title: Travel-related infections in mainland China, 2014–16: an active surveillance study

text: Summary Background Transmission of infection through international travel is a growing health issue, and the frequency of imported infection is increasing in China. We aimed to quantify the total number of infections imported into mainland China by arriving travellers. Methods We actively surveyed arriving travellers at all 272 international entry–exit ports in mainland China. Suspected cases were detected through fever screening, medical inspection, self-declaration, and reporting by on-board staff. Participants completed a standardised questionnaire with questions about demographics, their travel itinerary (including detailed information about all countries or regions visited), and clinical manifestations. Nasopharyngeal swabs, sputum samples, faecal samples, vomitus, blood, and serum were collected as appropriate for diagnoses. Diagnosis was made by specific laboratory tests according to the national technical guidelines. Infections were classified as respiratory, gastrointestinal, vector-borne, blood-transmitted and sex-transmitted, or mucocutaneous. We divided arriving travellers into two groups: travellers coming from countries other than China, and travellers coming from Hong Kong, Macau, and Taiwan. We integrated surveillance data for 2014–16, calculated incidences of travel-related infections, and compared the frequency of infections among subgroups. Findings Between Jan 1, 2014, and Dec 31, 2016, 22 797 cases were identified among 805 993 392 arriving travellers—an overall incidence of 28·3 per million. 45 pathogens were detected in participants: 18 respiratory (19 662 cases), ten gastrointestinal (189 cases), seven vector-borne (831 cases), seven blood-transmitted and sex-transmitted (1531 cases), and three mucocutaneous (584 cases). Both the overall number and incidence of infection were more than five times higher in 2016 than in 2014. Case numbers and incidences also varied substantially by province, autonomous region, and municipality. Overall, 17 643 (77%) infections were detected by fever screening, but 753 (49%) blood-transmitted and sex-transmitted infections were identified through medical inspection. 14 305 (73%) cases of respiratory infection and 96 (51%) of gastrointestinal infections were in tourists. Tuberculosis, hepatitis A virus, vector-borne, and blood-transmitted and sex-transmitted infections were common among Chinese labourers who worked abroad. Dengue and malaria were most commonly diagnosed in travellers arriving from Africa. 12 126 (93%) of the 12 985 cases arriving from Hong Kong, Macau, or Taiwan were respiratory infections. Hand, foot, and mouth disease accounted for 2·90% of infections in travellers from Hong Kong, Macau, or Taiwan and 0·31% of infections in international travellers. Interpretation This report is the first to characterise the profile of travel-related infections among arriving travellers in mainland China. Our findings should increase public awareness of the potential risk of imported infections, and help health-care providers to make evidence-based health recommendations to travellers. Funding The Natural Science Foundation of China.


Influenza vaccination coverage in Japan


title: Economic evaluation of participation in a voluntary Johne's disease prevention and control program from a farmer's perspective–The Alberta Johne's Disease Initiative

text: Abstract The Alberta Johne's Disease Initiative (AJDI) is a Johne's disease (JD) control program with the goal of reducing the spread of Mycobacterium avium ssp. paratuberculosis (MAP) through implementation of best management practices. The objective was to estimate the economic benefit of participation in the AJDI. A decision tree was constructed in which disease prevalence, test characteristics, and probabilities for implementation of best management practices suggested by herd veterinarians were implemented. Analysis was performed using a Markov analysis, and input data were assigned using estimates from the AJDI and published data. A cost-effectiveness analysis was performed and the net benefit of participation (from the perspective of a dairy farmer) in the AJDI compared with no participation was calculated. A series of 1-way sensitivity analyses were used to control for uncertainty. Farms participating in the AJDI were estimated to have a net benefit of Can$74 per cow over the course of 10yr. If project costs were covered by the participating farm, the net benefit was Can$27. In addition to the effects on MAP infection, a reduction in calf diarrhea was modeled for farms that improved their calf management through the use of pasteurizers. In that case, the additional costs outweighed additional revenues compared with the baseline analysis, resulting in a reduced net benefit of Can$19. Participation would not be cost effective if cows in early stages of MAP infection did not have decreased production and if prevalence of MAP infection did not increase on farms with poor management. A limitation of the study, despite high uncertainty in some input parameters, was the lack of knowledge regarding changes in prevalence on farms with various management strategies. In conclusion, participation in the AJDI was cost effective for the average Alberta dairy farm.


title: Genotyping and macrolide resistance of Mycoplasma pneumoniae identified in children with community-acquired pneumonia in Medellín, Colombia

text: Abstract Objectives The aim of this study was to describe the genotypes and the main characteristics of community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae in hospitalized children in Medellín and neighboring municipalities during the period 2011–2012. Methods The M. pneumoniae genotype was determined by PCR and sequencing of the p1 and 23S rRNA genes from induced sputum samples and nasopharyngeal swabs (NPS). Samples were obtained from children with CAP who were hospitalized in 13 healthcare centers. In addition, a spatio-temporal analysis was performed to identify the potential risk areas and clustering of the cases over time. Results A variant of type 2 was the dominant genotype in the induced sputum (96.1%) and NPS (89.3%) samples; the type 1 variant was identified in 3.9% and 10.7% of these samples, respectively. No strains with mutations in the 23S rRNA gene associated with macrolide resistance were found. The cases in Medellín were mainly concentrated in the northeastern areas and western districts. However, no temporal relationship was found among these cases. Conclusions A variant of type 2 of M. pneumoniae prevailed among children with CAP during the study period. No strains with mutations associated with macrolide resistance were found.


Adalimumab for Treatment of Hidradenitis Suppurativa During the COVID-19 Pandemic: Safety Considerations


title: The United States and global health: inseparable and synergistic? The Institute of Medicine's report on global health

text: In the wake of dynamic economic and political transitions worldwide, the Institute of Medicine recently released its report advocating investments in global health from the United States (US). The expert panel reinforces the ‘transnational and interdisciplinary’ nature of global health research and practice as an endeavor ‘to improve health and achieve greater equity for all people worldwide.’ This report was judiciously timed given the growing recognition of global health, and is also acknowledged for incorporating themes that are particularly pertinent to the twenty-first century. New paradigms are introduced, denouncing the dichotomous distinction between rich and poor countries with the rapidly transitioning countries emerging as global powers, and affirming the need for models of respectful partnership and wider translation of science into practice. Cultivating sustainable partnerships and investing in the understanding and combat of diseases worldwide will become increasingly important for the US to maintain its global competitiveness, and may offer lessons in innovation, efficiency, and organization of institutions and human resources.


title: Single-domain antibodies as promising experimental tools in imaging and isolation of porcine epidemic diarrhea virus

text: Single-domain antibody (sdAb) or nanobody possesses specific features non-accessible for conventional antibodies that make them suitable for research and biotechnological applications. Porcine epidemic diarrhea virus (PEDV) causes lethal diarrhea in piglets, resulting in great economic losses all over the world. To detect and isolate PEDV rapidly and accurately is important for the control and further research of the clinical PEDV strains. In this study, four sdAb fragments (sdAb-Mc19/29/30/37) targeting the membrane (M) protein of PEDV were selected from sdAb library that was constructed through M protein-immunized Camelus bactrianus. The selected sdAb-Mcs were solubly expressed in Escherichia coli. The functional characteristics analysis revealed that the recombinant sdAb-Mcs have excellent binding activity and specificity to M protein but have no neutralizing activity to PEDV. For further application, sdAb-Mc37 was conjugated with quantum dots to synthesize a nanoprobe for imaging PEDV in vero cells. The observed fluorescence in vero cells clearly reflects that PEDV virions can be reliably recognized and labeled by the nanoprobe. Furthermore, the sdAb-Mc29 was conjugated with superparamagnetic nanobeads to construct immunomagnetic nanobeads (IMNBs) used to isolate PEDV. One PEDV strain was successfully isolated from clinical fecal sample, suggesting IMNBs as a novel and efficient tool suitable for PEDV isolation from clinical samples. This study provided a novel application and substantiated the suitability of sdAb as a specific binder for the isolation of viruses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-018-9324-7) contains supplementary material, which is available to authorized users.


title: The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis

text: Abstract Apoptosis, necroptosis and pyroptosis represent three distinct types of regulated cell death forms, which play significant roles in response to viral and bacterial infections. Whereas apoptosis is characterized by cell shrinkage, nuclear condensation, bleb formation and retained membrane integrity, necroptosis and pyroptosis exhibit osmotic imbalance driven cytoplasmic swelling and early membrane damage. These three cell death forms exert distinct immune stimulatory potential. The caspase driven apoptotic cell demise is considered in many circumstances as anti-inflammatory, whereas the two lytic cell death modalities can efficiently trigger immune response by releasing damage associated molecular patterns to the extracellular space. The relevance of these cell death modalities in infections can be best demonstrated by the presence of viral proteins that directly interfere with cell death pathways. Conversely, some pathogens hijack the cell death signaling routes to initiate a targeted attack against the immune cells of the host, and extracellular bacteria can benefit from the destruction of intact extracellular barriers upon cell death induction. The complexity and the crosstalk between these cell death modalities reflect a continuous evolutionary race between pathogens and host. This chapter discusses the current advances in the research of cell death signaling with regard to viral and bacterial infections and describes the network of the cell death initiating molecular mechanisms that selectively recognize pathogen associated molecular patterns.


