to differentiate the contrasting deISGylase and DUB activities of two coronavirus proteases: severe acute respiratory syndrome papain-like protease (SARS-CoV PLpro) and NL63 CoV papain-like protease 2 (PLP2). Furthermore, direct comparisons with the current Ub-7-amino-4-methylcoumarin (Ub-AMC) assay demonstrated that the Ub-PLA(2) assay is an effective tool for characterizing modulators of isopeptidase activity. This observation was expanded by profiling the inhibitory activity of the nonselective isopeptidase inhibitor NSC 632839 against DUBs and deSUMOylases. Taken together, these studies illustrate the utility of the reporter-based approach to measuring isopeptidase activity.


What does the peripheral blood tell you in SARS?


title: New Technologies: Ethics of Genomics

text: Abstract Genomics, as a branch of genetics, uses Genome-Wide Association Studies and Whole-Genome Sequencing approaches to investigate how molecular structure, haplotype variation, and gene–environment complexity affect geno- and phenotypes, and invoke other life science system studies and -omics. Genomic medicine is quantitatively different from genetics, using variants as markers for diagnosis, prognosis, and prevention, as well as targets for treatment. Public Health Genomics extends these studies into population-wide variation and their impact on evidence-based policy, health systems, and health delivery and resources. The clinical significance of public health genomics will grow as sequencing becomes possible with low error rates, using better analytical methods that signal which variants are clinically significant, and the development of technologies that allow long-term stability of data storage. The most promising technologies cannot fully realize their potential if the relevant policy, legal, and regulatory issues are not adequately addressed.


title: SARS coronavirus 7a protein blocks cell cycle progression at G0/G1 phase via the cyclin D3/pRb pathway

text: Abstract The genome of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) contains four structural genes that are homologous to genes found in other coronaviruses, and also contains six subgroup-specific open reading frames (ORFs). Expression of one of these subgroup-specific genes, ORF7a, resulted in apoptosis via a caspase-dependent pathway. Here, we observed that transient expression of ORF7a protein fused with myc or GFP tags at its N or C terminus inhibited cell growth and prevented BrdU incorporation in different cultural cells, suggesting that ORF7a expression may regulate cell cycle progression. Analysis by flow cytometry demonstrated that ORF7a expression was associated with blockage of cell cycle progression at G0/G1 phase in HEK 293 cells after 24 to 60 h post-transfection. Similar results were observed in COS-7 and Vero cells. Mutation analysis of ORF7a revealed that the domain spanning aa 44–82 of 7a protein was essential for its cytoplasmic localization and for induction of the cell cycle arrest. After analyzing the cellular proteins involving in regulation of cell cycle progression, we demonstrated that ORF7a expression was correlated with a significant reduction of cyclin D3 level of mRNA transcription and expression, and phosphorylation of retinoblastoma (Rb) protein at ser795 and ser809/811, not with the expression of cyclin D1, D2, cdk4 and cdk6 in HEK 293 cells. These results suggest that the insufficient expression of cyclin D3 may cause a decreased activity of cyclin D/cdk4/6, resulting in the inhibition of Rb phosphorylation. Accumulation of hypo- or non-phosphorylated pRb thus prevents cell cycle progression at G0/G1 phase.


title: A bi-objective home healthcare routing and scheduling problem considering patients’ satisfaction in a fuzzy environment

text: Abstract Home care services are an alternative answer to hospitalization, and play an important role in reducing the healthcare costs for governments and healthcare practitioners. To find a valid plan for these services, an optimization problem called the home healthcare routing and scheduling problem is motivated to perform the logistics of the home care services. Although most studies mainly focus on minimizing the total cost of logistics activities, no study, as far as we know, has treated the patients’ satisfaction as an objective function under uncertainty. To make this problem more practical, this study proposes a bi-objective optimization methodology to model a multi-period and multi-depot home healthcare routing and scheduling problem in a fuzzy environment. With regards to a group of uncertain parameters such as the time of travel and services as well as patients’ satisfaction, a fuzzy approach named as the Jimenez’s method, is also utilized. To address the proposed home healthcare problem, new and well-established metaheuristics are obtained. Although the social engineering optimizer (SEO) has been applied to several optimization problems, it has not yet been applied in the healthcare routing and scheduling area. Another innovation is to develop a new modified multi-objective version of SEO by using an adaptive memory strategy, so-called AMSEO. Finally, a comprehensive discussion is provided by comparing the algorithms based on multi-objective metrics and sensitivity analyses. The practicality and efficiency of the AMSEO in this context lends weight to the development and application of the approach more broadly.


