title: Antiviral Chemotherapy

text: Over the past 20 years, antiviral therapy has undergone a revolution and is now making a significant impact on the treatment of major virus diseases, for example HIV and viral hepatitis B and C. Targets include viral reverse transcriptases and proteases. The use of interferon to boost host immunity has also proved effective. Our understanding of chemotherapeutic strategies and drug resistance has become considerably more sophisticated since the widespread introduction of routine genome sequencing of virus isolates.


title: Point-of-Care Microdevices for Blood Plasma Analysis in Viral Infectious Diseases

text: Each year, outbreaks of viral infections cause illness, disability, death, and economic loss. As learned from past incidents, the detrimental impact grows exponentially without effective quarantine. Therefore, rapid on-site detection and analysis are highly desired. In addition, for high-risk areas of viral contamination, close monitoring should be provided during the potential disease incubation period. As the epidemic progresses, a response protocol needs tobe rapidly implemented and the virus evolution fully tracked. For these scenarios, point-of-care microdevices can provide sensitive, accurate, rapid and low-cost analysis for a large population, especially in handling complex patient samples, such as blood, urine and saliva. Blood plasma can be considered as a mine of information containing sources and clues of biomarkers, including nucleic acids, immunoglobulin and other proteins, as well as pathogens for clinical diagnosis. However, blood plasma is also the most complicated body fluid. For targeted plasma biomarker detection or untargeted plasma biomarker discovery, the challenges can be as difficult as identifying a needle in a haystack. A useful platform must not only pursue single performance characteristics, but also excel at multiple performance parameters, such as speed, accuracy, sensitivity, selectivity, cost, portability, reliability, and user friendliness. Throughout the decades, tremendous progress has been made in point-of-care microdevices for viral infectious diseases. In this paper, we review fully integrated lab-on-chip systems for blood analysis of viral infectious disease.


Letter: Implementation of a Neurosurgery Telehealth Program Amid the COVID-19 Crisis—Challenges, Lessons Learned, and a Way Forward


Reply to “MRI evaluation of the olfactory clefts in patients with SARS-CoV-2 infection revealed an unexpected mechanism for olfactory function loss”


title: Shortlisting SARS‐CoV‐2 Peptides for Targeted Studies from Experimental Data‐Dependent Acquisition Tandem Mass Spectrometry Data

text: Detection of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is a crucial tool for fighting the COVID‐19 pandemic. This dataset brief presents the exploration of a shotgun proteomics dataset acquired on SARS‐CoV‐2 infected Vero cells. Proteins from inactivated virus samples were extracted, digested with trypsin, and the resulting peptides were identified by data‐dependent acquisition tandem mass spectrometry. The 101 peptides reporting for six viral proteins were specifically analyzed in terms of their analytical characteristics, species specificity and conservation, and their proneness to structural modifications. Based on these results, a shortlist of 14 peptides from the N, S, and M main structural proteins that could be used for targeted mass‐spectrometry method development and diagnostic of the new SARS‐CoV‐2 is proposed and the best candidates are commented. This article is protected by copyright. All rights reserved


title: Chemokine CXCL14 is associated with prognosis in patients with colorectal carcinoma after curative resection

text: BACKGROUND: The chemokine CXCL14 has been reported to play an important role in the progression of many malignancies such as breast cancer and papillary thyroid carcinoma, but the role of CXCL14 in colorectal carcinoma (CRC) remains to be established. The purpose of this study was to investigate the expression pattern and significance of CXCL14 in CRC progression. METHOD: 265 colorectal carcinoma specimens and 129 matched adjacent normal colorectal mucosa specimens were collected. Expression of CXCL14 in clinical samples was examined by immunostaining. The effect of CXCL14 on colorectal carcinoma cell proliferation was measured by MTT assay, BrdU incorporation assay and colony formation assay. The impact of CXCL14 on migration and invasion of colorectal carcinoma cells was determined by transwell assay and Matrigel invasion assay, respectively. RESULTS: CXCL14 expression was significantly up-regulated in tumor tissues compared with adjacent nontumorous mucosa tissues (P < 0.001). Tumoral CXCL14 expression levels were significantly correlated with TNM (Tumor-node-metastasis) stage, histodifferentiation, and tumor size. In multivariate Cox regression analysis, high CXCL14 expression in tumor specimens (n = 91) from stage I/II patients was associated with increased risk for disease recurrence (risk ratio, 2.92; 95% CI, 1.15-7.40; P = 0.024). Elevated CXCL14 expression in tumor specimens (n = 135) from stage III/IV patients correlated with worse overall survival (risk ratio, 3.087; 95% CI, 1.866-5.107; P < 0.001). Functional studies demonstrated that enforced expression of CXCL14 in SW620 colorectal carcinoma cells resulted in more aggressive phenotypes. In contrast, knockdown of CXCL14 expression could mitigate the proliferative, migratory and invasive potential of HCT116 colorectal carcinoma cells. CONCLUSION: Taken together, CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a potential target of postoperative adjuvant therapy in CRC patients.


To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.


Visualisation of epidemiological map using an Internet of Things infectious disease surveillance platform


title: Early‐stage predictors of the acute phase duration in uncomplicated COVID‐19 pneumonia

text: OBJECTIVE: In this study, we aimed to highlight the common early‐stage clinical and laboratory variables independently related to the acute phase duration in patients with uncomplicated coronavirus disease (COVID‐19) pneumonia. METHODS: In hospitalized patients, the acute phase disease duration was followed using the Brescia‐COVID respiratory severity scale (BCRSS). Noninvasive ventilation was administered based on clinical judgment. Patients requiring oropharyngeal intubation were excluded from the study. For parameters to be measured at the hospital entrance, age, clinical history, National Early Warning Score2 (NEWS2, a multiparametric score system), partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F ratio), C‐reactive protein, and blood cell count were selected. RESULTS: In 64 patients, age (direct relationship), P/F, and platelet number (inverse relationship) independently accounted for 43% of the acute phase duration of the disease (p<0.001). CONCLUSIONS: For the first time, the present results revealed that the acute phase duration of non‐complicated pneumonia, resulting from severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is independently predicted from a patient's age, as well as based on the hospital entrance values of P/F ratio and peripheral blood platelet count. This article is protected by copyright. All rights reserved.


title: What’s really ‘Happning’? A forensic analysis of Android and iOS Happn dating apps

text: With today’s world revolving around online interaction, dating applications (apps) are a prime example of how people are able to discover and converse with others that may share similar interests or lifestyles, including during the recent COVID-19 lockdowns. To connect the users, geolocation is often utilized. However, with each new app comes the possibility of criminal exploitation. For example, while apps with geolocation feature are intended for users to provide personal information that drive their search to meet someone, that same information can be used by hackers or forensic analysts to gain access to personal data, albeit for different purposes. This paper examines the Happn dating app (versions 9.6.2, 9.7, and 9.8 for iOS devices, and versions 3.0.22 and 24.18.0 for Android devices), which geographically works differently compared to most notable dating apps by providing users with profiles of other users that might have passed by them or in the general radius of their location. Encompassing both iOS and Android devices along with eight varying user profiles with diverse backgrounds, this study aims to explore the potential for a malicious actor to uncover the personal information of another user by identifying artifacts that may pertain to sensitive user data.


title: Chapter 29 Role of Immune and Autoimmune Dysfunction in Schizophrenia

text: Abstract In this chapter, we review data in support of the concept that immune system dysregulation is the most plausible explanation that reconciles gene by environmental interactions in schizophrenia. Early investigations of this topic demonstrated aspects of aberrant activation of humoral immunity, including autoimmunity, associated with schizophrenia, whereas current research efforts have expanded this theme to include elements of innate immunity. Advances in our understanding of inflammation and molecules of both the adaptive and innate immune system and their functional roles in standard brain physiology provide an important context by which schizophrenia might arise as the result of the coupling of immune and neurodevelopmental dysregulation.


title: A phase trial of the oral Lactobacillus casei vaccine polarizes Th2 cell immunity against transmissible gastroenteritis coronavirus infection

text: Transmissible gastroenteritis coronavirus (TGEV) is a member of the genus Coronavirus, family Coronaviridae, order Nidovirales. TGEV is an enteropathogenic coronavirus that causes highly fatal acute diarrhoea in newborn pigs. An oral Lactobacillus casei (L. casei) vaccine against anti-transmissible gastroenteritis virus developed in our laboratory was used to study mucosal immune responses. In this L. casei vaccine, repetitive peptides expressed by L. casei (specifically the MDP and tuftsin fusion protein (MT)) were repeated 20 times and the D antigenic site of the TGEV spike (S) protein was repeated 6 times. Immunization with recombinant Lactobacillus is crucial for investigations of the effect of immunization, such as the first immunization time and dose. The first immunization is more important than the last immunization in the series. The recombinant Lactobacillus elicited specific systemic and mucosal immune responses. Recombinant L. casei had a strong potentiating effect on the cellular immunity induced by the oral L. casei vaccine. However, during TGEV infection, the systemic and local immune responses switched from Th1 to Th2-based immune responses. The systemic humoral immune response was stronger than the cellular immune response after TGEV infection. We found that the recombinant Lactobacillus stimulated IL-17 expression in both the systemic and mucosal immune responses against TGEV infection. Furthermore, the Lactobacillus vaccine stimulated an anti-TGEV infection Th17 pathway. The histopathological examination showed tremendous potential for recombinant Lactobacillus to enable rapid and effective treatment for TGEV with an intestinal tropism in piglets. The TGEV immune protection was primarily dependent on mucosal immunity.