title: Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules

text: Abstract Hypertension is a diverse illness interlinked with cerebral, cardiovascular (CVS) and renal abnormalities. Presently, the malady is being treated by focusing on Renin- angiotensin system (RAS), voltage-gated calcium channels, peripheral vasodilators, renal and sympathetic nervous systems. Cardiovascular and renal abnormalities are associated with the overactivation of RAS, which can be constrained by angiotensin- converting enzyme inhibitors (ACEIs), angiotensin II (Ang-II) -AT1 receptor blockers (ARBs) and renin inhibitors. The latter is a new player in the old system. The renin catalyzes the conversion of angiotensinogen to Angiotensin I (Ang-I). This can be overcome by inhibiting renin, a preliminary step, eventually hinders the occurrence of the cascade of events in the RAS. Various peptidomimetics, the first-generation renin inhibitors developed six decades ago have limited drug-like properties as they suffered from poor intestinal absorption, high liver first-pass metabolism and low oral bioavailability. The development of chemically diverse molecules from peptides to nonpeptides expanded the horizon to achieving direct renin inhibition. Aliskiren, a blockbuster drug that emerged as a clinical candidate and got approved by the US FDA in 2007 was developed by molecular modeling studies. Aliskiren indicated superior to average efficacy and with minor adverse effects relative to other RAS inhibitors. However, its therapeutic use is limited by poor oral bioavailability of less than 2% that is similar to first-generation peptidic compounds. In this review, we present the development of direct renin inhibitors (DRIs) from peptidic to nonpeptidics that lead to the birth of aliskiren, its place in the treatment of cardiovascular diseases and its limitations.


title: Altered eosinophil levels as a result of viral infection in asthma exacerbation in childhood

text: Respiratory viral infection is known to be a significant cause of asthma exacerbation. Eosinophils have been considered to play an important role in the pathogenesis of virus‐induced asthma exacerbations. To determine how often asthma exacerbation is caused by virus infections and to examine the relationship between eosinophilia and asthma episode, we investigated 64 children who experienced asthma attacks between October 1999 and March 2000. We used rapid enzyme immunoassays to detect antigens of respiratory syncytial virus (RSV), influenza A virus, and adenovirus in nasopharyngeal secretions (NPS) of these children, and enumerated eosinophils in the blood and NPS. We detected RSV in 27% and influenza A virus in 17% of the patients. No adenovirus infection or RSV/influenza A co‐infection was detected. RSV‐infected children were younger (3.85 ± 0.83 years old) than influenza A virus‐infected patients (5.23 ± 1.34 years old). Eighty‐two per cent of patients in the RSV group and 36% of patients in the influenza A virus group had moderate‐to‐severe asthma episodes (p < 0.05). In RSV‐infected children, the eosinophil counts in NPS were higher in the ‘severe’ group, and younger patients had a greater number of eosinophils in their NPS than older patients (p < 0.05). These trends were not found in influenza A virus patients. In conclusion, our results indicate that, compared with influenza A virus‐induced asthma attacks, RSV infection had a higher probability of being associated with asthma exacerbation in infants and younger children and induced attacks of greater severity. The increase in the number of eosinophils in the NPS of RSV‐infected children may be responsible, in part, for these differences.


title: Estimación del efecto en el tamaño y la supervivencia de los tumores cutáneos debido al confinamiento por COVID-19: Modelo basado en un crecimiento exponencial

text: Resumen Antecedentes y objetivos: La pandemia del coronavirus COVID-19 ha provocado un confinamiento indefinido. Una posible consecuencia de esta situación es un retraso en los procedimientos asistenciales de las patologías comunes. El objetivo de este estudio es estimar el hipotético impacto en la supervivencia que tendría el aumento del tamaño tanto para los carcinomas de células escamosas (CCE) como de los melanomas. Material y Método: Estudio observacional retrospectivo de cohortes multicéntrico. Se desarrolló un modelo de crecimiento exponencial para cada tumor basado en el tiempo de evolución que refiere el paciente. Resultados: Se incluyeron un total de 200 pacientes con CCEs localizados en la cabeza y el cuello y 1000 pacientes con melanoma cutáneo. Se calculó una curva de crecimiento exponencial para cada tumor y se estimó el tamaño del tumor tras 1, 2 y 3 mes tras el diagnóstico. En la muestra, los CCE mayores de 4 cm o >6 mm de grosor (definidos como T3) pasaron de 83 (41.5%) en el grupo de estudio real a una estimación de 58,5%, 70,5% y 72% tras 1, 2 y 3 meses de retraso quirúrgico estimado. Se estimó una disminución de la supervivencia específica de enfermedad (SEE) de un 6,2%, 8,2% y 5,2% a los 2, 5 y 10 años, respectivamente, tras tres meses de retraso. Para los melanomas, los melanomas ultragruesos (>6 mm) pasaron del 6,9% en el grupo de estudio al 21,9%, 30,2% y 30,2% tras 1, 2 y 3 meses de demora. La SEE a los 5 y 10 años del grupo de estudio descendió un 14,4% en ambos tiempos. Conclusiones: En ausencia de un adecuado diagnóstico y tratamiento de los pacientes con CCE y melanoma en la actual situación de confinamiento en España, podemos llegar a asistir a un considerable aumento de los casos de CCE y melanomas gruesos y de gran tamaño. Se deben fomentar los esfuerzos para promocionar la autoexploración y facilitar el acceso a los dermatólogos para no aumentar la demora de estos pacientes. Abstract Background and objectives: Spain is in a situation of indefinite lockdown due to the ongoing coronavirus disease 2019 (COVID-19) pandemic. One of the consequences of this lockdown is delays in medical and surgical procedures for common diseases. The aim of this study was to model the impact on survival of tumor growth caused by such delays in patients with squamous cell carcinoma (SCC) and melanoma. Material and methods: Multicenter, retrospective, observational cohort study. We constructed an exponential growth model for both SCC and melanoma to estimate tumor growth between patient-reported onset and surgical excision at different time points. Results: Data from 200 patients with SCC of the head and neck and 1000 patients with cutaneous melanoma were included. An exponential growth curve was calculated for each tumor type and we estimated tumor size after 1, 2, and 3 months of potential surgical delay. The proportion of patients with T3 SCC (diameter > 4 cm or thickness > 6 mm) increased from 41.5% (83 patients) in the initial study group to an estimated 58.5%, 70.5%, and 72% after 1, 2, and 3 months of delay. Disease-specific survival at 2, 5, and 10 years in patients whose surgery was delayed by 3 months decreased by 6.2%, 8.2%, and 5.2%, respectively. The proportion of patients with ultrathick melanoma (> 6 mm) increased from 6.9% in the initial study group to 21.9%, 30.2%, and 30.2% at 1, 2, and 3 months. Five- and 10-year disease-specific survival both decreased by 14.4% in patients treated after a potential delay of 3 months. Conclusions: In the absence of adequate diagnosis and treatment of SCC and melanoma in the current lockdown situation in Spain, we can expect to see to a considerable increase in large and thick SCCs and melanomas. Efforts must be taken to encourage self-examination and facilitate access to dermatologists in order to prevent further delays.


title: Toward antiviral therapy/prophylaxis for rhinovirus‐induced exacerbations of chronic obstructive pulmonary disease: challenges, opportunities, and strategies

text: Chronic obstructive pulmonary disease (COPD) is a life‐threatening lung illness characterized by persistent and progressive airflow limitation. Exacerbations of COPD contribute to the severity of this pathology and accelerate disease progression. To date, pharmacological treatment of both stable COPD patients and patients experiencing exacerbations is mainly symptomatic with bronchodilators and steroids as the mainstay of therapy. Bacteria trigger such exacerbations in a number of cases; hence, antibiotics might be included in the treatment as well. Several respiratory viruses are frequently detected in sputum from patients during COPD exacerbations. These include influenza viruses, respiratory syncytial virus, and, most often, rhinoviruses. In this review, we discuss the potential use of an anti‐rhinovirus drug for the treatment and prophylaxis of rhinovirus‐induced COPD exacerbations and the path forward toward the development and use of such a drug. Copyright © 2015 John Wiley & Sons, Ltd.


title: Prevalence of adenovirus in children with acute respiratory tract infection in Lanzhou, China

text: BACKGROUND: Human adenovirus (HAdV) is an important agent causing respiratory tract infection in children. Information on the epidemiological and clinical features of HAdV is limited in children with acute respiratory tract infections (ARTIs) in China, especially those of a novel genotype, Ad55. METHODS: In total, 1169 nasopharyngeal aspirates were collected from children younger than 14 years with ARTIs between November 2006 and November 2009. The polymerase chain reaction (PCR) was used to screen HAdVs. All PCR-positive products were sequenced. RESULTS: 74 of 1169 (6.33%) specimens were positive for HAdVs. Among positive cases, AdV3 (58/74) was detected most frequently, followed by AdV11 (10/74), AdV2 (2/74), AdV7 (2/69), AdV6 (1/74), and AdV1 (1/74). AdV55 was found in one case. The incidence of HAdV infection peaked in children aged 3–7 years. The most common clinical diagnosis was upper respiratory infection, and the most common syndrome was fever and cough.The comparison of HAdV and RSV group revealed that Children infected with group AdV were significant older than children infected with group RSV, had more fever but less frequently wheezing, and cough, crackles, and cyanosis, The duration of hospitalization between the AdV group and RSV group was not significant, but a greater frequency of LRTIs was observed in RSV group. CONCLUSIONS: HAdV is an important viral agent in children with ARTIs in Lanzhou City, China. Multiple HAdV serotypes co-circulated with Ad3, which was predominant in this 3-year study. The novel AdV55 genotype was found in one case. No fixed seasonal rhythm could be identified.


Exercise stress testing: Time to restart in nuclear cardiology?