title: Don't adapt, shape! Use the crisis to shape your minimum viable system – And the wider market

text: Abstract In addition to being resilient and adaptive, firms should also utilize shocks such as COVID-19 to generate new business opportunities. Two processes make markets and other economic systems more malleable during times of crises: (1) as the stasis of the market system is interrupted, it forces the system “into movement” - and it requires less effort to nudge an already moving system in a specific direction; and (2) as deeply-rooted mental models are challenged during crises, any market-shaping initiative which promises a credible end to current instability with a new equilibrium will appeal to the natural human craving for stability. This malleability, in turn, creates multiple opportunities for firms to shape their markets and hence drive the market's development in favorable directions. We outline a generic process of market-shaping, comprising eight steps: (1) determining whether to act now or actively wait, (2) deciding whether to be a shaper or a supporter, (3) developing a scalable vision for the future market, (4) recognizing the minimum viable system linked to this vision, (5) driving changes in market-level properties, (6) securing that value is quantified and shared, (7) inviting actor engagement for implementation, and (8) defending against possible retaliations from threatened market systems.


title: Knowledge, attitudes, risk perceptions, and practices of adults toward COVID-19: a population and field-based study from Iran

text: OBJECTIVES: To determine peoples’ knowledge, attitudes, risk perceptions, and practices to provide policymakers pieces of field-based evidence and help them in the management of the COVID-19 epidemic. METHODS: This population-based survey was conducted using multi-stage stratified and cluster sampling in Shiraz, Iran. A total of 1331 persons were interviewed. The questionnaires were completed by face-to-face interviews. Univariable and multivariable (linear regression) data analyses were done using SPSS. RESULTS: The participants answered 63% of questions regarding knowledge, and 78% of questions regarding practice correctly. Only, 4.8% knew about common symptoms of COVID-19 and 7.3% about warning signs that require referral to hospitals. Males, lower educated people, and elders had a lower level of knowledge and poorer practices. Knowledge was also lower in the marginalized (socially deprived) people. Knowledge and practices’ correlation was 37%. Overall, 43.6% considered themselves at high risk of COVID-19, and 50% considered it as a severe disease. This disease had negative effects on most participants’ routine activities (69.1%). The participants preferred to follow the news from the national TV/Radio, social networks, and foreign satellite channels, respectively. CONCLUSIONS: Encouragement of people to observe preventive measures and decreasing social stress, especially among males, lower educated people, elders, and marginalized groups, are highly recommended.


title: Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy

text: BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56–75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5–11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60–99), with median PaO(2)/FiO(2) ratio, 267 (IQR 184–314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4–16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.


title: Molecular Distance to Health Transcriptional Score and Disease Severity in Children Hospitalized With Community-Acquired Pneumonia

text: Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP. Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization. Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1–1.07] and 1.12 [1.04–1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01–1.22]). Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.


Telemedicina aplicada a COVID-19


title: Insomnia and Stress of Physicians during COVID-19 Outbreak

text: Abstract Background Healthcare workers are at high risk of developing sleep disorders during an outbreak. This study aimed to measure severity of sleep difficulty and its correlation with duration of deal with suspected/confirmed cases of novel coronavirus (COVID-19) in physicians. Methods In this cross-sectional study, 268 physicians from different medical settings were included during the COVIS-19 outbreak. Results The mean age and experience of physicians were 35.06 (33-70 years) and 10.13 years. The median duration of dealing with suspected/confirmed cases of COVID-19 was 1.0 (0-30 days). The mean sleep score and stress of physicians were 8.43 of 24.0 and 4.20 of 10, respectively. More than two-thirds of the physicians were sleepless (68.3%) and majority had stress (93.7%). The study did not find a significant difference in sleep score of physicians with different specialties (P=0.059). However, most physicians were sleepless; including anesthesia and intensive care (77.8%); general physicians (80.8%), and obstetrics and gynecology (80.0%). They were sleepless in morning (58.7%); evening (77.8%); night (100%); and multi-shift (70.9%). The physicians who dealt with suspected or confirmed cases of COVID-19 or with stress had more escalated sleep compared to those who did not deal with patients or without stress (9.39 vs. 7.17 and 8.78 vs. 2.69 P<0.001). The sleep of physicians was escalated with increasing stress (r=0.558; P<0.001) and a number of days that physicians dealt with suspected/confirmed cases of COVID-19 (r=0.210; P=0.001), respectively. Conclusion The study confirmed that working with COVID-19 patients has a negative effect on the sleep of physicians.