title: Surveillance of Airborne Adenovirus and Mycoplasma pneumoniae in a Hospital Pediatric Department

text: This investigation evaluated the distributions of airborne adenovirus and Mycoplasma pneumoniae in public areas in the pediatric department of Children's Hospital in northern Taiwan. The airborne viral and bacterial concentrations were evaluated twice a week for a year using filter sampling with an airflow rate of 12 liters per minute for eight hours in the pediatric outpatient department and 24 hours in the pediatric emergency room. Real-time polymerase chain reaction assays were conducted for analysis. Approximately 18% of the air samples from the pediatric emergency room were found to contain adenovirus. Approximately forty-six percent of the air samples from the pediatric outpatient department contained Mycoplasma pneumoniae DNA products. High detection rates of airborne adenovirus DNA were obtained in July and August in the pediatric public areas. Airborne Mycoplasma pneumoniae was detected only in July in the pediatric emergency room and the peak levels were found from August to January in the pediatric outpatient department. Airborne particles that contained adenovirus and Mycoplasma pneumoniae were the most prevalent in the pediatric public areas. The potential relationship between these airborne viral/bacterial particles and human infection should be examined further. Keywords: adenovirus; Mycoplasma pneumoniae; filter sampling; real-time polymerase chain reaction; hospital; pediatric public areas.


title: Evaluation of a potential reintroduction of nuclear energy in Italy to accelerate the energy transition

text: Abstract Nuclear energy was adopted in Italy in the past to deal with the insufficient fossil fuels on the national territory. After a public vote subsequent to the Chernobyl accident, Italy abandoned the use of nuclear energy and nowadays adopts a mix of fossil fuels and renewable energy sources for electricity production. However, the urging environmental pollution and climate change issues are forcing Italy to realize a so-called “energy transition” towards a more sustainable energy production and consumption system. In this framework, following the examples of other countries, it could be re-evaluated the adoption of nuclear to reduce the consumption of fossil fuels. In the present paper, it is presented an overview of the nuclear energy history in Italy and the current and projected electricity demand and supply. Then, with reference to the Italian framework and policies, the main advantages and disadvantages of a hypothetical reintroduction of nuclear energy are presented. The analysis shows that the adoption of nuclear energy would bring several advantages in terms of lower emissions, higher security of supply and enabling of possible other technologies; the main disadvantages are related to the opposing public opinion and the nuclear waste management.


title: Prioritizing and Analyzing the Role of Climate and Urban Parameters in the Confirmed Cases of COVID-19 Based on Artificial Intelligence Applications

text: Nowadays, an infectious disease outbreak is considered one of the most destructive effects in the sustainable development process. The outbreak of new coronavirus (COVID-19) as an infectious disease showed that it has undesirable social, environmental, and economic impacts, and leads to serious challenges and threats. Additionally, investigating the prioritization parameters is of vital importance to reducing the negative impacts of this global crisis. Hence, the main aim of this study is to prioritize and analyze the role of certain environmental parameters. For this purpose, four cities in Italy were selected as a case study and some notable climate parameters—such as daily average temperature, relative humidity, wind speed—and an urban parameter, population density, were considered as input data set, with confirmed cases of COVID-19 being the output dataset. In this paper, two artificial intelligence techniques, including an artificial neural network (ANN) based on particle swarm optimization (PSO) algorithm and differential evolution (DE) algorithm, were used for prioritizing climate and urban parameters. The analysis is based on the feature selection process and then the obtained results from the proposed models compared to select the best one. Finally, the difference in cost function was about 0.0001 between the performances of the two models, hence, the two methods were not different in cost function, however, ANN-PSO was found to be better, because it reached to the desired precision level in lesser iterations than ANN-DE. In addition, the priority of two variables, urban parameter, and relative humidity, were the highest to predict the confirmed cases of COVID-19.


title: Factors Associated with Psychosis among Patients with Severe Acute Respiratory Syndrome: A Case-Control Study

text: We observed that a number of patients with severe acute respiratory syndrome (SARS) developed affective psychosis during the acute phase of their illness. We reviewed all SARS-related psychiatric consultations in Hong Kong and investigated the risk factors for psychosis among patients with SARS in a matched case-control study. Patients with SARS-related psychosis received higher total doses of steroids and had higher rates of family history of psychiatric illness. The findings of the present study suggest that steroid toxicity, personal vulnerability, and, probably, psychosocial stressors jointly contributed to the development of psychosis in patients with SARS.


title: Nanomedicine in Non-Small Cell Lung Cancer: From Conventional Treatments to Immunotherapy

text: Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related mortality. The heterogeneous nature of this disease hinders its diagnosis and treatment, requiring continuous advances in research aiming to understand its intricate nature. Consequently, the retrospective analysis of conventional therapies has allowed the introduction of novel tools provided by nanotechnology, leading to considerable improvements in clinical outcomes. Furthermore, the development of novel immunotherapies based on the recently understood interaction of the immune system with the tumor highlights the real possibility of definitively treating NSCLC from its early stages. Novel engineering approaches in nanomedicine will enable to overcome the intrinsic limits of conventional and emerging therapies regarding off-site cytotoxicity, specificity, resistance mechanisms, and administration issues. The convergence point of these therapies with nanotechnology lays the foundation for achieving currently unmet needs.


title: Establishment of the key Technical Indicators of Positive Pressure Biological Protective Clothing

text: Abstract Objective Trying to establish the key technical indicators related to positive pressure biological protective clothing (PPBPC), providing technical support for the establishment of PPBPC standards in the future. Method We examined the protection standard systems established by the major standards organizations in China and other developed countries. We also analyzed the technical indicators of the gas-tight chemical protective clothing and ventilated protective clothing against particulate radioactive contamination which closely related to PPBPC. And tested the performance of a set of imported dual-purpose PPBPC to verify the fit of its technical indicators with the standards. We aimed to identify the status of China’s standards in the area of personnel protection and put forward feasible suggestions for the production of PPBPC in China. Results Developed countries in Europe and North America have a complete system of standard protective clothing. China should also strengthen the construction of standard protective clothing, especially PPBPC. Conclusion With the improvements in infectious disease prevention and control on a global scale, the demand for PPBPC continues to increase and consideration should be given to the establishment of standards for this.


title: Behavior of the PR Interval with Increasing Heart Rate in Patients with COVID-19

text: BACKGROUND: Myriad manifestations of cardiovascular involvement are described in Coronavirus disease 2019 (COVID-19) but there have been no reports of COVID-19 affecting the cardiac conduction system. The PR interval on the electrocardiogram (ECG) normally shortens with increasing heart rate (HR). We encountered a COVID-19 patient manifesting Mobitz 1 atrioventricular (AV) block which normalized as he improved, prompting us to investigate PR interval behavior in COVID-19. OBJECTIVES: To characterize PR interval behavior in hospitalized COVID-19 patients, and correlate with clinical outcomes. METHODS: This study was a cross-sectional cohort analysis of confirmed COVID-19 cases (March 26–April 25, 2020). We reviewed pre-COVID-19 and COVID-19 ECGs to characterize AV conduction by calculating the PR interval to HR (PR:HR) slope. Clinical endpoints were death or need for endotracheal intubation. RESULTS: ECGs from 75 patients (246 pre-COVID-19 ECGs and 246 COVID-19 ECGs) were analyzed for PR:HR slope. Of these, 38 patients (50.7%) showed the expected PR interval shortening with increasing HR (negative PR:HR slopes), whereas 37 patients (49.3%) showed either no change (8 with PR:HR slopes=0) or paradoxical PR interval prolongation (29 with positive PR:HR slopes) with increasing HR. Patients without PR interval shortening were more likely to die (11/37, 29.7% vs. 3/38, 7.9%, P=0.019) or require endotracheal intubation (16/37, 43.2% vs. 8/38, 21.1%, P=0.05) compared to patients with PR interval shortening. CONCLUSION: Half of COVID-19 patients showed abnormal PR interval behavior (paradoxical prolongation or lack of shortening) with increasing HR. This finding was associated with increased risk of death and need for endotracheal intubation.