Complex Scenario of Homotypic and Heterotypic Zika Virus Immune Enhancement


title: Place de l’assistance extracorporelle en pathologie respiratoire

text: Résumé L’oxygénation extracorporelle ou extra-corporeal membrane oxygenation (ECMO) constitue une suppléance de l’échangeur respiratoire (oxygénation et décarboxylation) pour laquelle un regain d’intérêt survient depuis quelques années. Cet intérêt a été amplifié par la pandémie grippale H1N1 mais est également suscité par des améliorations technologiques significatives qui autorisent aujourd’hui la mise en œuvre chez des patients éveillés et mobiles. Mais c’est essentiellement l’émergence d’études randomisées comme dans le syndrome de détresse respiratoire de l’adulte avec des résultats encourageants qui valorisent cette thérapeutique. Connaître la terminologie et les principes généraux de cette technique ainsi que les situations et perspectives futures auxquelles le pneumologue et le réanimateur peuvent être confrontés fait l’objet de cette revue générale. Deux points seront en particulier évoqués tels que les perspectives d’épuration extracorporelle du CO2 dans le cadre des décompensations respiratoires hypercapniques et les situations de suppléances au cours de la transplantation pulmonaire depuis la période préopératoire, jusqu’à la phase postopératoire. Summary Extra-corporeal membrane oxygenation (ECMO) effectively replaces the lung in providing oxygenation and carbon dioxide (CO2) removal. For some years, and in parallel to the H1N1 influenza pandemic, this technique has gained interest in relation to significant technological improvements, leading to new concepts of “awake and mobile ECMO” or rehabilitation with ECMO. Finally, the publication of randomized controlled trials giving encouraging results in the adult respiratory distress syndrome (ARDS) has helped to validate this technique and further studies are warranted. This general review aims to outline the definition, classification and principles of ECMO and to give some current information about the indications and possibilities of the technique to the pulmonologist and intensivist. Further possible uses for this technique include extra-corporeal removal of CO2 during hypercapnic respiratory failure and assistance during lung transplantation from the preoperative to the early postoperative period.


title: Management Guidelines for Obstetric Patients and Neonates Born to Mothers With Suspected or Probable Severe Acute Respiratory Syndrome (SARS)

text: Abstract Objective This document summarizes the limited experience of SARS in pregnancy and suggests guidelines for management. Outcomes Cases reported from Asia suggest that maternal and fetal outcomes are worsened by SARS during pregnancy. Evidence Medline was searched for relevant articles published in English from 2000 to 2007. Case reports were reviewed and expert opinion sought. Values Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care. Sponsors The Society of Obstetricians and Gynaecologists of Canada. Recommendations 1. All hospitals should have infection control systems in place to ensure that alerts regarding changes in exposure risk factors for SARS or other potentially serious communicable diseases are conveyed promptly to clinical units, including the labour and delivery unit. (III-C) 2. At times of SARS outbreaks, all pregnant patients being assessed or admitted to the hospital should be screened for symptoms of and risk factors for SARS. (III-C) 3. Upon arrival in the labour triage unit, pregnant patients with suspected and probable SARS should be placed in a negative pressure isolation room with at least 6 air exchanges per hour. All labour and delivery units caring for suspected and probable SARS should have available at least one room in which patients can safely labour and deliver while in need of airborne isolation. (III-C) 4. If possible, labour and delivery (including operative delivery or Caesarean section) should be managed in a designated negative pressure isolation room, by designated personnel with specialized infection control preparation and protective gear. (III-C) 5. Either regional or general anaesthesia may be appropriate for delivery of patients with SARS. (III-C) 6. Neonates of mothers with SARS should be isolated in a designated unit until the infant has been well for 10 days, or until the mother’s period of isolation is complete. The mother should not breastfeed during this period. (III-C) 7. A multidisciplinary team, consisting of obstetricians, nurses, pediatricians, infection control specialists, respiratory therapists, and anaesthesiologists, should be identified in each unit and be responsible for the unit organization and implementation of SARS management protocols. (III-C) 8. Staff caring for pregnant SARS patients should not care for other pregnant patients. Staff caring for pregnant SARS patients should be actively monitored for fever and other symptoms of SARS. Such individuals should not work in the presence of any SARS symptoms within 10 days of exposure to a SARS patient. (III-C) 9. All health care personnel, trainees, and support staff should be trained in infection control management and containment to prevent spread of the SARS virus. (III-A) 10. Regional health authorities in conjunction with hospital staff should consider designating specific facilities or health care units, including primary, secondary, or tertiary health care centres, to care for patients with SARS or similar illnesses. (III-A)


Coordination internationale nécessaire et défense de l'OMS face à la pandémie


title: The Rho ADP-ribosylating C3 exoenzyme binds cells via an Arg–Gly–Asp motif

text: The Rho ADP-ribosylating C3 exoenzyme (C3bot) is a bacterial protein toxin devoid of a cell-binding or -translocation domain. Nevertheless, C3 can efficiently enter intact cells, including neurons, but the mechanism of C3 binding and uptake is not yet understood. Previously, we identified the intermediate filament vimentin as an extracellular membranous interaction partner of C3. However, uptake of C3 into cells still occurs (although reduced) in the absence of vimentin, indicating involvement of an additional host cell receptor. C3 harbors an Arg–Gly–Asp (RGD) motif, which is the major integrin-binding site, present in a variety of integrin ligands. To check whether the RGD motif of C3 is involved in binding to cells, we performed a competition assay with C3 and RGD peptide or with a monoclonal antibody binding to β1-integrin subunit and binding assays in different cell lines, primary neurons, and synaptosomes with C3-RGD mutants. Here, we report that preincubation of cells with the GRGDNP peptide strongly reduced C3 binding to cells. Moreover, mutation of the RGD motif reduced C3 binding to intact cells and also to recombinant vimentin. Anti-integrin antibodies also lowered the C3 binding to cells. Our results indicate that the RGD motif of C3 is at least one essential C3 motif for binding to host cells and that integrin is an additional receptor for C3 besides vimentin.


title: Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality

text: Abstract Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world.


Time to ‘Buddy Up’ – Simple Strategies to Support Oncologists During the Covid-19 Pandemic


Balancing public health and private wealth: lessons on climate inaction from the COVID‐19 pandemic – a report from the International Society of Dermatology Climate Change Committee


title: The problems with so-called immunity tests

text: Initial antibody testing surveys suggest more people have been infected than we thought. But we need to be cautious about these results, reports Michael Le Page


title: Passive immune transfer in puppies

text: Abstract The puppy, born without immunoglobulins G (IgG), acquires a passive systemic immunity thanks to colostrum intake during the two first days of life. The quality of passive immune transfer (i.e. blood IgG concentration at two days of age), highly variable between litters and between puppies within litters, depends mainly on the time elapsed between birth and ingestion of colostrum, with limited influence of colostrum IgG concentration. Deficit in passive immune transfer, impacting puppy’s health and neonatal mortality rate, can be indirectly diagnosed through blood gammaglutamyltransferases assay and evaluation of growth rate over the two first days of life. In the absence of maternal colostrum, few homo- and heterospecific immune sources are available and canine colostrum banking remains the optimal solution. Whereas passive immune transfer is crucial for survival during the neonatal period, it later interferes with response to vaccination. In addition to systemic passive immune transfer, maternal antibodies (mainly IgA) would provide local (digestive) immunity, ensuring mid-term protection of the puppies’ gut together with probably long term training of the digestive immune system.


title: Mild acute inflammatory stimulation induces transient negative mood

text: Abstract Objective This study aims to assess the mood changes induced by mild acute inflammatory stimulation (typhoid vaccination). Methods Using a double blind study design, 26 healthy volunteers underwent baseline assessments of mood, financial strain and work stress and were randomised to injection of Salmonella typhi vaccine or placebo injection. Mood, symptoms and body temperature was assessed by a modified version of the Profile of Mood States at 1, 2, 3, 4, 6 and 8 h post injection. Results Typhoid vaccination induces no increases in physical symptoms or temperature. Mood improved over the day in the placebo but not in the vaccine condition. Negative changes in mood following injection were correlated with chronic stress (financial strain) in the vaccination condition (r=−.65, P<.025). Conclusion A mild acute inflammatory stimulus induces transient negative mood, and responses were modulated by chronic stress. Implications for depressed mood in physical illness are discussed.


title: 4 Communicable Diseases

text: Publisher Summary In a world of rapid international transport and contact between populations, systems are needed to monitor the potential explosive spread of pathogens that may be transferred from their normal habitat. The potential for the international spread of new or reinvigorated infectious diseases constitute threat to mankind akin to ecological and other man-made disasters. Public health has addressed the issues of communicable disease as one of its key issues in protecting individual and population health. Methods of intervention include classic public health through sanitation, immunization, and well beyond that into nutrition, education, case finding, and treatment, and changing human behavior. The knowledge, attitudes, beliefs, and practices of policy makers, health care providers, and parents is as important in the success of communicable disease control as are the technology available and methods of financing health systems. Together, these encompass the broad programmatic approach of the New Public Health to control of communicable diseases.