title: Vaccines: Shaping global health

text: Abstract The Developing Countries Vaccine Manufacturers’ Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines’ access, and of the importance of new public-private partnerships.


title: Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

text: Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33, PLAUR, VEGF, IL13, CHI3L1, TSLP, GSDMB, TGFB1, POSTN, ESR1 and ARG2. In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function (i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.


title: Entrada del virus de la inmunodeficiencia humana en las células: mecanismos y posibilidades terapéuticas

text: La entrada del virus de la inmunodeficiencia humana (VIH) en la célula es la primera etapa del ciclo de replicación viral y una diana clave en la exploración de nuevos antirretrovirales. El mejor conocimiento de los mecanismos que se suceden con la entrada del VIH en las células que infecta ha permitido el desarrollo de moléculas que bloquean cada una de las etapas de la entrada vírica: unión de gp120 al receptor CD4; unión de gp120 a los correceptores de quimiocinas CCR5 y CXCR4, y fusión de las membranas viral y celular. Los inhibidores de la entrada del VIH son la última generación de antirretrovirales, de los cuales la enfuvirtida, un inhibidor de la fusión, ha sido el primero en comercializarse. Varios más se encuentran actualmente en fases avanzadas de desarrollo clínico y es de esperar que pronto contribuirán a mejorar el arsenal terapéutico frente al VIH. Human immunodeficiency virus (HIV) entry into cells is the first step in the viral replication cycle; which has been explored as a new therapeutic target; A better knowledge of the mechanisms involved in the entry process has led to the development of agents; which may inhibit each of the different steps of the viral entry process: attachment of the gp120 to the CD4 cell receptor; binding of the gp120 to CCR5 or CXCR4 coreceptors; and the fusion of viral and cell membranes; Entry inhibitors are the latest family of antiretroviral compounds; being enfuvirtide; a fusion inhibitor; the first approved; Several other entry inhibitors are currently in clinical development and hopefully soon will be part of the therapeutic armamentarium against HIV


title: Physiologic and fit factor profiles of N95 and P100 filtering facepiece respirators for use in hot, humid environments

text: BACKGROUND: To determine if hot, humid ambient conditions impact filtering facepiece respirators' (FFRs') fit, and to evaluate differences in physiologic and subjective responses between N95 FFRs and P100 FFRs. METHODS: Twelve subjects had physiologic monitoring and subjective perceptions monitored over 1 hour of treadmill exercise (5.6 km/h) in an environmental chamber (35°C, relative humidity 50%) wearing an N95 FFR, P100 FFR, or no respirator. Respirator quantitative fit testing was done before and after exercise. RESULTS: There was no significant difference in pass rates for both FFRs on initial fit testing, but subjects who passed were more likely to fail the postexercise test with N95 FFRs (P = .01). Wearing FFRs increased the temperature of facial skin covered by the FFR (P = .009) and breathing discomfort (P = .002). No significant differences were noted in other measured variables (heart rate, respiratory rate, oxygen saturation, transcutaneous carbon dioxide level, rectal temperature, global skin temperature, core temperature, and subjective perceptions) between controls and FFRs and between FFR models. CONCLUSION: After 1 hour of exercise in hot, humid ambient conditions, P100 FFRs retained better fit than N95 FFRs, without additional physiologic or subjective impact. Wearing FFRs under these conditions does not add to the body's thermophysiologic or perceptual burdens.