title: Astroviruses

text: Publisher Summary Human astroviruses are members of the Astroviridae family. They are non-enveloped viruses possessing a single-stranded RNA of positive polarity as their genome. The development of sensitive tests for the presence of astrovirus—for example, using group reactive monoclonal antibodies—has led to the conclusion that astroviruses are the cause of more cases of childhood diarrhea. Astroviruses have also been identified as the cause of major outbreaks of diarrhea and vomiting. Different serotypes of human astrovirus have been defined based on immune electron microscopy, neutralization tests, and type-specific enzyme immune assays (EIAs). Eight different serotypes have been identified and it has been shown that differences in the sequences of reverse transcription–polymerase chain reactions (RT-PCR) products from a region within open reading frame 2 (ORF2) correlated precisely with antigenic types determined by type-specific EIA.


title: Investigation of antiviral state mediated by interferon-inducible transmembrane protein 1 induced by H9N2 virus and inactivated viral particle in human endothelial cells

text: BACKGROUND: Endothelial cells are believed to play an important role in response to virus infection. Our previous microarray analysis showed that H9N2 virus infection and inactivated viral particle inoculation increased the expression of interferon-inducible transmembrane protein 1 (IFITM1) in human umbilical vein endothelial cells (HUVECs). In present study, we deeply investigated the expression patterns of IFITM1 and IFITM1-mediated antiviral response induced by H9N2 virus infection and inactivated viral particle inoculation in HUVECs. Epithelial cells that are considered target cells of the influenza virus were selected as a reference control. METHODS: First, we quantified the expression levels of IFITM1 in HUVECs induced by H9N2 virus infection or viral particle inoculation using quantitative real-time PCR and western blot. Second, we observed whether hemagglutinin or neuraminidase affected IFITM1 expression in HUVECs. Finally, we investigated the effect of induced-IFITM1 on the antiviral state in HUVECs by siRNA and activation plasmid transfection. RESULTS: Both H9N2 virus infection and viral particle inoculation increased the expression of IFITM1 without elevating the levels of interferon-ɑ/β in HUVECs. HA or NA protein binding alone is not sufficient to increase the levels of IFITM1 and interferon-ɑ/β in HUVECs. IFITM1 induced by viral particle inoculation significantly decreased the virus titers in culture supernatants of HUVECs. CONCLUSIONS: Our results showed that inactivated viral particle inoculation increased the expression of IFITM1 at mRNA and protein levels. Moreover, the induction of IFITM1 expression mediated the antiviral state in HUVECs.


title: Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza Part II: Future compounds against influenza virus

text: In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories.


Community–Based Epidemic Prevention in Taiwan: Combating the Coronavirus Disease–2019 Crisis


title: Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study

text: BACKGROUND: Rhinovirus (RV) associated early wheezing has been recognized as an independent risk factor for asthma. The risk is more important than that associated with respiratory syncytial virus (RSV) disease. No comparative data are available on the immune responses of these diseases. OBJECTIVE: To compare T-helper(1 )(Th(1)), Th(2 )and T-regulatory (T(reg)) cell type cytokine responses between RV and RSV induced early wheezing. METHODS: Systemic Th(1)-type (interferon [IFN] -gamma, interleukin [IL] -2, IL-12), Th(2)-type (IL-4, IL-5, IL-13) and T(reg)-type (IL-10) cytokine responses were studied from acute and convalescence phase serum samples of sole RV (n = 23) and RSV affected hospitalized wheezing children (n = 27). The pre-defined inclusion criteria were age of 3-35 months and first or second wheezing episode. Analysis was adjusted for baseline differences. Asymptomatic children with comparable demographics (n = 11) served as controls for RV-group. RESULTS: RV-group was older and had more atopic characteristics than RSV-group. At acute phase, RV-group had higher (fold change) IL-13 (39-fold), IL-12 (7.5-fold), IFN-gamma (6.0-fold) and IL-5 (2.8-fold) concentrations than RSV-group and higher IFN-gamma (27-fold), IL-2 (8.9-fold), IL-5 (5.6-fold) and IL-10 (2.6-fold) than the controls. 2-3 weeks later, RV-group had higher IFN-gamma (>100-fold), IL-13 (33-fold) and IL-10 (6.5-fold) concentrations than RSV-group and higher IFN-gamma (15-fold) and IL-2 (9.4-fold) than the controls. IL-10 levels were higher in acute phase compared to convalescence phase in both infections (p < 0.05 for all). CONCLUSION: Our results support a hypothesis that RV is likely to trigger wheezing mainly in children with a predisposition. IL-10 may have important regulatory function in acute viral wheeze.


title: The SpineBox: A Freely Available, Open-access, 3D-printed Simulator Design for Lumbar Pedicle Screw Placement

text: Background The recent COVID-19 pandemic has demonstrated the need for innovation in cost-effective and easily produced surgical simulations for trainee education that are not limited by physical confines of location. This can be accomplished with the use of desktop three-dimensional (3D) printing technology. This study describes the creation of a low-cost and open-access simulation for anatomical learning and pedicle screw placement in the lumbar spine, which is termed the SpineBox. Materials and methods An anonymized CT scan of the lumbar spine was obtained and converted into 3D software files of the L1-L5 vertebral bodies. A computer-assisted design (CAD) software was used to assemble the vertebral models into a simulator unit in anatomical order to produce an easily prototyped simulator. The printed simulator was layered with foam in order to replicate soft tissue structures. The models were instrumented with pedicle screws using standard operative technique and examined under fluoroscopy. Results Ten SpineBoxes were created using a single desktop 3D printer, with accurate replication of the cortico-cancellous interface using previously validated techniques. The models were able to be instrumented with pedicle screws successfully and demonstrated quality representation of bony structures under fluoroscopy. The total cost of model production was under $10. Conclusion The SpineBox represents the first open-access simulator for the instruction of spinal anatomy and pedicle screw placement. This study aims to provide institutions across the world with an economical and feasible means of spine surgical simulation for neurosurgical trainees and to encourage other rapid prototyping laboratories to investigate innovative means of creating educational surgical platforms in the modern era.


title: To Tweet or Not to Tweet—a Review of the Viral Power of Twitter for Infectious Diseases

text: PURPOSE OF REVIEW: With real-time communication crucial to both healthcare professionals (HCPs) and the public in infectious diseases (ID), social media networking sites has become even more important. Twitter is the most popular form of social media used for ID communication. We will review the power of Twitter in ID. RECENT FINDINGS: Twitter allows for real-time sharing of educational resources at ID scientific conferences, enabling individuals that are not able to attend conferences to follow conferences anytime anywhere and stimulate discussion around topics of interest with experts from across the globe. Further, Twitter chats are a valuable tool for stewardship, with different accounts periodically hosting chats on various stewardship topics. Several studies have also demonstrated the strong relationship between dissemination and citation impact of publications with the help of Twitter. There is great value in engaging with non-ID people on Twitter via dissemination of ID knowledge to other disciplines. Lastly, when used appropriately, Twitter is a useful site for distributing vaccine information, whether informally (by advocates and physicians) or formally (by government entities) and allows one to keep up with ongoing ID outbreaks in real time. SUMMARY: Twitter has transformed how we communicate in healthcare. Particularly in ID, where bacteria and viruses can enter/exit borders anytime anywhere, global real-time information about outbreaks and antimicrobial resistance for clinicians and the public is critical. Twitter has no hierarchy or barriers, is a conduit for global collaboration, and is a way for HCPs and the public to “social”ize on healthcare topics, if used appropriately.


title: Modelos predictivos de la epidemia de COVID-19 en España con curvas de Gompertz

text: RESUMEN Durante la crisis de salud internacional provocada por la pandemia de COVID-19, además de conocer los datos sobre contagios, muertes y ocupación de camas hospitalarias también es necesario hacer predicciones que ayuden a la gestión de la crisis por parte de las autoridades sanitarias. El presente trabajo tiene como objetivo describir la metodología utilizada para la elaboración de modelos predictivos de contagios y defunciones para la epidemia de COVID-19 en España basados en curvas de Gompertz. La metodología se aplica al total del país y a cada una de sus comunidades autónomas. De acuerdo con los datos oficiales publicados a la fecha de realización de este trabajo, y a través de los modelos descritos, estimamos un total de alrededor de 240.000 contagiados y 25.000 fallecidos al final de la epidemia. Pronosticamos el final de la epidemia entre los meses de junio y julio de 2020. ABSTRACT During the international health crisis caused by the COVID-19 pandemic, it is necessary not only to know the data on infections, deaths and the occupation of hospital beds, but also to make predictions that help health authorities in the management of the crisis. The present work aims to describe the methodology used to develop predictive models of infections and deaths for the COVID-19 epidemic in Spain, based on Gompertz curves. The methodology is applied to the country as a whole and to each of its Autonomous Communities. Based on the official data available on the date of this work, and through the models described, we estimate a total of around 240.000 infected and 25.000 deaths at the end of the epidemic. At a national level, we forecast the end of the epidemic between June and July 2020.