title: Complementary and alternative medicine for the treatment of bronchiolitis in infants: A systematic review

text: BACKGROUND: Bronchiolitis is a common cause of hospitalization among infants. The limited effectiveness of conventional medication has prompted the use of complementary and alternative medicine (CAM) as alternative or adjunctive therapy for the management of bronchiolitis. AIMS: To determine the effectiveness and safety of CAM for the treatment of bronchiolitis in infants aged less than 2 years. METHODS: A systematic electronic search was performed in Medline, Embase, CINAHL, AMED, and Cochrane Central Register of Controlled Trials (CENTRAL) from their respective inception to June 30, 2016 for studies evaluating CAM as an intervention to treat bronchiolitis in infants (1 month to 2 years of age). The CAM could be any form of treatment defined by the National Center for Complementary and Integrative Health (NCCIH) and was utilized either as a single agent or adjunctive therapy. The predefined primary outcome was length of hospital stay. Secondary outcomes were time to resolution of bronchiolitis symptoms, adverse events, and all other clinical outcomes reported by the included studies. RESULTS: The review identified 11 studies (8 randomized controlled trials and 3 cohort studies) examining four herbal preparations and four supplements used either as adjunctive or alternative therapy for bronchiolitis in 904 infants. Most studies were of moderate quality. Among six studies reporting on length of stay, a significant benefit was found for Chinese herbal medicine compared to ribavirin in one cohort study (n = 66) and vitamin D compared to placebo in one randomized controlled trial (n = 89). Studies of Chinese herbal medicine (4 studies, n = 365), vitamin D (1 study, n = 89), N-acetylcysteine (1 study, n = 100), and magnesium (2 studies, n = 176) showed some benefits with respect to clinical severity scores, oxygen saturation, and other symptoms, although data were sparse for any single intervention and the outcomes assessed and reported varied across studies. Only five studies reported on adverse events; no serious adverse events were reported. CONCLUSIONS: Among 11 studies examining the effect of CAM on inpatients with bronchiolitis, six reported on the review’s primary outcome of length of hospital stay. In general, findings did not show a significant benefit associated with the primary outcome. Preliminary evidence indicated that Chinese herbal medicine mixtures, vitamin D, N-acetylcysteine, and magnesium might be useful in managing the symptoms of bronchiolitis. However, the evidence was not sufficient or rigorous enough to formulate recommendations for the use of any CAM. Among studies that reported adverse events, no serious harms were noted.


title: Health care facility and community strategies for patient care surge capacity()()

text: Recent terrorist and epidemic events have underscored the potential for disasters to generate large numbers of casualties. Few surplus resources to accommodate these casualties exist in our current health care system. Plans for “surge capacity” must thus be made to accommodate a large number of patients. Surge planning should allow activation of multiple levels of capacity from the health care facility level to the federal level. Plans should be scalable and flexible to cope with the many types and varied timelines of disasters. Incident management systems and cooperative planning processes will facilitate maximal use of available resources. However, resource limitations may require implementation of triage strategies. Facility-based or “surge in place” solutions maximize health care facility capacity for patients during a disaster. When these resources are exceeded, community-based solutions, including the establishment of off-site hospital facilities, may be implemented. Selection criteria, logistics, and staffing of off-site care facilities is complex, and sample solutions from the United States, including use of local convention centers, prepackaged trailers, and state mental health and detention facilities, are reviewed. Proper pre-event planning and mechanisms for resource coordination are critical to the success of a response.


title: Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity

text: Abstract Actinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis - cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulated caspase-1 and its two activators: IFI16 and NLRP1, however, caspase-1 activation was not detected. A549 cells may have been primed for pyroptosis, with the absence of a crucial trigger. The investigation of additional innate immunity elements revealed that A + N (or camptothecin) stimulated the expression of NLRX1, STING (stimulator of interferon genes) and two antiviral proteins, IFIT1 and IFIT3. IFI16 and caspase-1 are coded by p53-regulated genes which led us to investigate regulation of NLRP1, NLRX1, STING, IFIT1 and IFIT3 in p53-dependent mode. The upregulation of NLRP1, NLRX1 and STING was attenuated in p53 knockdown cells. The upsurge of the examined genes, and activation of p53, was inhibited by C16, an inhibitor of PKR kinase. PKR was tested due to its ability to phosphorylate p53 on Ser392. Surprisingly, C16 was active even in PKR knockdown cells. The ability of C16 to prevent activation of p53 and expression of innate immunity genes may be the source of its strong anti-inflammatory action. Moreover, cells exposed to A + N can influence neighboring cells in paracrine fashion, for instance, they shed ectodomain of COL17A1 protein and induce, in p53-dependent mode, the expression of gene for interleukin-7. Further, the activation of p53 also spurred the expression of SOCS1, an inhibitor of interferon triggered STAT1-dependent signaling. We conclude that, stimulation of p53 primes cells for the production of interferons (through upregulation of STING), and may activate negative-feedback within this signaling system by enhancing the production of SOCS1.


title: Prolonged fecal shedding of SARS-CoV-2 in pediatric patients. A quantitative evidence synthesis

text: OBJECTIVE: To investigate differences in viral shedding in respiratory and fecal samples from children with COVID-19. METHODS: We searched PubMed, SCOPUS, Embase and Web of Science databases to identify pediatric studies comparing the pattern of fecal and respiratory shedding of SARS-CoV-2 RNA. Summary estimates were calculated using random-effects models. RESULTS: Four studies reporting data from 36 children were included. A higher proportion of children had viral shedding in stools after 14 days of symptoms onset compared to respiratory samples (RR= 3.2, 95%CI 1.2 to 8.9, I2 = 51%). Viral RNA shedding was longer in fecal samples with a mean difference of approximately 9 days (Mean Difference = 8.6, 95%CI 1.7 to 15.4, I2 = 77%) compared with respiratory samples. CONCLUSION: SARS-CoV-2 shedding seems to be present in feces for a longer time than in the respiratory tract of children. Although fecal SARS-CoV-2 presence in feces do not confirm its transmissibility, the high and fast spread of the COVID-19 disease worldwide indicate other transmission routes are also plausible.


title: Effects of aging on T cell function

text: Immunosenescence influences many components of the immune system. Most importantly, profound changes in T cell function are evident in older individuals. The impact of aging on specific T cell subsets has been difficult to examine, but recent advances in murine model systems and new insights into T cell function have allowed for the more precise examination of how T cell responses change with aging. Importantly, recent studies have shown that age-related enhancement of both Th17 generation and regulatory T cell function may contribute to significant changes in immune function. In this review, we summarize the current views on how aging influences the factors that impact T cell function and how this can affect the immune response to infections, vaccinations, and tumors.


title: Lycorine reduces mortality of human enterovirus 71-infected mice by inhibiting virus replication

text: Human enterovirus 71 (EV71) infection causes hand, foot and mouth disease in children under 6 years old and this infection occasionally induces severe neurological complications. No vaccines or drugs are clinical available to control EV71 epidemics. In present study, we show that treatment with lycorine reduced the viral cytopathic effect (CPE) on rhabdomyosarcoma (RD) cells by inhibiting virus replication. Analysis of this inhibitory effect of lycorine on viral proteins synthesis suggests that lycorine blocks the elongation of the viral polyprotein during translation. Lycorine treatment of mice challenged with a lethal dose of EV71 resulted in reduction of mortality, clinical scores and pathological changes in the muscles of mice, which were achieved through inhibition of viral replication. When mice were infected with a moderate dose of EV71, lycorine treatment was able to protect them from paralysis. Lycorine may be a potential drug candidate for the clinical treatment of EV71-infected patients.


title: Exploring disaster resilience within the hotel sector: A systematic review of literature

text: Abstract Within the tourism industry, the hotel sector's vulnerabilities are multi-faceted. This literature discussion scrutinizes how disaster and resilience is framed for the tourism sector, and, more specifically, how the concepts can be applied to the hotel sector. A synthesis of the literature points to the importance of prioritizing disaster resilience building for the hotel sector. The body of literature regarding disasters, tourism, and more specifically hotels, has increased over the last 20 years, still improvements in the hotel sector's disaster preparedness and do not appear to be on the same trajectory. Illustrating the predicament of the contemporary hotel industry serves to open a discussion about the value of building resiliency to disaster for hotels. As the numbers of people affected by disasters grows, the importance of providing actionable information to limit the severity of these events on communities also escalates in pace.


title: Modelling Emerging Viral Epidemics for Public Health Protection

text: Mathematical models when applied to infectious disease data can provide extremely useful insights into the possible future impacts of potential emerging epidemics and how they might be best controlled or mitigated. Modelling, which is like any other hypothesis-driven approach, aims to develop a better understanding of biological phenomena. However, diseases processes generally, and particularly those related to transmission, will in many cases be imperfectly understood or too complex to systematically describe, so models will necessarily be simplifications of the overall system. It is essential, therefore, that models are designed carefully and used appropriately. Key to this is identifying what specific questions a model might be expected to answer and what data is available to inform the model. A particular type of model might be fine for one particular situation but highly inappropriate for another. It is also important to appreciate and communicate what simplifications and assumptions have had to be made and how this might affect the robustness of the modelling results. It is also particularly important to understand that models frequently make what can be hidden assumptions about underlying processes because of the way they have been constructed and these assumptions also need to be carefully considered and made explicit, particularly for non-expert audiences. This chapter, therefore, provides a brief introduction to some of these aspects of epidemic modelling for those that might be less familiar with them.


title: Immunizations in the United States: A Rite of Passage

text: Today, vaccination is a cornerstone of pediatric preventive health care and a rite of passage for nearly all of the approximately 11,000 infants born daily in the United States. This article reviews the US immunization program with an emphasis on its role in ensuring that vaccines are effective, safe, and available and highlights several new vaccines and recommendations that will affect the health of children and adolescents and the practice of pediatric medicine in future decades.