Disseminated intravascular coagulation in patients with 2019‐nCoV pneumonia


title: Jordan Field Epidemiology Training Program: Critical Role in National and Regional Capacity Building

text: Field Epidemiology Training Programs (FETPs) are 2-year training programs in applied epidemiology, established with the purpose of increasing a country’s capacity within the public health workforce to detect and respond to health threats and develop internal expertise in field epidemiology. The Jordan Ministry of Health, in partnership with the US Centers for Disease Control and Prevention, started the Jordan FETP (J-FETP) in 1998. Since then, it has achieved a high standard of success and has been established as a model for FETPs in the Eastern Mediterranean Region. Here we describe the J-FETP, its role in building the epidemiologic capacity of Jordan’s public health workforce, and its activities and achievements, which have grown the program to be self-sustaining within the Jordan Ministry of Health. Since its inception, the program’s residents and graduates have assisted the country to improve its surveillance systems, including revising the mortality surveillance policy, implementing the use of electronic data reporting, investigating outbreaks at national and regional levels, contributing to noncommunicable disease research and surveillance, and responding to regional emergencies and disasters. J-FETP’s structure and systems of support from the Jordan Ministry of Health and local, regional, and international partners have contributed to the success and sustainability of the J-FETP. The J-FETP has contributed significantly to improvements in surveillance systems, control of infectious diseases, outbreak investigations, and availability of reliable morbidity and mortality data in Jordan. Moreover, the program has supported public health and epidemiology in the Eastern Mediterranean Region. Best practices of the J-FETP can be applied to FETPs throughout the world.


title: Immunodeficiency risk score for prediction of mortality by parainfluenza virus infection in patients with hematologic malignancy

text: Parainfluenza virus (PIV) infection is a significant cause of morbidity and mortality, especially in hematologic malignancy patients including hematopoietic stem cell transplantation (HCT) recipients. However, limited information is available for risk stratification in PIV-infected patients with hematologic malignancy with or without HCT. Patients with hematologic malignancy diagnosed with PIV from January 2009 to December 2018 were retrospectively included in a tertiary care hospital in Seoul, South Korea. Upper respiratory tract infection (URTI) was defined as the detection of PIV in a nasopharyngeal sample with URTI symptoms without new pulmonary infiltrates. Lower respiratory tract infection (LRTI) was defined as detection of PIV in either upper or lower respiratory tract samples with new pulmonary infiltrates, with or without hypoxia. PIV-associated mortality was defined as death with respiratory failure and persistent LRTI within 90 days after diagnosis. The study included 143 adult patients. Of these, 55 (38%) progressed to or initially presented with LRTI. Among these, 22 (40%) died from PIV-associated mortality. An immunodeficiency risk score was developed from associated risk factors using a multivariable Cox regression model. Patients were stratified into low (0–2), moderate (3–5), and high risk (6–8) groups with PIV-associated mortalities of 0%, 9%, and 67%, respectively (p < 0.005, Harrell’s C-index = 0.84). PIV infection can result in substantial mortality in patients with hematologic malignancy if it progresses to LRTI. The immunodeficiency risk score presented here may be useful for distinguishing moderate and high risk groups that might benefit from antiviral therapy.


title: Sensitized Detection of Inhibitory Fragments and Iterative Development of Non‐Peptidic Protease Inhibitors by Dynamic Ligation Screening

text: A potential anti‐SARS drug has been developed by dynamic ligation screening (DLS), by which nucleophilic fragments are directed to the protein's active site by reversible reaction with an aldehyde inhibitor. Their inhibitory effect is detected by competition with a fluorogenic enzyme substrate. With this concept, low‐affinity fragments binding specifically to the active site are quickly identified in a functional enzyme assay.[Image: see text]


SARS Epidemic in the Press


title: Prevention of otitis media caused by viral upper respiratory tract infection: Vaccines, antivirals, and other approaches

text: Otitis media (OM) imposes significant morbidity on the pediatric age group and a large financial burden on the general population. Because standard medical treatments are not highly efficacious in resolving the accompanying middle ear (ME) inflammation, a goal of current research is OM prevention. Past studies show that new episodes of OM are usually a complication of viral upper respiratory infection (vURI), and therefore, a rational approach to achieving that goal is to develop intervention strategies that target vURIassociated OM. However, past experiences with antibiotics show that, in the absence of well-defined treatment protocols that maximize expected efficacy, the adoption of prophylactic or active treatments for OM can have negative consequences for the patient and for the general population. In this review, we discuss the hypothesized mechanisms by which a vURI is translated into an acute OM episode and describe different strategies for aborting that process. Limitations to deployment of each strategy are outlined.