title: Homologue Scanning Mutagenesis Reveals Cd66 Receptor Residues Required for Neisserial Opa Protein Binding

text: The immunoglobulin-like family of CD66 antigens, present on human neutrophils and epithelial cells, are used as receptors for adhesins expressed by the pathogenic Neisseriae. N. gonorrhoeae strain MS11 can express 11 isoforms of these adhesins, called opacity-related (Opa) proteins. Each MS11 Opa protein recognizes a distinct spectrum of CD66 receptors. CD66–Opa binding is mediated by the NH(2)-terminal domain of the receptor and occurs through protein–protein interactions. In this report, we have investigated the molecular basis for the binding between the CD66 and Opa protein families by mapping amino acids in CD66 receptors that determine Opa protein binding. We performed homologue scanning mutagenesis between CD66e, which binds multiple Opa variants, and CD66b, which binds none, and tested both loss-of-function by CD66e and gain-of-function by CD66b in solution assays and in assays involving full-length receptors expressed by epithelial cells. We found that three residues in the CD66e N-domain are required for maximal Opa protein receptor activity. Opa proteins that recognize the same spectrum of native CD66 molecules showed differential binding of receptors with submaximal activity, indicating that the binding characteristics of these Opa proteins are actually slightly different. These data provide a first step toward resolving the structural requirements for Opa–CD66 interaction.


title: Identification and subcellular localization of porcine deltacoronavirus accessory protein NS6

text: Abstract Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Accessory proteins are genus-specific for coronavirus, and two putative accessory proteins, NS6 and NS7, are predicted to be encoded by PDCoV; however, this remains to be confirmed experimentally. Here, we identified the leader-body junction sites of NS6 subgenomic RNA (sgRNA) and found that the actual transcription regulatory sequence (TRS) utilized by NS6 is non-canonical and is located upstream of the predicted TRS. Using the purified NS6 from an Escherichia coli expression system, we obtained two anti-NS6 monoclonal antibodies that could detect the predicted NS6 in cells infected with PDCoV or transfected with NS6-expressing plasmids. Further studies revealed that NS6 is always localized in the cytoplasm of PDCoV-infected cells, mainly co-localizing with the endoplasmic reticulum (ER) and ER-Golgi intermediate compartments, as well as partially with the Golgi apparatus. Together, our results identify the NS6 sgRNA and demonstrate its expression in PDCoV-infected cells.


title: (Vi)-rushed into online group schema-therapy based day-treatment for older adults by the COVID-19 outbreak in the Netherlands

text: BACKGROUND –: Societal measures in context of the COVID-19 outbreak forced us to transform our schema therapy-based day-treatment for older adults with chronic affective disorders and personality problems into an online program. The objective of this paper is to present first impressions of this transformation. METHODS –: Using over-the-phone instructions initially, all patients were able to participate with the online therapy program. To reduce screen-time for patients, the non-verbal therapies were shortened. Four patients, aged 64-70 years, started our online program. RESULTS –: Therapists were positive about the online capabilities and resilience of patients to adapt to the new situation. Prejudices on limited effectiveness of online psychotherapy were counteracted. Sending homework by email and mail seems to facilitate therapy adherence. Non-verbal therapy could be important to stimulate the online group process. CONCLUSIONS –: We were positively surprised by the online capabilities of our geriatric mental health care patients and encourage further formal effectiveness studies.


title: Long noncoding RNA AVAN promotes antiviral innate immunity by interacting with TRIM25 and enhancing the transcription of FOXO3a

text: Accumulating evidence has shown that long noncoding RNAs (lncRNAs) are involved in several biological processes, including immune responses. However, the role of lncRNAs in antiviral innate immune responses remains largely unexplored. Here, we identify an uncharacterized human lncRNA from influenza A virus (IAV) patients, antivirus and activate neutrophil (AVAN), that is significantly up-regulated upon virus infection. Mechanistically, nuclear lncRNA-AVAN positively regulates the transcription of forkhead box O3A (FOXO3a) by associating with its promoter and inducing chromatin remodeling to promote neutrophil chemotaxis. Furthermore, we also found that cytoplasmic lncRNA-AVAN directly binds tripartite motif containing 25 (TRIM25) and enhances the association of TRIM25 and Retinoic acid inducible gene-1 proteins (RIG-I) and the ubiquitylation of RIG-I, thereby promoting TRIM25- and RIG-I-mediated antiviral innate immune signaling. More importantly, we enforced the expression of AVAN in transgenic mice and found that it significantly alleviated IAV virulence and virus production. Collectively, these findings highlight the potential clinical implications of lncRNA-AVAN as a key positive regulator of the antiviral innate immune response and a promising target for developing broad antiviral therapeutics.


Outlaw Nairobi versus The Pandemics


title: Defining lower airway bacterial infection in children with chronic endobronchial disorders

text: BACKGROUND: Differentiating lower airway bacterial infection from possible upper airway contamination in children with endobronchial disorders undergoing bronchoalveolar lavage (BAL) is important for guiding management. A diagnostic bacterial load threshold based on inflammatory markers has been determined to differentiate infection from upper airway contamination in infants with cystic fibrosis, but not for children with protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD), or bronchiectasis. METHODS: BAL samples from children undergoing bronchoscopy underwent quantitative bacterial culture, cytologic examination, and respiratory virus testing; a subset also had interleukin‐8 examined. Geometric means (GMs) of total cell counts (TCCs) and neutrophil counts were plotted by respiratory pathogen bacterial load. Logistic regression determined associations between age, sex, Indigenous status, antibiotic exposure, virus detection and bacterial load, and elevated TCCs (>400 × 10(3) cells/mL) and airway neutrophilia (neutrophils >15% BAL leukocytes). RESULTS: From 2007 to 2016, 655 children with PBB, CSLD, or bronchiectasis were enrolled. In univariate analyses, Indigenous status and bacterial load ≥10(5) colony‐forming units (CFU)/mL were positively associated with high TCCs. Viruses and bacterial load ≥10(4) CFU/mL were positively associated with neutrophilia; negative associations were seen for Indigenous status and macrolides. In children who had not received macrolide antibiotics, bacterial load was positively associated in multivariable analyses with high TCCs at ≥10(4) CFU/mL and with neutrophilia at ≥10(5) CFU/mL; GMs of TCCs and neutrophil counts were significantly elevated at 10(4) and 10(5) CFU/mL compared to negative cultures. CONCLUSIONS: Our findings support a BAL threshold ≥10(4) CFU/mL to define lower airway infection in children with chronic endobronchial disorders.


title: Treatment Considerations for COVID-19: A Critical Review of the Evidence (or Lack Thereof)

text: Abstract The novel severe acute respiratory syndrome coronavirus 2 is causing a worldwide pandemic that may lead to a highly morbid and potentially fatal coronavirus disease-19 (COVID-19). There is currently no drug that has been proven as an effective therapy for COVID-19. Several candidate drugs are being considered and evaluated for treatment. This includes clinically-available drugs, such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir, which are being repurposed for the treatment of COVID-19. Novel experimental therapies, such as remdesivir and favipiravir, are also actively being investigated for antiviral efficacy. Clinically-available and investigational immunomodulators, such as the IL-6 inhibitors tocilizumab and sarilumab and the anti-GMCSF lenzilumab, are being tested for their anticipated effect in counteracting the pro-inflammatory cytokine environment that characterizes severe and critical COVID-19. This review article examines the evidence behind the potential use of these leading drug candidates for the treatment of COVID-19. The authors conclude, based on this review, that there is still no high-quality evidence to support any of these proposed drug therapies. The authors, therefore, encourage the enrollment of eligible patients to multiple ongoing clinical trials that assess the efficacy and safety of these candidate therapies. Until the results of controlled trials are available, none of the suggested therapeutics is clinically proven as an effective therapy for COVID-19.


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title: Structural basis for the development of SARS 3CL protease inhibitors from a peptide mimic to an aza‐decaline scaffold

text: Design of inhibitors against severe acute respiratory syndrome (SARS) chymotrypsin‐like protease (3CL(pro)) is a potentially important approach to fight against SARS. We have developed several synthetic inhibitors by structure‐based drug design. In this report, we reveal two crystal structures of SARS 3CL(pro) complexed with two new inhibitors based on our previous work. These structures combined with six crystal structures complexed with a series of related ligands reported by us are collectively analyzed. To these eight complexes, the structural basis for inhibitor binding was analyzed by the COMBINE method, which is a chemometrical analysis optimized for the protein–ligand complex. The analysis revealed that the first two latent variables gave a cumulative contribution ratio of r(2) = 0.971. Interestingly, scores using the second latent variables for each complex were strongly correlated with root mean square deviations (RMSDs) of side‐chain heavy atoms of Met(49) from those of the intact crystal structure of SARS‐3CL(pro) (r = 0.77) enlarging the S(2) pocket. The substantial contribution of this side chain (∼10%) for the explanation of pIC(50)s was dependent on stereochemistry and the chemical structure of the ligand adapted to the S(2) pocket of the protease. Thus, starting from a substrate mimic inhibitor, a design for a central scaffold for a low molecular weight inhibitor was evaluated to develop a further potent inhibitor. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 391–403, 2016.