title: Disease reservoirs: from conceptual frameworks to applicable criteria

text: Central to the One Health approach and any disease eradication program is the question of whether a pathogen has a non-human reservoir. Despite well-established conceptual frameworks that define a reservoir of infection, empirical characterization of reservoirs often remains controversial, challenging and sometimes misleading. What is essentially missing are applicable requirements that standardize the use of the term ‘reservoir of infection’ across multiple disciplines. We propose an empirical framework, considering maintenance and feasible transmission of a pathogen, to standardize the acceptance of a disease reservoir across multiple disciplines. We demonstrate the intended use of these requirements by applying them to different diseases that are known to infect both humans and animals.


title: COVID-19: clinical challenges in Dutch Geriatric Psychiatry

text: The COVID-19 pandemic has changed everyday life tremendously in a short period of time. After a brief timeline of the Dutch situation and our management strategy to adapt geriatric mental health care, we present a case-series to illustrate the specific challenges for geriatric psychiatrists.


title: Methods of Measuring Compliance with Transmission-Based Isolation Precautions: Comparison of Paper-Based and Electronic Data Collection

text: BACKGROUND: Decreasing transmission of resistant organisms in hospitals is a key goal of infection prevention plans. Studies have shown that health care worker (HCW) compliance with isolation precautions is inadequate. Direct observation of HCW behavior for measuring adherence is considered the “gold standard” but is labor intensive, requiring the collection and analysis of a large volume of observations. METHODS: Two methods of data collection were evaluated to asses HCW compliance: a manual method using a paper form (PF) with subsequent data entry into a database, and an electronic method using a web-based form (WBF) with real-time data recording. Observations were conducted at four hospitals (2,065 beds) to assess availability of gloves, gowns and masks, isolation sign postings, and HCW isolation practices. RESULTS: A total of 13,878 isolation rooms were observed in 2009. The median number of rooms observed/day for PF and WBF were 61 and 60 and the mean observation times/room were 149sec and 60sec, respectively. The WBF provided a time savings of 89 sec/room. CONCLUSIONS: Simple electronic forms can significantly decrease resources needed to monitor HCW adherence to hospital policies. The WBF decreased observation time by 60%, allowing for an increase in frequency and expansion of surveillance activities.


title: Disability through COVID‐19 pandemic: Neurorehabilitation cannot wait

text: Coronavirus disease 2019 (CoViD‐19) pandemic is strongly impacting all domains of our healthcare systems, including rehabilitation. In Italy, the first hit European country, medical activities were postponed to allow shifting of staff and facilities to intensive care, with neurorehabilitation limited to time‐dependent diseases,(1) including CoViD‐19 complications.(2,3) Hospital access to people with chronic neurodegenerative conditions such as multiple sclerosis, movement disorders or dementia, more at risks of serious consequences from the infection,(4) has been postponed. Patients also seek less for hospital care, with over 50% reduced stroke admissions as from an Italian survey,(5) possibly in fear of being infected or denied to see their families after being hospitalized. This situation can be bearable only for a short time, as any initial freezing reaction to a danger.


title: Abnormal liver function tests predict transfer to intensive care unit and death in COVID‐19

text: BACKGROUND: The pandemic of coronavirus disease 2019 (COVID‐19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID‐19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non‐critically ill patients with COVID‐19. METHODS: In this multicenter, retrospective study, we collected data about 565 inpatients with COVID‐19. Data on LFTs were collected at admission and every 7±2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20vs8%; p<0.001), acute kidney injury (22vs13%, p=0.009), need for mechanical ventilation (14vs6%; p=0.005), and mortality (21vs11%; p=0.004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR=3.53; p<0.001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID‐19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.


title: U.S. county level analysis to determine If social distancing slowed the spread of COVID-19

text: OBJECTIVE. To analyze the effectiveness of social distancing in the United States (U.S.). METHODS. A novel cell-phone ping data was used to quantify the measures of social distancing by all U.S. counties. RESULTS. Using a difference-in-difference approach results show that social distancing has been effective in slowing the spread of COVID-19. CONCLUSIONS. As policymakers face the very difficult question of the necessity and effectiveness of social distancing across the U.S., counties where the policies have been imposed have effectively increased social distancing and have seen slowing the spread of COVID-19. These results might help policymakers to make the public understand the risks and benefits of the lockdown.


title: Aminopeptidase activity in human nasal mucosa

text: Abstract Background: Aminopeptidases activate bradykinin and degrade many inflammatory peptides. Objective: The objective of this study was to identify the types of aminopeptidase activities in human nasal mucosa. Methods: Human nasal mucosa was homogenized (n = 12), and cytoplasmic (S2) and membrane-rich (P2) fractions were obtained. Several aminopeptidase (Ap) activities were defined by (1) substrate specificity with leucine-enkephalin (leu-Ap) and alanine-nitroanilide (ala-Ap), (2) inhibitor studies with puromycin and bestatin, (3) enzyme activity histochemistry (zymography), (4) immunohistochemistry, and (5) gel electrophoresis. Human volunteers had methacholine, histamine, and allergen nasal provocations to determine the mechanisms controlling nasal aminopeptidase secretion in vivo. Results: P2 was the largest reservoir of puromycin-resistant aminopeptidase activity (630 pmol leu-enk/min/mg protein). S2 contained 32 pmol leu-enk/min/mg activity, with 80% representing puromycin-resistant activity and 20% puromycin-sensitive aminopeptidase (PS-Ap). Ala-Ap was detected in both P2 and S2 fractions and was localized by zymography to epithelial and gland cells. Anti–rat brain–soluble PS-Ap IgG detected immunoreactive material in epithelium, glands, and endothelium. In nasal provocation studies, leu-AP correlated with glandular exocytosis but not vascular leak. Conclusions: The predominant aminopeptidase in human nasal epithelial and submucosal gland cells was membrane-bound puromycin-resistant aminopeptidase. A novel soluble puromycin-resistant aminopeptidase and lower amounts of soluble PS-Ap were also detected. (J Allergy Clin Immunol 1998;102:741-50.)


Coronavirus (COVID-19), First Indication of Efficacy of Gene-Eden-VIR/Novirin in SARS-CoV-2 Infections


Respiratory infections in the Asia‐Pacific region: Problems and cautious optimism


title: Phylogenetic and epidemic modeling of rapidly evolving infectious diseases

text: Abstract Epidemic modeling of infectious diseases has a long history in both theoretical and empirical research. However the recent explosion of genetic data has revealed the rapid rate of evolution that many populations of infectious agents undergo and has underscored the need to consider both evolutionary and ecological processes on the same time scale. Mathematical epidemiology has applied dynamical models to study infectious epidemics, but these models have tended not to exploit – or take into account – evolutionary changes and their effect on the ecological processes and population dynamics of the infectious agent. On the other hand, statistical phylogenetics has increasingly been applied to the study of infectious agents. This approach is based on phylogenetics, molecular clocks, genealogy-based population genetics and phylogeography. Bayesian Markov chain Monte Carlo and related computational tools have been the primary source of advances in these statistical phylogenetic approaches. Recently the first tentative steps have been taken to reconcile these two theoretical approaches. We survey the Bayesian phylogenetic approach to epidemic modeling of infection diseases and describe the contrasts it provides to mathematical epidemiology as well as emphasize the significance of the future unification of these two fields.


title: How to handle patients with autoimmune rheumatic and inflammatory bowel diseases in the COVID-19 era: An expert opinion

text: • A correct patient risk stratification is of paramount importance for the proper management of economic and human resources. • It's fundamental to prioritize clinical trials evaluating dosing, prophylaxis, and treatment with immunosuppressant in COVID-19 in order to avoid either an overuse and a treatment shortage. • Future controlled studies may highlight in our patients a potential preventive role of immunosuppressant therapies in the development of severe forms of Covid-19. • Despite the overall risk of infection in rheumatic and gastroenterological diseases a conclusive association between these diseases and COVID −19 remains questionable.


title: The plasticity of inflammatory monocyte responses to the inflamed central nervous system

text: Abstract Over the last three decades it has become increasingly clear that monocytes, originally thought to have fixed, stereotypic responses to foreign stimuli, mediate exquisitely balanced protective and pathogenic roles in disease and immunity. This balance is crucial in core functional organs, such as the central nervous system (CNS), where minor changes in neuronal microenvironments and the production of immune factors can result in significant disease with fatal consequences or permanent neurological sequelae. Viral encephalitis and multiple sclerosis are examples of important human diseases in which the pathogenic contribution of monocytes recruited from the bone marrow plays a critical role in the clinical expression of disease, as they differentiate into macrophage or dendritic cells in the CNS to carry out effector functions. While antigen-specific lymphocyte populations are central to the adaptive immune response in both cases, in viral encephalitis a prominent macrophage infiltration may mediate immunopathological damage, seizure induction, and death. However, the autoimmune response to non-replicating, non-infectious, but abundant, self antigen has a different disease progression, associated with differentiation of significant numbers of infiltrating monocytes into dendritic cells in the CNS. Whilst a predominant presence of macrophages or dendritic cells in the inflamed CNS in viral encephalitis or multiple sclerosis is well described, the way in which the inflamed CNS mobilizes monocytes in the bone marrow to migrate to the CNS and the key drivers that lead to these specific differentiation pathways in vivo are not well understood. Here we review the current understanding of factors facilitating inflammatory monocyte generation, migration and entry into the brain, as well as their differentiation towards macrophages or dendritic cells in viral and autoimmune disease in relation to their respective disease outcomes.