Rhinovirus as a cause of fatal lower respiratory tract infection in adult stem cell transplantation patients: a report of two cases


title: Factors associated with prolonged viral shedding and impact of Lopinavir/Ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection

text: BACKGROUND: The duration of viral shedding is central to guide the decisions of isolation precautions and antiviral treatment. However, studies regarding the risk factors associated with prolonged SARS-CoV-2 shedding and the impact of Lopinavir/Ritonavir (LPV/r) treatment on viral shedding remain scarce. METHODS: Data were collected from all SARS-CoV-2 infected patients who were admitted to isolation wards and had reverse transcription polymerase chain-reaction conversion at the No.3 People's Hospital of Hubei province between 31 January and 09 March 2020. We compared clinical characteristics and SARS-CoV-2 RNA shedding between patients initiated with LPV/r treatment and those without. Logistic regression analysis was employed to evaluate the risk factors associated with prolonged viral shedding. RESULTS: Of 120 patients, the median age was 52 years, 54 (45%) were male and 78 (65%) received LPV/r treatment. The median duration of SARS-CoV-2 RNA detection from symptom onset was 23 days (IQR, 18–32 days). Older age (odd ratio [OR] 1.03, 95% confidence interval [CI] 1.00–1.05, p=0.03) and the lack of LPV/r treatment (OR 2.42, 95% CI 1.10–5.36, p=0.029) were independent risk factors of prolonged SARS-CoV-2 RNA shedding. Patients who initiated LPV/r treatment within 10 days from symptom onset, but not initiated from day 11 onwards, had significantly shorter viral shedding duration compared with those without LPV/r treatment (median 19 days versus 28.5 days, Log-rank p<0.001). CONCLUSION: Older age and the lack of LPV/r treatment were independently associated with prolonged SARS-CoV-2 RNA shedding in patients with COVID-19. Earlier administration of LPV/r treatment could shorten viral shedding duration.


title: Severe acute respiratory syndrome (SARS) and coronavirus disease-2019 (COVID-19): From causes to preventions in Hong Kong

text: Abstract Hong Kong has been recently attacked by the coronavirus disease-2019 (COVID-19). In late January 2020, it's shown a steadily increasing trend of confirmed cases. There is a 257 in total infected cases confirmed including 4 deaths until 20th of March 2020. To prevent further outbreak of COVID-19, this article discusses the current understanding of COVID-19 and compares with the outbreak of SARS-CoV-2 in 2003 of Hong Kong from the causes, transmission, symptoms, diagnosis, treatments and preventions to study for an applicable measurement to control COVID-19.


title: COVID-19 in Africa: care and protection for frontline healthcare workers

text: Medical staff caring for COVID-19 patients face mental stress, physical exhaustion, separation from families, stigma, and the pain of losing patients and colleagues. Many of them have acquired SARS-CoV-2 and some have died. In Africa, where the pandemic is escalating, there are major gaps in response capacity, especially in human resources and protective equipment. We examine these challenges and propose interventions to protect healthcare workers on the continent, drawing on articles identified on Medline (Pubmed) in a search on 24 March 2020. Global jostling means that supplies of personal protective equipment are limited in Africa. Even low-cost interventions such as facemasks for patients with a cough and water supplies for handwashing may be challenging, as is ‘physical distancing’ in overcrowded primary health care clinics. Without adequate protection, COVID-19 mortality may be high among healthcare workers and their family in Africa given limited critical care beds and difficulties in transporting ill healthcare workers from rural to urban care centres. Much can be done to protect healthcare workers, however. The continent has learnt invaluable lessons from Ebola and HIV control. HIV counselors and community healthcare workers are key resources, and could promote social distancing and related interventions, dispel myths, support healthcare workers, perform symptom screening and trace contacts. Staff motivation and retention may be enhanced through carefully managed risk ‘allowances’ or compensation. International support with personnel and protective equipment, especially from China, could turn the pandemic’s trajectory in Africa around. Telemedicine holds promise as it rationalises human resources and reduces patient contact and thus infection risks. Importantly, healthcare workers, using their authoritative voice, can promote effective COVID-19 policies and prioritization of their safety. Prioritizing healthcare workers for SARS-CoV-2 testing, hospital beds and targeted research, as well as ensuring that public figures and the population acknowledge the commitment of healthcare workers may help to maintain morale. Clearly there are multiple ways that international support and national commitment could help safeguard healthcare workers in Africa, essential for limiting the pandemic’s potentially devastating heath, socio-economic and security impacts on the continent.