COVID-19 and Shock: A Cautionary Tale for Elderly Patients from a Pooled Analysis


title: Society of Robotic Surgery Review: Recommendations Regarding the Risk of COVID‐19 Transmission During Minimally Invasive Surgery

text: The COVID‐19 pandemic has created uncertainty regarding the safety and appropriate utilization of minimally invasive surgery (MIS) during this current outbreak. Surgical governing bodies such as Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) and the Royal Colleges of Surgery of Great Britain and Ireland have made statements regarding the possibility of COVID‐19 release into CO2 insufflant during MIS. The basis for this concern is prior evidence in the literature of other viral pathogen release during laparoscopic surgery. The recommendations are correctly based on caution given the lack of understanding of how COVID‐19 compares to other viruses with regard to transmission and presence in CO2 during MIS. In this review we have investigated the available literature on COVID‐19 transmission during MIS, address the implications of current and previously published recommendations and discuss steps to mitigate COVID‐19 transmission during MIS for staff and patient safety.


title: RETRACTED: Role of the SEL1L:LC3-I Complex as an ERAD Tuning Receptor in the Mammalian ER

text: This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors. The study reported that expression of misfolded proteins in the ER affects the composition of complexes containing EDEM1, SEL1L, and LC3-I, thereby modulating ERAD activity in the absence of UPR induction. During efforts to extend this work, we have been unable to replicate some of the results obtained by the first author of the paper. The authors have now found that Western blot data shown in Figures 1B, 3A, and 4A were inappropriately processed by the first author of the paper, such that they do not accurately report the original data. This could call into question some of our conclusions on how the presence of misfolded proteins might affect assembly and function of the ERAD machinery. The authors therefore wish to immediately retract the paper. The authors' lab continues working on the regulation of the ERAD machinery aiming to publish verified data in the near future. The authors sincerely apologize for any difficulties that may have been experienced by the scientific community. The first author, R.B., declined to sign the retraction notice.


title: Transmission dynamics: Data sharing in the COVID‐19 era

text: PROBLEM: The current coronavirus disease 2019 (COVID‐19) pandemic underscores the need for building and sustaining public health data infrastructure to support a rapid local, regional, national, and international response. Despite a historical context of public health crises, data sharing agreements and transactional standards do not uniformly exist between institutions which hamper a foundational infrastructure to meet data sharing and integration needs for the advancement of public health. APPROACH: There is a growing need to apply population health knowledge with technological solutions to data transfer, integration, and reasoning, to improve health in a broader learning health system ecosystem. To achieve this, data must be combined from healthcare provider organizations, public health departments, and other settings. Public health entities are in a unique position to consume these data, however, most do not yet have the infrastructure required to integrate data sources and apply computable knowledge to combat this pandemic. OUTCOMES: Herein, we describe lessons learned and a framework to address these needs, which focus on: (a) identifying and filling technology “gaps”; (b) pursuing collaborative design of data sharing requirements and transmission mechanisms; (c) facilitating cross‐domain discussions involving legal and research compliance; and (d) establishing or participating in multi‐institutional convening or coordinating activities. NEXT STEPS: While by no means a comprehensive evaluation of such issues, we envision that many of our experiences are universal. We hope those elucidated can serve as the catalyst for a robust community‐wide dialogue on what steps can and should be taken to ensure that our regional and national health care systems can truly learn, in a rapid manner, so as to respond to this and future emergent public health crises.


title: Effects of housing density on Long Evans and Fischer 344 rats

text: At many breeding facilities, rats are housed at relatively high densities until they are 5 weeks old, at which point they are either shipped for research or rehoused at standard cage densities according to weight. The authors carried out a pilot study in Long Evans and in Fischer 344 rats to investigate whether continuing to house rats at high densities (24 in(2) floor space per rat) past the age of 5 weeks, through puberty and into adulthood would alter behavioral or physiological parameters compared with raising rats at standard densities (about 72 in(2) floor space per rat). After rats reached puberty, the authors rehoused them with unfamiliar cagemates. The researchers evaluated clinical and behavioral signs of stress, weight, blood glucose concentration, white blood cell count and serum corticosterone concentration. Overall, cage density had little effect on the parameters measured, though gender seemed to affect stress in Long Evans rats. The results suggest that rats of these strains can be raised at the higher densities tested until any age and regrouped with unfamiliar cagemates without compromising rats' welfare or subsequent experimental data.


title: Anesthesia Considerations and Infection Precautions for Trauma and Acute Care Cases During the Coronavirus Disease 2019 Pandemic: Recommendations From a Task Force of the Chinese Society of Anesthesiology

text: Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. During the ongoing COVID-19 epidemic, most hospitals have postponed elective surgeries. However, some emergency surgeries, especially for trauma patients, are inevitable. For patients with suspected or confirmed COVID-19, a standard protocol addressing preoperative preparation, intraoperative management, and postoperative surveillance should be implemented to avoid nosocomial infection and ensure the safety of patients and the health care workforce. With reference to the guidelines and recommendations issued by the National Health Commission and Chinese Society of Anesthesiology, this article provides recommendations for anesthesia management of trauma and emergency surgery cases during the COVID-19 pandemic.


title: COVID-19 and Anosmia in Tehran, Iran

text: Patients with acute olfactory disorders typically present to the otolaryngologist with both acute hyposmia and less often with anosmia. With the onset of COVID-19 we have noticed an increase in the number of patients who have presented with new onset of complete smell loss to the senior author’s practice in Tehran, Iran. This anosmia and the frequency with which patients present is highly unusual. Coronaviruses have been known to cause common cold symptoms. COVID-19 infections have been described as causing more severe respiratory infections and the symptoms reported by authors from Wuhan, China have not specifically included anosmia. We describe patients who have presented during a two-week period of the COVID-19 pandemic with complete loss of sense of smell. Most had either no symptoms or mild respiratory symptoms. Many had a normal otolaryngologic exam. A relationship between COVID-19 and anosmia should be considered during the pandemic. We hypothesize that the mechanism of injury is similar to that of other coronavirus infections that cause central and peripheral neurologic deficits.


title: Infection risk in a gastroenterological ward during a nosocomial COVID‐19 infection event

text: The coronavirus disease (COVID‐19) first emerged in Wuhan, China, in December 2019 and rapidly infected a large number of individuals, and disease clusters have spread worldwide. A case of presumably nosocomial COVID‐19 was detected in the gastroenterological ward; however, appropriate precautions against contact and droplet prevented a subsequent infection cluster. This article is protected by copyright. All rights reserved.


title: Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence

text: Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-Δ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-Δ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-Δ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2α) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-Δ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2α dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-Δ7 and rTGEV-wt viruses showed that rTGEV-Δ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus.


title: The analysis of the relationships of Korean outbound tourism demand: Jeju Island and three international destinations

text: This paper investigates the determinants of the relationship among Korean outbound tourism demand for Jeju Island and three other Asian island countries using the multivariate generalized autoregressive conditional heteroskedasticity (MGARCH) and Vector Error Correction (VEC) models. It is found that pairwise conditional correlations among tourism demand for Jeju, Thailand, Singapore and the Philippines are not constant but time-varying. Estimated conditional correlations among Jeju and the three Asian countries are negative over some time periods. This implies that the three Asian countries are substitutes for Jeju in certain specific time horizons. The VEC model is used to investigate the short-run and long-run dynamic relationships and the results reveal that Industrial Production Index and real exchange rates had the positive or negative impact on conditional correlations of tourism demand for these destinations. Tourism policy implications are discussed for managing tourism demand for these destinations.


title: Astrocyte expression of a dominant‐negative interferon‐γ receptor

text: Interferon‐γ (IFN‐γ) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN‐γ signaling in astrocytes, transgenic mice (GFAP/IFN‐γR1ΔIC) expressing a dominant‐negative IFN‐γ receptor alpha chain under control of the astrocyte‐specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype. Transgene mRNA expression was detected only in the CNS, and the transgene‐encoded IFN‐γ receptor 1 colocalized with GFAP, which is consistent with astrocyte expression. Astrocytes from transgenic mice exhibited reduced IFN‐γ‐induced signaling as measured by major histocompatibility class II induction. Neither CNS inflammation nor perforin‐mediated clearance of a neurotropic mouse hepatitis virus from astrocytes was impaired following infection. Transgenic mice with impaired astrocyte responsiveness to IFN‐γ provide a model for studying the selective astrocyte‐dependent effects of this critical cytokine in CNS immunopathology. © 2005 Wiley‐Liss, Inc.


title: Creating a “Good Clinical Practices Inspection” Authentic Online Learning Environment through Educational Design Research

text: Educational design research (EDR) was applied to address the challenge of providing more public health professionals with opportunities to develop their knowledge and skills related to Good Clinical Practices (GCP) inspections. The conduct of clinical research in accordance with the principles of GCP is necessary to ensure that clinical research participants are not exposed to undue risk, and that data generated from the research are valid and accurate. The safety and efficacy of pharmaceuticals, medical devices, and other healthcare products depend upon the application of GCP. The World Health Organization has been providing a global face-to-face GCP Inspection course in Indonesia for a decade, but budget constraints only allow this course to be offered once a year to 15 participants. This paper describes how the move from a face-to-face course to an online authentic learning environment was accomplished through EDR and concludes with a discussion of design principles derived from the research. The results of a beta test of the new online course with 12 participants are also described in the paper.