title: Structural analysis of the conformational domains involved in neutralization of bovine coronavirus using deletion mutants of the spike glycoprotein S1 subunit expressed by recombinant baculoviruses

text: Abstract Two conformation-dependent neutralizing epitopes, A and B, have been mapped to the S1 subunit of the S spike glycoprotein of bovine coronavirus (BCV). In order to characterize the structure of these antigenic sites, we constructed a series of cDNA clones encoding deleted or truncated S1 derivatives and expressed the modified genes in insect cells using recombinant baculoviruses. Monoclonal antibodies directed against epitopes A and B recognized only the mutant S1 polypeptides containing amino acids 324–720, as demonstrated by immunoprecipitation and Western blot analysis in the absence of β-mercaptoethanol. In addition, two domains within this region were identified and only mutants containing both domains were immunoreactive, indicating that both were critical in the formation of the antigenic determinants. One domain was localized between residues 324 and 403 and the other at residues 517–720. Deletion of either domain inhibited extracellular secretion of the mutant proteins whereas mutants containing both or none of the domains were secreted efficiently. This observation suggests a vital function of the native conformation of the S1 protein in both antigenic structure and intracellular transport. Antigenic determinants A and B were not distinguished, but these determinants appeared to require both domains for epitope formation. Our results suggest that the antigenic determinants formed by two domains are likely associated with the probable polymorphic region of the BCV S1 subunit.


title: Engineering passive immunity in transgenic mice secreting virus-neutralizing antibodies in milk

text: Protection against enteric infections can be provided by the oral administration of pathogen-neutralizing antibodies. To provide passive immunity, 18 lines of transgenic mice secreting a recombinant monoclonal antibody (Mab) neutralizing transmissible gastroenteritis coronavirus (TGEV) into the milk were generated. The genes encoding a chimeric Mab with the variable modules of the murine TGEV-specific Mab 6A.C3 and the constant modules of a human IgG(1), isotype Mab were expressed under the control of regulatory sequences derived from the whey acidic protein, which is an abundant milk protein. The Mab 6A.C3 binds to a highly conserved epitope present in coronaviruses of several species, which does not allow the selection of neutralization escape mutants. Antibody expression titers of 10(6) were obtained in the milk of transgenic mice that reduced TGEV infectivity 10(6)-fold. The antibody was synthesized at high levels throughout lactation. Integration of matrix attachment region sequences with the antibody genes led to a 20- to 10,000-fold increase in the antibody titer in 50% of the transgenic animals. Antibody expression levels were transgene copy number independent and related to the site of integration. The generation of transgenic animals producing virus neutralizing antibodies in milk could provide an approach to protection against neonatal infections of the enteric tract.


title: Forecasting the timeframe of coronavirus and human cells interaction with reverse engineering

text: Abstract In December 2019, an atypical pneumonia invaded the city of Wuhan, China, and the causative agent of this disease turned out to be a new coronavirus. In January 2020, the World Health Organization named the new coronavirus 2019-nCoV and subsequently it is referred to as SARS-CoV2 and the related disease as CoViD-19 [9]. Very quickly, the epidemic led to a pandemic and it is now a worldwide emergency requiring the creation of new antiviral therapies and a related vaccine. The purpose of this article is to review and investigate further the molecular mechanism by which the SARS-CoV2 virus infection proceeds via the formation of a hetero-trimer between its protein S, the ACE2 receptor and the B0AT1 protein, which is the “entry receptor” for the infection process involving membrane fusion [10]. A reverse engineering process uses the formalism of the Hill function to represent the functions related to the dynamics of the biochemical interactions of the viral infection process. Then, using a logical evaluation of viral density that measures the rate at which the cells are hijacked by the virus (and they provide a place for the virus to replicate) and considering the “time delay” given by the interaction between cell and virus, the expected duration of the incubation period is predicted. The conclusion is that the density of the virus varies from the “exposure time” to the “interaction time” (virus-cells). This model can be used both to evaluate the infectious condition and to analyze the incubation period. Background The ongoing threat of the new coronavirus SARS-CoV2 pandemic is alarming and strategies for combating infection are highly desired. This RNA virus belongs to the β-coronavirus genus and is similar in some features to SARS-CoV. Currently, no vaccine or approved medical treatment is available. The complex dynamics of the rapid spread of this virus can be demonstrated with the aid of a computational framework. Methods A mathematical model based on the principles of cell-virus interaction is developed in this manuscript. The amino acid sequence of S proein and its interaction with the ACE-2 protein is mimicked with the aid of Hill function. The mathematical model with delay is solved with the aid of numerical solvers and the parametric values are obtained with the help of MCMC algorithm. Results A delay differential equation model is developed to demonstrate the dynamics of target cells, infected cells and the SARS-CoV2. The important parameters and coefficients are demonstrated with the aid of numerical computations. The resulting thresholds and forecasting may prove to be useful tools for future experimental studies and control strategies. Conclusions From the analysis, I is concluded that control strategy via delay is a promising technique and the role of Hill function formalism in control strategies can be better interpreted in an inexpensive manner with the aid of a theoretical framework.


Narrative medicine: thinking with stories during The Plague


COVID-19 spread: the Italian case


title: Super-spreaders in infectious diseases

text: Summary Early studies that explored host–pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.


title: Colon capsule endoscopy: an innovative method for detecting colorectal pathology during the COVID‐19 pandemic?

text: AIM: The coronavirus pandemic has led to significant challenges for healthcare delivery across the globe. Non‐emergency endoscopic activity in the UK has been postponed, raising concerns of increased delays in the diagnosis of colorectal cancer and a surge in demand once services resume. Measures to mitigate this risk must be considered. METHOD: This paper reviews various investigative modalities for colorectal disease which could be deployed during cessation of colonoscopy services. We focus on colon capsule endoscopy (CCE) due to its relevance during the COVID‐19 pandemic and its ability to triage patients effectively to further endoscopic investigations. RESULTS: CT of the abdomen and pelvis has been suggested as a triage tool while access to colonoscopy is limited. However, CT may lead to the spread of COVID‐19 as patients attend the hospital, and it exposes them to the risks of radiation. Faecal immunochemistry tests have been demonstrated as a good predictor of colonic pathology and could be safely used to risk stratify patients when prioritizing colonoscopy. CCE is a safe and innovative technology for investigating the colon. Procedures can be carried out in the community and can be conducted safely during the coronavirus pandemic. It has been shown to be an accurate detector of colonic neoplasia and can reduce demand for colonoscopy. CONCLUSION: As colonoscopy services resume, they will probably experience high demand leading to further delays for patients. CCE could be used to reduce the number of patients requiring colonoscopy and triage those requiring further endoscopic investigations appropriately.


title: Assessment of temporally-related acute respiratory illness following influenza vaccination

text: Abstract Background A barrier to influenza vaccination is the misperception that the inactivated vaccine can cause influenza. Previous studies have investigated the risk of acute respiratory illness (ARI) after influenza vaccination with conflicting results. We assessed whether there is an increased rate of laboratory-confirmed ARI in post-influenza vaccination periods. Methods We conducted a cohort sub-analysis of children and adults in the MoSAIC community surveillance study from 2013 to 2016. Influenza vaccination was confirmed through city or hospital registries. Cases of ARI were ascertained by twice-weekly text messages to household to identify members with ARI symptoms. Nasal swabs were obtained from ill participants and analyzed for respiratory pathogens using multiplex PCR. The primary outcome measure was the hazard ratio of laboratory-confirmed ARI in individuals post-vaccination compared to other time periods during three influenza seasons. Results Of the 999 participants, 68.8% were children, 30.2% were adults. Each study season, approximately half received influenza vaccine and one third experienced ≥1 ARI. The hazard of influenza in individuals during the 14-day post-vaccination period was similar to unvaccinated individuals during the same period (HR 0.96, 95% CI [0.60, 1.52]). The hazard of non-influenza respiratory pathogens was higher during the same period (HR 1.65, 95% CI [1.14, 2.38]); when stratified by age the hazard remained higher for children (HR 1·71, 95% CI [1.16, 2.53]) but not for adults (HR 0.88, 95% CI [0.21, 3.69]). Conclusion Among children there was an increase in the hazard of ARI caused by non-influenza respiratory pathogens post-influenza vaccination compared to unvaccinated children during the same period. Potential mechanisms for this association warrant further investigation. Future research could investigate whether medical decision-making surrounding influenza vaccination may be improved by acknowledging patient experiences, counseling regarding different types of ARI, and correcting the misperception that all ARI occurring after vaccination are caused by influenza.


title: Optical sensor for berberine utilizing its intrinsic fluorescence enhanced by the formation of inclusion complex with butylated-β-cyclodextrin

text: Abstract An optical sensor for berberine, the basic ingredient of the widely used traditional Chinese medicine Coptis Chinensis, based on its intrinsic fluorescence enhanced by butylated-β-cyclodextrin (HDB-β-CD) immobilized in plasticized poly(vinyl chloride) (PVC) membrane has been developed. The drastic enhancement of fluorescence intensity of berberine was attributed to the formation of an inclusion complex between HDB-β-CD and berberine, which has been utilized as the basis of the fabrication of a berberine-sensitive fluorescence sensor. The proposed sensor was quite distinct from those fluorescent sensors for berberine reported so far which relied upon quenching the fluorescence of the sensing reagent immobilized on membrane by berberine. The response mechanism of optode membrane was discussed in detail from the view of molecular dynamics and the optimum steric configuration of the inclusion complex was presented by molecular dynamics simulation. The analytical performance characteristics of the proposed berberine-sensitive sensor were investigated. The sensor can be applied to the quantification of berberine with a linear range covering from 4.0×10−7 to 2.0×10−5 moll−1 with a detection limit of 8.0×10−8 moll−1. The sensor exhibits excellent reproducibility, reversibility and selectivity. The recommended method was successfully used for the determination of berberine in pharmaceutical preparations.