title: Monitoring tourism flows and destination management: Empirical evidence for Portugal

text: We propose the use of a tool recently introduced by Gayer (2010), known as the “economic climate tracer”, to analyze and monitor the cyclical evolution of tourism source markets to Portugal. Considering the period 1987–2015, we evaluate how tourism to Portugal has been affected by economic cycles. This tool is useful as it clearly illustrates the evolutionary patterns of different markets, and allows us to identify close relationships with economic fluctuations. We found that German tourism plays a leading role, since its movements are followed with delays by tourism flows from other countries, and exhibits higher resilience to shocks. Also, domestic and Spanish tourism have both displayed less irregular behaviors than tourism from other source markets. On the contrary, tourism from the Netherlands and the UK, have displayed irregular patterns, which demonstrates the urgency to diversify tourism source markets to reduce the country's vulnerability to external shocks and economic cycles.


title: Reservoir Host Immune Responses to Emerging Zoonotic Viruses

text: Zoonotic viruses, such as HIV, Ebola virus, coronaviruses, influenza A viruses, hantaviruses, or henipaviruses, can result in profound pathology in humans. In contrast, populations of the reservoir hosts of zoonotic pathogens often appear to tolerate these infections with little evidence of disease. Why are viruses more dangerous in one species than another? Immunological studies investigating quantitative and qualitative differences in the host-virus equilibrium in animal reservoirs will be key to answering this question, informing new approaches for treating and preventing zoonotic diseases. Integrating an understanding of host immune responses with epidemiological, ecological, and evolutionary insights into viral emergence will shed light on mechanisms that minimize fitness costs associated with viral infection, facilitate transmission to other hosts, and underlie the association of specific reservoir hosts with multiple emerging viruses. Reservoir host studies provide a rich opportunity for elucidating fundamental immunological processes and their underlying genetic basis, in the context of distinct physiological and metabolic constraints that contribute to host resistance and disease tolerance.


Managing Type 2 Diabetes Mellitus during COVID‐19 Pandemic: The Bittersweet


title: Genotyping coronavirus SARS-CoV-2: Methods and implications

text: Abstract The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.


Aboriginal Community Controlled Health Organisations are taking a leading role in COVID‐19 health communication


title: Recovery from COVID‐19 in two patients with coexisted HIV infection

text: COVID‐19 has become a global health concern. HIV‐infected patients are particularly vulnerable to COVID‐19 due to their immune‐compromised status. The clinical manifestations and clinical outcomes of these patients are not clear. In this report, we presented two special COVID‐19 patients with HIV infection and other comorbidities. We described the clinical characteristics, clinical manifestations, treatments and clinical outcomes of both patients. One patient with prior HIV‐infection continued anti‐HIV treatment when diagnosed with COVID‐19. The other patient was newly diagnosed with HIV‐infection when diagnosed with COVID‐19 and had not begun anti‐HIV treatment. Both patients were treated with anti‐viral, antibiotics, oxygen treatment and supportive care and recovered from severe pneumonia. The experience of these two cases suggested that COVID‐19 patients with HIV infection could still have satisfactory clinical outcomes following proper medical care. This article is protected by copyright. All rights reserved.


title: The use of equine influenza pseudotypes for serological screening

text: Standard assays used for influenza serology present certain practical issues, such as inter-laboratory variability, complex protocols and the necessity for handling certain virus strains in high biological containment facilities. In an attempt to address this, avian and human influenza HA pseudotyped retroviruses have been successfully employed in antibody neutralization assays. In this study we generated an equine influenza pseudotyped lentivirus for serological screening. This was achieved by co-transfection of HEK293T cells with plasmids expressing the haemagglutinin (HA) protein of an H3N8 subtype equine influenza virus strain, HIV gag-pol and firefly luciferase reporter genes and harvesting virus from supernatant. In order to produce infective pseudotype particles it was necessary to additionally co-transfect a plasmid encoding the TMPRSS2 endoprotease to cleave the HA. High titre pseudotype virus (PV) was then used in PV antibody neutralization assays (PVNAs) to successfully distinguish between vaccinated and non-vaccinated equines. The sera were also screened by single radial haemolysis (SRH) assay. There was a 65% correlation between the results of the two assays, with the PVNA assay appearing slightly more sensitive. Future work will extend the testing of the PVNA with a larger number of serum samples to assess sensitivity/specificity, inter/intra-laboratory variability and to define a protective titre.