title: A novel covid-19 mathematical model with fractional derivatives: Singular and nonsingular kernels

text: In this paper, we considered a new mathematical model depicting the possibility of spread within a given general population. The model is constructed with five classes including susceptible, exposed, infected, recovered and deaths. We presented a detailed analysis of the suggested model including, the derivation of equilibrium points endemic and disease-free, reproductive number using the next generation matrix, the stability analysis of the equilibrium points and finally the positiveness of the model solutions. The model was extended to the concept of fractional differentiation to capture different memories including power law, decay and crossover behaviors. A numerical method based on the Newton was used to provide numerical solutions for different memories.


title: The risk of SARS-CoV-2 transmission in the healthcare setting and potential impact of cohorting strategies

text: The threat of the COVID-19 pandemic of SARS-CoV-2 virus has grown since its start late last year. A customary response to a surge of a communicable disease is to separate healthcare systems into cohorts, such that patients with other conditions can be treated safely without risk of infection. A challenge with COVID-19 is the existence of currently asymptomatic infections, which without aggressive testing and isolation might enter the non-COVID-19 cohort either through unknowingly infected patients or health care workers. Using stochastic simulations we study the impacts of testing and personal protective equipment (PPE) use. In the base case without testing or PPE, healthcare is rapidly overwhelmed, and becomes a net contributor to the force of infection. We find that effective use of PPE by both HCW and patients can prevent this situation, while testing alone is less effective. We also find that even imperfectly effective use of PPE can provide substantial protection and decrease the force of infection. This illustrates the importance of maintaining supplies of PPE throughout healthcare systems


Mayo Clinic Strategies for COVID-19 Elements of an Effective Incident Command Center


title: SARS‐CoV‐2 asymptomatic and symptomatic patients and risk for transfusion transmission

text: Oral swabs, sputum, and blood samples from 18 asymptomatic and symptomatic patients with SARS‐CoV‐2 infection were examined using RT‐PCR testing in order to assess the risk of transfusion‐related transmission. In asymptomatic patients as well as patients with flu‐like symptoms and fever, no SARS‐CoV‐2 RNA could be detected in the blood or serum despite a clearly positive result in all throat swabs. As patients with symptoms of infectious disease will not be admitted to blood donation, the risk for transfusion transmission of SARS‐CoV‐2 seems to be negligible.


title: Impacto de la pandemia COVID-19 en la atención al paciente con cefalea en España: análisis de situación con una mirada al futuro

text: Resumen Introducción: La infección por SARS-CoV-2 ha tenido un enorme impacto en los sistemas sanitarios. España, donde la cefalea constituye el motivo principal de consulta ambulatoria en Neurología, es uno de los países con más casos notificados. Objetivo: Conocer el impacto de la pandemia COVID-19 en las Unidades de Cefaleas en España y evaluar cómo imaginan el futuro de estas estructuras los neurólogos responsables. Métodos: Estudio transversal mediante encuesta online distribuida a los responsables de las Unidades, realizada durante la sexta semana del Estado de Alarma. Resultados: La tasa de respuesta fue del 74%, con participación de centros de diferentes características y de todas las Comunidades Autónomas. El 95,8% describió limitaciones en la actividad presencial, un 60,4% mantuvo la consulta presencial preferente y el 45,8% los procedimientos urgentes. En el 91,7% de los centros la actividad presencial cancelada se sustituyó por consulta telefónica. El 95,8% de los encuestados afirmó que empleará material de protección personal en el futuro y el 86% pretende incorporar en mayor medida la telemedicina. La mayoría prevé un incremento en las listas de espera (93,8% en primeras visitas, 89,6% en revisiones y 89,4% en procedimientos) y una peor situación clínica de los pacientes, pero sólo un 15% cree que su estructura asistencial se verá debilitada. Conclusiones: Como consecuencia de la pandemia, la actividad asistencial e investigadora en cefaleas se ha reducido de manera notable. Esto pone de manifiesto la necesidad de un incremento de la oferta de telemedicina en nuestros centros en un futuro cercano. Abstract Introduction: The COVID-19 pandemic has had a great impact on healthcare systems. Spain, where headache is the main reason for outpatient neurology consultation, is one of the countries with the most reported cases of the disease. Objectives: This study aimed to analyse the impact of the COVID-19 pandemic on headache units in Spain and to evaluate how neurologists see the future of these units. Methods: We conducted a cross-sectional online survey of headache units during the sixth week of the state of alarm declared in Spain in response to the pandemic. Results: The response rate was 74%, with the participation of centres with different characteristics and from all Autonomous Communities of Spain. Limitations in face-to-face activity were reported by 95.8% of centres, with preferential face-to-face consultation being maintained in 60.4%, and urgent procedures in 45.8%. In 91.7% of centres, the cancelled face-to-face activity was replaced by telephone consultation. 95.8% of respondents stated that they would use personal protection equipment in the future, and 86% intended to increase the use of telemedicine. The majority foresaw an increase in waiting lists (93.8% for initial consultations, 89.6% for follow-up, and 89.4% for procedures) and a worse clinical situation for patients, but only 15% believed that their healthcare structures would be negatively affected in the future. Conclusions: As a consequence of the pandemic, headache care and research activity has reduced considerably. This demonstrates the need for an increase in the availability of telemedicine in our centres in the near future.


title: The changing face of pathogen discovery and surveillance

text: The pace of pathogen discovery is increasing dramatically. This reflects not only factors that enable the appearance and globalization of new microbial infections but also improvements in methods for ascertainment. New molecular diagnostic platforms; investments in pathogen surveillance in wildlife, domestic animals and humans; and the advent of social media tools that mine the world wide web for clues to outbreaks of infectious disease are proving invaluable in early recognition of threats to public health. Additionally, models of microbial pathogenesis are becoming more complex, providing insights into the mechanisms by which microorganisms can contribute to chronic illnesses like cancer, peptic ulcer disease and mental illness. Here we review the contributions of each of these elements to infectious disease emergence and strategies for addressing the challenges of pathogen surveillance and discovery.


title: Zur antimikrobiellen und viruziden Wirksamkeit von Octenidin-Lutschtabletten

text: Zusammenfassung Die Verwendung von Octenidin in der Darreichungsform als Lutschtablette wurde erst 2004 patentiert. Das antivirale, viruzide und vor allem antimikrobielle Wirkungsspektrum der Substanz ist vergleichsweise breit und für die Substanz in Monopräparaten noch wenig untersucht. Die bislang vorliegenden Daten unterstreichen jedoch die vielfältigen Möglichkeiten der prophylaktischen und therapeutischen Anwendung der Substanz und legen die Applikation als flankierende Maßnahme z. B. bei der Dekolonisation Antibiotika-resistenter (MRSA) Carrier nahe.


title: Establishment of CDC Global Rapid Response Team to Ensure Global Health Security

text: The 2014–2016 Ebola virus disease epidemic in West Africa highlighted challenges faced by the global response to a large public health emergency. Consequently, the US Centers for Disease Control and Prevention established the Global Rapid Response Team (GRRT) to strengthen emergency response capacity to global health threats, thereby ensuring global health security. Dedicated GRRT staff can be rapidly mobilized for extended missions, improving partner coordination and the continuity of response operations. A large, agencywide roster of surge staff enables rapid mobilization of qualified responders with wide-ranging experience and expertise. Team members are offered emergency response training, technical training, foreign language training, and responder readiness support. Recent response missions illustrate the breadth of support the team provides. GRRT serves as a model for other countries and is committed to strengthening emergency response capacity to respond to outbreaks and emergencies worldwide, thereby enhancing global health security.


title: Inactivation of West Nile virus, vaccinia virus and viral surrogates for relevant and emergent viral pathogens in plasma‐derived products

text: Background and Objectives Human plasma is the source of a wide variety of therapeutic proteins, yet it is also a potential source of viral contamination. Recent outbreaks of emergent viral pathogens, such as West Nile virus, and the use of live vaccinia virus as a vaccine have prompted a reassessment of the viral safety of plasma‐derived products. The purpose of this study was to evaluate the efficacy of current viral inactivation methods for West Nile and vaccinia viruses and to reassess the use of model viruses to predict inactivation of similar viral pathogens. Materials and Methods Virus‐spiked product intermediates were processed using a downscaled representation of various manufacturing procedures. Virus infectivity was measured before and after processing to determine virus inactivation. Results The results demonstrated effective inactivation of West Nile virus, vaccinia virus and a model virus, bovine viral diarrhoea virus, during pasteurization, solvent/detergent treatment and caprylate treatment. Caprylate provided rapid and effective inactivation of West Nile virus, vaccinia virus, duck hepatitis B virus and Sindbis virus. Inactivation of West Nile virus was similar to that of bovine viral diarrhoea virus. Conclusions This study demonstrates that procedures used to inactivate enveloped viruses in manufacturing processes can achieve inactivation of West Nile virus and vaccinia virus. In addition, the data support the use of model viruses to predict the inactivation of similar emergent viral pathogens.