title: A G3P[13] porcine group A rotavirus emerging in China is a reassortant and a natural recombinant in the VP4 gene

text: Group A rotaviruses (RVAs) are a major cause of serious intestinal disease in piglets. In this study, a novel pig strain was identified in a stool sample from China. The strain was designated RVA/Pig/China/LNCY/2016/G3P[13] and had a G3‐P[13]‐I5‐R1‐C1‐M1‐A8‐N1‐T1‐E1‐H1 genome. The viral protein 7 (VP7) and non‐structural protein 4 (NSP4) genes of RVA/Pig/China/LNCY/2016/G3P[13] were closely related to cogent genes of human RVAs, suggesting that a reassortment between pig and human strains had occurred. Recombination analysis showed that RVA/Pig/China/LNCY/2016/G3P[13] is a natural recombinant strain between the P[23] and P[7] RVA strains, and crossover points for recombination were found at nucleotides (nt) 456 and 804 of the VP4 gene. Elucidating the biological characteristics of porcine rotavirus (PoRV) will be helpful for further analyses of the epidemic characteristics of this virus. The results of this study provide valuable information for RVA recombination and evolution and will facilitate future investigations into the molecular pathogenesis of RVAs.


title: Ebola Virus Disease Clinical Challenges, Recognition, and Management

text: The 2014 to 2016 Ebola outbreak response resulted in many lessons learned about biocontainment patient care, leading to enhanced domestic capabilities for highly infectious and hazardous communicable diseases. However, additional opportunities for improvement remain. The article identifies and describes key considerations and challenges for laboratory analysis, clinical management, transportation, and personnel management during the care of patients infected with Ebola or other special pathogens. Dedication to maintaining preparedness enables biocontainment patient care teams to perform at the highest levels of safety and confidence.


title: A feasibility study of conducting surveillance for swine pathogens in slurry from North Carolina swine farms

text: Despite close contact between humans and animals on large scale farms, little to no infectious disease research is conducted at this interface. Our goal in this preliminary study was to explore if we could detect swine pathogens using a non-invasive, indirect approach through the study of swine slurry. From April to November 2018, 105 swine slurry samples were collected by farm personnel from waste pits at two sites on a swine farm in North Carolina. These samples were tested for DNA and RNA viruses using a real-time PCR and RT-PCR. Statistical analyses were performed to measure association between virus positive outcomes and potential predictors such as date of sample collection, weight of pigs, number of pigs in barn, temperature, and weather conditions. Overall, 86% of the samples had evidence of at least one of the targeted viruses. Ultimately, this study demonstrated the utility of conducting noninvasive surveillance for swine pathogens through the study of swine slurry. Such swine slurry surveillance may supplant the need to handle, restrain, and collect specimens directly from pigs thus providing an approach to emerging pathogen detection that appeals to the swine industry.


title: Epidemiological characteristics of human-infective RNA viruses

text: RNA viruses are a major threat to human health. Here, based on extensive literature searches carried out over a period of 18 years, we provide a catalogue of all 214 known human-infective RNA virus species. We link these viruses to metadata for a number of traits that influence their epidemiology, including the date of the first report of human infection, transmissibility in human populations, transmission route(s) and host range. This database can be used in comparative studies of human-infective RNA viruses to identify the characteristics of viruses most likely to pose the greatest public health threat, both now and in the future.


title: Genetic Characteristics of Coronaviruses from Korean Bats in 2016

text: Bats have increasingly been recognized as the natural reservoir of severe acute respiratory syndrome (SARS), coronavirus, and other coronaviruses found in mammals. However, little research has been conducted on bat coronaviruses in South Korea. In this study, bat samples (332 oral swabs, 245 fecal samples, 38 urine samples, and 57 bat carcasses) were collected at 33 natural bat habitat sites in South Korea. RT-PCR and sequencing were performed for specific coronavirus genes to identify the bat coronaviruses in different bat samples. Coronaviruses were detected in 2.7% (18/672) of the samples: 13 oral swabs from one species of the family Rhinolophidae, and four fecal samples and one carcass (intestine) from three species of the family Vespertiliodae. To determine the genetic relationships of the 18 sequences obtained in this study and previously known coronaviruses, the nucleotide sequences of a 392-nt region of the RNA-dependent RNA polymerase (RdRp) gene were analyzed phylogenetically. Thirteen sequences belonging to SARS-like betacoronaviruses showed the highest nucleotide identity (97.1–99.7%) with Bat-CoV-JTMC15 reported in China. The other five sequences were most similar to MERS-like betacoronaviruses. Four nucleotide sequences displayed the highest identity (94.1–95.1%) with Bat-CoV-HKU5 from Hong Kong. The one sequence from a carcass showed the highest nucleotide identity (99%) with Bat-CoV-SC2013 from China. These results suggest that careful surveillance of coronaviruses from bats should be continued, because animal and human infections may result from the genetic variants present in bat coronavirus reservoirs.


The Income-Based Mortality Gradient Among US Health Care Workers: Cohort Study


How to cite this article: Vijayaraghavan BKT, Venkataraman R, Ramakrishnan N. Critical Care Epidemiology and Research in the Face of a Pandemic: An Opportunity in a Crisis. Indian J Crit Care Med 2020;24(4):242–244.


Evaluation of the Slit Lamp Shield to reduce droplet exposure


title: Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster

text: Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.


title: Age-specific and sex-specific morbidity and mortality from avian influenza A(H7N9)

text: Abstract We used data on age and sex for 136 laboratory confirmed human A(H7N9) cases reported as of 11 August 2013 to compare age-specific and sex-specific patterns of morbidity and mortality from the avian influenza A(H7N9) virus with those of the avian influenza A(H5N1) virus. Human A(H7N9) cases exhibit high degrees of age and sex bias: mortality is heavily biased toward males >50 years, no deaths have been reported among individuals <25 years old, and relatively few cases documented among children or adolescents. The proportion of fatal cases (PFC) for human A(H7N9) cases as of 11 August 2013 was 32%, compared to a cumulative PFC for A(H5N1) of 83% in Indonesia and 36% in Egypt. Approximately 75% of cases of all A(H7N9) cases occurred among individuals >45 years old. Morbidity and mortality from A(H7N9) are lowest among individuals between 10 and 29 years, the age group which exhibits the highest cumulative morbidity and case fatality rates from A(H5N1). Although individuals <20 years old comprise nearly 50% of all human A(H5N1) cases, only 7% of all reported A(H7N9) cases and no deaths have been reported among individuals in this age group. Only 4% of A(H7N9) cases occurred among children<5 years old, and only one case from the 10 to 20 year age group. Age- and sex-related differences in morbidity and mortality from emerging zoonotic diseases can provide insights into ecological, economic, and cultural factors that may contribute to the emergence and proliferation of novel zoonotic diseases in human populations.


A Google Trends study on the interest in self-medication during the 2019 novel Coronavirus (COVID-19) disease pandemic


title: A Heuristic Indication and Warning Staging Model for Detection and Assessment of Biological Events

text: OBJECTIVE: This paper presents a model designed to enable rapid detection and assessment of biological threats that may require swift intervention by the international public health community. DESIGN: We utilized Strauss’ grounded theory to develop an expanded model of social disruption due to biological events based on retrospective and prospective case studies. We then applied this model to the temporal domain and propose a heuristic staging model, the Wilson–Collmann Scale for assessing biological event evolution. MEASUREMENTS: We retrospectively and manually examined hard copy archival local media reports in the native vernacular for three biological events associated with substantial social disruption. The model was then tested prospectively through media harvesting based on keywords corresponding to the model parameters. RESULTS: Our heuristic staging model provides valuable information about the features of a biological event that can be used to determine the level of concern warranted, such as whether the pathogen in question is responding to established public health disease control measures, including the use of antimicrobials or vaccines; whether the public health and medical infrastructure of the country involved is adequate to mount the necessary response; whether the country’s officials are providing an appropriate level of information to international public health authorities; and whether the event poses a international threat. The approach is applicable for monitoring open-source (public-domain) media for indications and warnings of such events, and specifically for markers of the social disruption that commonly occur as these events unfold. These indications and warnings can then be used as the basis for staging the biological threat in the same manner that the United States National Weather Service currently uses storm warning models (such as the Saffir-Simpson Hurricane Scale) to detect and assess threatening weather conditions. CONCLUSION: Used as a complement to current epidemiological surveillance methods, our approach could aid global public health officials and national political leaders in responding to biological threats of international public health significance.