title: First-in-human clinical trials with vaccines—what regulators want

text: Several factors should be taken into account when it comes to the first exposure of humans to a novel vaccine.


title: Differences in race and other state‐level characteristics and associations with mortality from COVID‐19 infection

text: As reporting of COVID‐19 at the US state level has become more granular, many states have reported a higher proportion of deaths among African‐Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital‐beds/ventilators per‐capita), median household income and high‐school graduation rates. We report a higher death rate among states with a greater proportion of African‐American residents despite adjusting for case rates and state‐level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID‐19. This article is protected by copyright. All rights reserved.


title: Detection of Ascitic Feline Coronavirus RNA from Cats with Clinically Suspected Feline Infectious Peritonitis

text: Ascitic feline coronavirus (FCoV) RNA was examined in 854 cats with suspected feline infectious peritonitis (FIP) by RT-PCR. The positivity was significantly higher in purebreds (62.2%) than in crossbreds (34.8%) (P<0.0001). Among purebreds, the positivities in the Norwegian forest cat (92.3%) and Scottish fold (77.6%) were significantly higher than the average of purebreds (P=0.0274 and 0.0251, respectively). The positivity was significantly higher in males (51.5%) than in females (35.7%) (P<0.0001), whereas no gender difference has generally been noted in FCoV antibody prevalence, indicating that FIP more frequently develops in males among FCoV-infected cats. Genotyping was performed for 377 gene-positive specimens. Type I (83.3%) was far more predominantly detected than type II (10.6%) (P<0.0001), similar to previous serological and genetic surveys.


The PEGASUS Conferences: A unique avenue to bridge evidence and action


title: Use of a multiplex PCR/RT‐PCR approach to assess the viral causes of influenza‐like illnesses in Cambodia during three consecutive dry seasons

text: Acute respiratory infections are a major cause of mortality and morbidity worldwide. Using multiplex PCR/RT‐PCR methods for the detection of 18 respiratory viruses, the circulation of those viruses during 3 consecutive dry seasons in Cambodia was described. Among 234 patients who presented with influenza‐like illness, 35.5% were positive for at least one virus. Rhinoviruses (43.4%), parainfluenza (31.3%) viruses and coronaviruses (21.7%) were the most frequently detected viruses. Influenza A virus, parainfluenza virus 4 and SARS‐coronavirus were not detected during the study period. Ninety apparently healthy individuals were included as controls and 10% of these samples tested positive for one or more respiratory viruses. No significant differences were observed in frequency and in virus copy numbers for rhinovirus detection between symptomatic and asymptomatic groups. This study raises questions about the significance of the detection of some respiratory viruses, especially using highly sensitive methods, given their presence in apparently healthy individuals. The link between the presence of the virus and the origin of the illness is therefore unclear. J. Med. Virol. 82:1762–1772, 2010. © 2010 Wiley‐Liss, Inc.


title: IFITMs restrict the replication of multiple pathogenic viruses

text: The IFITM family of proteins inhibit a growing number of pathogenic viruses, among them influenza A virus, dengue virus, hepatitis C virus, and Ebola virus. This review covers recent developments in our understanding of the IFITM’s molecular determinants, potential mechanisms of action, and impact on pathogenesis.


title: A distinctive skin rash associated with Coronavirus Disease 2019 ?

text: A skin rash has been reported in 2 out of 1.099 patients presenting with Coronavirus disease 2019 in China [1], as in 14 of 48 patients with the same disease in Italia, but unfortunately without further description of its semiology [2]. We wish to report here the case of a woman who presented, coincidently with Covid‐19, a skin rash that had an original picture.


title: Intranasal delivery of adjuvant-free peptide nanofibers elicits resident CD8+ T cell responses

text: Abstract Influenza vaccines that can be administered intranasally or by other needle-free delivery routes have potential advantages over injected formulations in terms of patient compliance, cost, and ease of global distribution. Supramolecular peptide nanofibers have been investigated previously as platforms for vaccines and immunotherapies and have been shown to raise immune responses in the absence of exogenous adjuvants and without measurable inflammation. However, at present it has not been tested whether the immunogenicity of these materials extends to the intranasal route. Here we investigated the extent to which self-assembled peptide nanofibers bearing an influenza peptide epitope elicit antigen-specific CD8+ T cell responses when delivered intranasally, and we compared these responses with those elicited by subcutaneous immunization. Peptides containing an epitope from influenza acid polymerase (PA) and the Q11 self-assembly domain formed nanofibers that were avidly taken up by dendritic cells in lung-draining mediastinal lymph nodes after intranasal immunization. Intranasally delivered nanofibers generated greater antigen-specific CD8+ T cell responses in the lung-draining lymph nodes than subcutaneous immunizations while retaining the non-inflammatory character of the materials observed in other delivery sites. The CD8+ T cells elicited systemically were functional as assessed by their ability to produce IFN-γ ex vivo, lyse epitope-pulsed target cells in vivo, and diminish viral loads in infected mice. Compared to subcutaneously delivered nanofibers, intranasally delivered peptide nanofibers significantly increased the number of persisting antigen-specific tissue resident memory CD8+ T cells in the lung, allowing for a more rapid response to infection at 6 weeks post-vaccination. These results indicate that intranasally delivered self-assembled peptide nanofibers are immunogenic when delivering CD8+ epitopes without adjuvant or CD4+ epitopes, are non-inflammatory, and promote more lung-resident memory CD8+ T cells compared to subcutaneous immunization.


title: The impact of COVID-19 pandemic on urological emergencies: a single-center experience

text: PURPOSE: COVID-19 pandemic represents a novel challenge for healthcare systems, and it affects even the daily urological practice. Italy was the first country after China to experience a lock-down period. Our objective is to determine whether, during the COVID-19 period, there has been any modification in urological emergencies. METHODS: we retrospectively reviewed urgent urological consultations requested by the Emergency Department (ED) of Padua University Hospital in the 36-day period between February 22nd and March 30th, 2020 and compared them to the prior year cases within a similar time frame (February 24th to March 31st, 2019). Pediatric population (age < 15 years); surgical complications and traumas were excluded to avoid confounding from the reduction of activities during the lockdown. The number of daily consultations, the number of invasive procedures performed and admissions were evaluated, together with the predictors of admission were identified through multivariate logistic regression models. RESULTS: The final sample resulted in 107 consultations performed in 2020 and 266 in 2019. A higher number of daily consultations was performed during 2019 (7.33 vs 2.97, p < 0.001). Similarly, the number of daily-invasive procedures was higher in 2019 (p = 0.006), while there was no difference in the number of daily admissions (15 vs 12, p = 0.80). On multivariate analysis, the year (2020 vs 2019, OR 2.714, 95% CI 1.096–6.757, p = 0.0297) was a significant predictor of admission. CONCLUSIONS: Urgent urology practice was affected during COVID-19 pandemic with a remarkable reduction in urgent urological consultations; furthermore, a higher risk of admissions was observed in 2020. The consequences of a potentially delayed diagnosis remain to be determined. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00345-020-03264-2) contains supplementary material, which is available to authorized users.


title: Ambient temperature, birth rate, and birth outcomes: evidence from South Korea

text: The effects from rising temperatures, a symptom of climate change, have become a significant concern. This study finds that one additional day with a maximum temperature of 30–32 °C (86–89.6 °F), relative to a day with a temperature of 28–30 °C (82.4–86 °F), decreases the birth rate 9 months later by 0.24%, or 92 babies per month in South Korea. This result is robust to various specifications and samples. This study also found that the impact of the temperature bin did not vary according to the mother’s characteristics, including education and age. That is, high temperature has no differential effect on mothers of different backgrounds. Finally, we found no significant temperature effect on birth outcomes, but we cannot rule out that children born 9 months after summer heat are a selected (healthy) group.


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title: Patient-Centric Care for Parkinson's Disease: From Hospital to the Community

text: Parkinson's disease (PD) is a chronic neurodegenerative disease with complex motor and non-motor symptoms often leading to significant caregiver burden. An integrated, multidisciplinary care setup involving different healthcare professionals is the mainstay in the holistic management of PD. Many challenges in delivering multidisciplinary team (MDT) care exist, such as insufficient expertise among different healthcare professionals, poor interdisciplinary collaboration, and communication. The need to attend different clinics, incurring additional traveling and waiting time for allied health therapies can also make MDT care more burdensome. By shifting MDT care to local community settings and into patients' homes, patient-centered care can be achieved. In Singapore, the National Neuroscience Institute created the Community Care Partners Programme in 2007 to bring the allied MDT team to the community and nurse-led Integrated Community Care Programme for Parkinson's Disease in 2012 to provide care in community and at patient's home. However, attaining MDT care in the community setting is difficult to achieve where there is a shortage of PD-trained professionals. As such, interdisciplinary and transdisciplinary management would be other best practice options to deliver patient-centric care in PD. Telemedicine could be another viable option to bring the MDT closer to the patient.


title: A Delphi-based approach to developing expert systems with the cooperation of multiple experts

text: Abstract Knowledge acquisition has been a critical bottleneck in building knowledge-based systems. In past decades, several methods and systems have been proposed to cope with this problem. Most of these methods and systems were proposed to deal with the acquisition of domain knowledge from single expert. However, as multiple experts may have different experiences and knowledge on the same application domain, it is necessary to elicit and integrate knowledge from multiple experts in building an effective expert system. Moreover, the recent literature has depicted that “time” is an important parameter that might significantly affect the accuracy of inference results of an expert system; therefore, while discussing the elicitation of domain expertise from multiple experts, it becomes an challenging and important issue to take the “time” factor into consideration. To cope with these problems, in this study, we propose a Delphi-based approach to eliciting knowledge from multiple experts. An application on the diagnosis of Severe Acute Respiratory Syndrome has depicted the superiority of the novel approach.


title: Digestive system is a potential route of COVID-19: an analysis of single-cell coexpression pattern of key proteins in viral entry process

text: OBJECTIVE: Since December 2019, a newly identified coronavirus (severe acute respiratory syndrome coronavirus (SARS-CoV-2)) has caused outbreaks of pneumonia in Wuhan, China. SARS-CoV-2 enters host cells via cell receptor ACE II (ACE2) and the transmembrane serine protease 2 (TMPRSS2). In order to identify possible prime target cells of SARS-CoV-2 by comprehensive dissection of ACE2 and TMPRSS2 coexpression pattern in different cell types, five datasets with single-cell transcriptomes of lung, oesophagus, gastric mucosa, ileum and colon were analysed. DESIGN: Five datasets were searched, separately integrated and analysed. Violin plot was used to show the distribution of differentially expressed genes for different clusters. The ACE2-expressing and TMPRRSS2-expressing cells were highlighted and dissected to characterise the composition and proportion. RESULTS: Cell types in each dataset were identified by known markers. ACE2 and TMPRSS2 were not only coexpressed in lung AT2 cells and oesophageal upper epithelial and gland cells but also highly expressed in absorptive enterocytes from the ileum and colon. Additionally, among all the coexpressing cells in the normal digestive system and lung, the expression of ACE2 was relatively highly expressed in the ileum and colon. CONCLUSION: This study provides the evidence of the potential route of SARS-CoV-2 in the digestive system along with the respiratory tract based on single-cell transcriptomic analysis. This finding may have a significant impact on health policy setting regarding the prevention of SARS-CoV-2 infection. Our study also demonstrates a novel method to identify the prime cell types of a virus by the coexpression pattern analysis of single-cell sequencing data.


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title: Improving influenza vaccine virus selectionReport of a WHO informal consultation held at WHO headquarters, Geneva, Switzerland, 14–16 June 2010

text: • For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. • The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy‐making community of the complexity of influenza vaccine virus selection. • The selection process is highly coordinated and involves continual year‐round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). • Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non‐antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. • Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. • Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. • Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays – for example based upon advanced recombinant DNA and protein technologies – may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. • Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large‐scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. • Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well‐characterized banks of age‐stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. • Advances in high‐throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X‐ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. • Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non‐mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. • The adoption of alternative vaccine technologies – such as live‐attenuated, quadrivalent or non‐HA‐based vaccines – has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high‐growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. • The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations.


title: Comparison of alternative models of human movement and the spread of disease

text: Predictive models for the spatial spread of infectious diseases has received much attention in recent years as tools for the management of infectious diseas outbreaks. Prominently, various versions of the so-called gravity model, borrowed from transportation theory, have been used. However, the original literature suggests that the model has some potential misspecifications inasmuch as it fails to capture higher-order interactions among population centers. The fields of economics, geography and network sciences holds alternative formulations for the spatial coupling within and among conurbations. These includes Stouffer’s rank model, Fotheringham’s competing destinations model and the radiation model of Simini et al. Since the spread of infectious disease reflects mobility through the filter of age-specific susceptibility and infectivity and since, moreover, disease may alter spatial behavior, it is essential to confront with epidemiological data on spread. To study their relative merit we, accordingly, fit variants of these models to the uniquely detailed dataset of prevaccination measles in the 954 cities and towns of England and Wales over the years 1944-65 and compare them using a consistent likelihood framework. We find that while the gravity model is a reasonable first approximation, both Stouffer’s rank model, an extended version of the radiation model and the Fotheringham competing destinations model provide significantly better fits, Stouffer’s model being the best. Through a new method of spatially disaggregated likelihoods we identify areas of relatively poorer fit, and show that it is indeed in densely-populated conurbations that higher order spatial interactions are most important. Our main conclusion is that it is premature to narrow in on a single class of models for predicting spatial spread of infectious disease. The supplemental materials contain all code for reproducing the results and applying the methods to other data sets. The ability to predict how infectious disease will spread is of great importance in the face of the numerous emergent and re-emergent pathogens that currently threatening human well-being. We identified a variety of alternative models that predict human mobility as as a function of population distribution across a landscape. These consider some models that account for pair-wise interactions between population centers, as well as some that allow for higher-order interactions. We trained the models using a uniquely rich spatiotemporal data set on pre-vaccination measles in England and wales (1944-65), which comprises more than a million records from 954 cities and towns. Likelihood rankings of the different models reveal strong evidence for higher-order interactions in the form of competition among cities as destinations for travelers and, thus, dilution of spatial transmission. The currently most commonly used so-called ‘gravity’ models were far from the best in capturing spatial disease dynamics.


title: Current issue in tourism: The evolution of travel medicine research: A new research agenda for tourism?

text: There has been considerable growth in interest in the field of travel medicine and the intersection with Tourism Studies since the 1990s. Yet this interest from a medical perspective is not new as a review of The Lancet, one of the most well-established medical journals, shows. What is new is the way in which the interest in travel medicine has developed across the science–social science divide and has now become one strand of a wider practitioner and academic interest in tourist well-being. With the exception of studies on technology and tourism and environmental science and tourism (e.g. climate change), this science–social science intersection has been comparatively absent from research in Tourism Studies. For this reason, this current issue's paper seeks to broadly outline the evolution of this area of study and some of the influential studies published to date along with some of the research agendas now emerging in this new area of study.


title: Evaluation of Patients under Investigation for MERS-CoV Infection, United States, January 2013–October 2014

text: Middle East respiratory syndrome (MERS) cases continue to be reported from the Middle East. Evaluation and testing of patients under investigation (PUIs) for MERS are recommended. In 2013–2014, two imported cases were detected among 490 US PUIs. Continued awareness is needed for early case detection and implementation of infection control measures.


title: Potential role of incretins in diabetes and COVID-19 infection: a hypothesis worth exploring

text: Patients with diabetes mellitus have been reported to be at a high risk of complications from SARS-CoV2 virus infection (COVID-19). In type 2 diabetes, there is a change in immune system cells, which shift from an anti-inflammatory to a predominantly pro-inflammatory pattern. This altered immune profile may induce important clinical consequences, including increased susceptibility to lung infections; and enhanced local inflammatory response. Furthermore, dipeptidyl peptidase 4 (DPP4) enzyme is highly expressed in the lung, and that it may have additional actions besides its effects on glucose metabolism, which might exert profound pro-inflammatory effects. We briefly review the impact on the inflammatory system of DPP4 for its possible detrimental effect on COVID-19 syndrome, and of DPP4 inhibitors (gliptins), currently used as glucose lowering agents, which may have the potential to exert positive pleiotropic effect on inflammatory diseases, in addition to their effects on glucose metabolism. Thanks to these ancillary effects, gliptins could potentially be “repurposed” as salutary drugs against COVID-19 syndrome, even in non-diabetic subjects. Clinical studies should be designed to investigate this possibility.


title: Prospects for Emerging Infections in East and Southeast Asia 10 Years after Severe Acute Respiratory Syndrome

text: It is 10 years since severe acute respiratory syndrome (SARS) emerged, and East and Southeast Asia retain a reputation as a hot spot of emerging infectious diseases. The region is certainly a hot spot of socioeconomic and environmental change, and although some changes (e.g., urbanization and agricultural intensification) may reduce the probability of emerging infectious diseases, the effect of any individual emergence event may be increased by the greater concentration and connectivity of livestock, persons, and products. The region is now better able to detect and respond to emerging infectious diseases than it was a decade ago, but the tools and methods to produce sufficiently refined assessments of the risks of disease emergence are still lacking. Given the continued scale and pace of change in East and Southeast Asia, it is vital that capabilities for predicting, identifying, and controlling biologic threats do not stagnate as the memory of SARS fades.