title: Current knowledge on the structural proteins of porcine reproductive and respiratory syndrome (PRRS) virus: comparison of the North American and European isolates

text: Porcine reproductive and respiratory syndrome virus (PRRSV) belongs to the recently recognized Arteriviridae family within the genus Arterivirus, order Nidovirales, which also includes equine arteritis virus (EAV), lactate dehydrogenase-elevating virus (LDV), and simian hemorrhagic fever virus (SHFV). Mature viral particles are composed of an envelope 50–72 nm in diameter, with an isometric core about 20–30 nm enclosing a linear positive-stranded RNA genome of approximately 15 kb. The virions are assembled by the budding of preformed nucleocapsids into the lumen of the smooth endoplasmic reticulum and/or Golgi apparatus. The mature virions are then released by exocytosis. The viral genome contains eight open reading frames (ORFs) which are transcribed in cells as a nested set of subgenomic mRNAs. The ORF1a and ORF1b situated at the 5′end of the genome represent nearly 75% of the viral genome and code for proteins with apparent replicase and polymerase activities. The major structural proteins consist of a 25 kDa envelope glycoprotein (GP(5)), an 18–19 kDa unglycosylated membrane protein (M), and a 15 kDa nucleocapsid (N) protein, encoded by ORFs 5, 6 and 7, respectively. The N protein is the more abundant protein of the virion and is highly antigenic, which therefore makes it a suitable candidate for the detection of virus-specific antibodies and diagnosis of the disease. Four to five domains of antigenic importance have been identified for the N protein, a common conformational antigenic site for European and North American strains being localized in the central region of the protein. In cells and virions, both M and GP(5) occur in heterodimeric complexes linked by disulfide bonds. The expression products of ORFs 2 and 4 are also incorporated into virus particles as additional minor membrane-associated glycoproteins designated as GP(2) and GP(4), with M(r) of 29 and 31 kDa, respectively. The structural nature of the ORF3 product, a highly glycosylated protein with an apparent M(r) of 42 kDa, is still being debated, in view of the apparently conflicting data on its presence in virus particles. Nonetheless, the GP(3) of North American and European strains has been shown to be antigenic, providing protection for piglets against PRRSV infection in the absence of a noticeable neutralizing humoral response. Pigs exposed to the native form of GP(5) by means of DNA immunization develop specific neutralizing and protecting antibodies. The GP(5) is involved in antigenic variability, apoptosis, and possibly antibody-dependent enhancement phenomena. The GP(4) also possesses antigenic determinants that trigger the immune system to produce neutralizing antibodies. Each of the PRRSV structural proteins carries common and type-specific antigenic determinants that permit the ability to differentiate between European and North American strains. The potential use of the PRRSV structural proteins in subunit recombinant-type vaccines is also discussed.


title: Research agenda for mass gatherings: a call to action

text: Summary Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.


“Thinking outside the box in COVID‐19 era”‐Application of Modified Aerosol Box in Dermatology


title: Outcomes of Hematopoietic Stem Cell Transplant Recipients with Rhinovirus Infection: A Matched, Case-Control Study

text: The impact of rhinovirus in hematopoietic stem cell transplant (HSCT) recipients is not well defined. A retrospective, matched, case-control study of HSCT recipients with rhinovirus was conducted between 2009 and 2011. Controls were matched for timing relative to transplant, malignancy, and stem cell source. There were 47 cases and 94 controls. Cases and controls did not differ with respect to age, gender, ethnicity, donor source, malignancy, conditioning regimen, immunosuppression, antimicrobial prophylaxis, or significant comorbidities. There were no differences in need for ICU care, 100 day mortality, hospice discharge, relapse of disease, GVHD or development of disease or infection due to CMV or EBV. Other infectious complications after rhinovirus diagnosis were also equal. However, there was an increased number of recurrent hospitalizations from any cause among cases (46.8% vs. 24.5%, P=0.007). Recurrent hospitalizations due to any infection were also more common in cases (34% vs. 14.9%, P=0.015). For patients who were diagnosed with rhinovirus pre-transplant (n=13), there was no difference in outcomes compared to matched controls. HSCT recipients with rhinovirus have an increased risk of hospital readmission. However, there was no difference in outcomes compared to matched controls. Transplantation in patients with active rhinovirus infection appears to be safe.


title: Influence of wind and relative humidity on the social distancing effectiveness to prevent COVID-19 airborne transmission: A numerical study

text: It has been confirmed that the coronavirus disease 2019 (COVID-19) can transmit through droplets created when an infected human coughs or sneezes. Accordingly, 1.83-m (6-feet) social distancing is advised to reduce the spread of the disease among humans. This is based on the assumption that no air circulation exists around people. However, it is not well investigated whether the ambient wind and relative humidity (RH) will cause SARS-CoV-2 laden droplets to transport farther in the air, making the current social distancing policy insufficient. To provide evidence and insight into the “social distancing” guidelines, a validated computational fluid-particle dynamics (CFPD) model was employed to simulate the transient transport, condensation/evaporation, and deposition of SARS-CoV-2 laden droplets emitted by coughs, with different environmental wind velocities and RHs. Initial droplet diameters range from 2 to 2000 μm, and the wind velocities range from 0 to 16 km/h, representing different wind forces from calm air to moderate breeze. The comparison between a steady-state wind and a gust with a constant frequency has also been performed. Ambient RHs are 40% and 99.5%. The distances between the two virtual humans are 1.83 m and 3.05 m (6 feet and 10 feet). The facial covering effect on reducing the airborne transmission of the cough droplets has also been evaluated. Numerical results indicate that the ambient wind will enhance the complexity of the secondary flows with recirculation between the two virtual humans. Microdroplets follow the airflow streamlines well and deposit on both human bodies and head regions, even with the 3.05-m (10-feet) separation distance. The rest of the microdroplets can transport in the air farther than 3.05 m (10 feet) due to wind convection, causing a potential health risk to nearby people. High RH will increase the droplet sizes due to the hygroscopic growth effect, which increases the deposition fractions on both humans and the ground. With the complex environmental wind and RH conditions, the 6-feet social distancing policy may not be sufficient to protect the inter-person aerosol transmission, since the suspending micro-droplets were influenced by convection effects and can be transported from the human coughs/sneezes to the other human in less than 5 s. Thus, due to the complex real-world environmental ventilation conditions, a social distance longer than 6 feet needs to be considered. Wearing masks should also be recommended for both infected and healthy humans to reduce the airborne cough droplet numbers.


title: Mammalian phosphatidylinositol 4-kinases as modulators of membrane trafficking and lipid signaling networks

text: Abstract The four mammalian phosphatidylinositol 4-kinases modulate inter-organelle lipid trafficking, phosphoinositide signalling and intracellular vesicle trafficking. In addition to catalytic domains required for the synthesis of PI4P, the phosphatidylinositol 4-kinases also contain isoform-specific structural motifs that mediate interactions with proteins such as AP-3 and the E3 ubiquitin ligase Itch, and such structural differences determine isoform-specific roles in membrane trafficking. Moreover, different permutations of phosphatidylinositol 4-kinase isozymes may be required for a single cellular function such as occurs during distinct stages of GPCR signalling and in Golgi to lysosome trafficking. Phosphatidylinositol 4-kinases have recently been implicated in human disease. Emerging paradigms include increased phosphatidylinositol 4-kinase expression in some cancers, impaired functioning associated with neurological pathologies, the subversion of PI4P trafficking functions in bacterial infection and the activation of lipid kinase activity in viral disease. We discuss how the diverse and sometimes overlapping functions of the phosphatidylinositol 4-kinases present challenges for the design of isoform-specific inhibitors in a therapeutic context.


title: Recombinant M protein-based ELISA test for detection of antibodies to canine coronavirus

text: Abstract The membrane (M) protein of canine coronavirus (CCoV) was cloned and expressed in E. coli. The purified recombinant protein was then evaluated for its antigenicity and reliability in an enzyme-linked immunosorbent assay (ELISA) for detection of CCoV antibodies in dog sera. Fifty serum samples, screened previously by whole virus ELISA and Western blotting, were tested. When the performance of the new test was compared with those of whole virus ELISA and Western blotting, an excellent correlation was found with the latter two assays. The ELISA based on recombinant M protein represents an alternative and valid test for detection of antibodies to CCoV in dog sera.


title: COVID-19 and the 5G Conspiracy Theory: Social Network Analysis of Twitter Data

text: BACKGROUND: Since the beginning of December 2019, the coronavirus disease (COVID-19) has spread rapidly around the world, which has led to increased discussions across online platforms. These conversations have also included various conspiracies shared by social media users. Amongst them, a popular theory has linked 5G to the spread of COVID-19, leading to misinformation and the burning of 5G towers in the United Kingdom. The understanding of the drivers of fake news and quick policies oriented to isolate and rebate misinformation are keys to combating it. OBJECTIVE: The aim of this study is to develop an understanding of the drivers of the 5G COVID-19 conspiracy theory and strategies to deal with such misinformation. METHODS: This paper performs a social network analysis and content analysis of Twitter data from a 7-day period (Friday, March 27, 2020, to Saturday, April 4, 2020) in which the #5GCoronavirus hashtag was trending on Twitter in the United Kingdom. Influential users were analyzed through social network graph clusters. The size of the nodes were ranked by their betweenness centrality score, and the graph’s vertices were grouped by cluster using the Clauset-Newman-Moore algorithm. The topics and web sources used were also examined. RESULTS: Social network analysis identified that the two largest network structures consisted of an isolates group and a broadcast group. The analysis also revealed that there was a lack of an authority figure who was actively combating such misinformation. Content analysis revealed that, of 233 sample tweets, 34.8% (n=81) contained views that 5G and COVID-19 were linked, 32.2% (n=75) denounced the conspiracy theory, and 33.0% (n=77) were general tweets not expressing any personal views or opinions. Thus, 65.2% (n=152) of tweets derived from nonconspiracy theory supporters, which suggests that, although the topic attracted high volume, only a handful of users genuinely believed the conspiracy. This paper also shows that fake news websites were the most popular web source shared by users; although, YouTube videos were also shared. The study also identified an account whose sole aim was to spread the conspiracy theory on Twitter. CONCLUSIONS: The combination of quick and targeted interventions oriented to delegitimize the sources of fake information is key to reducing their impact. Those users voicing their views against the conspiracy theory, link baiting, or sharing humorous tweets inadvertently raised the profile of the topic, suggesting that policymakers should insist in the efforts of isolating opinions that are based on fake news. Many social media platforms provide users with the ability to report inappropriate content, which should be used. This study is the first to analyze the 5G conspiracy theory in the context of COVID-19 on Twitter offering practical guidance to health authorities in how, in the context of a pandemic, rumors may be combated in the future.