title: IFN-γ–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations

text: Background Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations. Objective We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma. Methods BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments. Results IFN-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r = −0.8; P < .01). Conclusions IP-10 release is specific to acute virus-induced asthma. Clinical implications Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.


title: BAG3: a multifaceted protein that regulates major cell pathways

text: Bcl2-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that interacts with the ATPase domain of the heat shock protein (Hsp) 70 through BAG domain (110–124 amino acids). BAG3 is the only member of the family to be induced by stressful stimuli, mainly through the activity of heat shock factor 1 on bag3 gene promoter. In addition to the BAG domain, BAG3 contains also a WW domain and a proline-rich (PXXP) repeat, that mediate binding to partners different from Hsp70. These multifaceted interactions underlie BAG3 ability to modulate major biological processes, that is, apoptosis, development, cytoskeleton organization and autophagy, thereby mediating cell adaptive responses to stressful stimuli. In normal cells, BAG3 is constitutively present in a very few cell types, including cardiomyocytes and skeletal muscle cells, in which the protein appears to contribute to cell resistance to mechanical stress. A growing body of evidence indicate that BAG3 is instead expressed in several tumor types. In different tumor contexts, BAG3 protein was reported to sustain cell survival, resistance to therapy, and/or motility and metastatization. In some tumor types, down-modulation of BAG3 levels was shown, as a proof-of-principle, to inhibit neoplastic cell growth in animal models. This review attempts to outline the emerging mechanisms that can underlie some of the biological activities of the protein, focusing on implications in tumor progression.


Pandemic Fear and Literature: Observations from Jack London’s The Scarlet Plague


title: Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

text: New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI 0.73–1.0), specificity of 0.66 (95% CI 0.52–0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75–0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47–0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.


title: Epidemiology

text: Abstract Although lacking the control available to toxicity studies, epidemiology allows for much larger study sizes and is particularly useful for identifying causal factors for population-wide health concerns. Some epidemiological studies are given more credence than their toxicological counterparts because the data are seen as more accurate for ‘real-life’ situations. Also, data collected for completely different reasons can often be incorporated into an epidemiological study. The greatest difference between epidemiology and toxicology, aside from the observational/experimental basis, is the measure of exposure, which, although it would improve any study, is often difficult to incorporate into epidemiological studies because of the historical nature of exposures.


title: Bat Caliciviruses and Human Noroviruses Are Antigenically Similar and Have Overlapping Histo-Blood Group Antigen Binding Profiles

text: Emerging zoonotic viral diseases remain a challenge to global public health. Recent surveillance studies have implicated bats as potential reservoirs for a number of viral pathogens, including coronaviruses and Ebola viruses. Caliciviridae represent a major viral family contributing to emerging diseases in both human and animal populations and have been recently identified in bats. In this study, we blended metagenomics, phylogenetics, homology modeling, and in vitro assays to characterize two novel bat calicivirus (BtCalV) capsid sequences, corresponding to strain BtCalV/A10/USA/2009, identified in Perimyotis subflavus near Little Orleans, MD, and bat norovirus. We observed that bat norovirus formed virus-like particles and had epitopes and receptor-binding patterns similar to those of human noroviruses. To determine whether these observations stretch across multiple bat caliciviruses, we characterized a novel bat calicivirus, BtCalV/A10/USA/2009. Phylogenetic analysis revealed that BtCalV/A10/USA/2009 likely represents a novel Caliciviridae genus and is most closely related to "recoviruses." Homology modeling revealed that the capsid sequences of BtCalV/A10/USA/2009 and bat norovirus resembled human norovirus capsid sequences and retained host ligand binding within the receptor-binding domains similar to that seen with human noroviruses. Both caliciviruses bound histo-blood group antigens in patterns that overlapped those seen with human and animal noroviruses. Taken together, our results indicate the potential for bat caliciviruses to bind histo-blood group antigens and overcome a significant barrier to cross-species transmission. Additionally, we have shown that bat norovirus maintains antigenic epitopes similar to those seen with human noroviruses, providing further evidence of evolutionary descent. Our results reiterate the importance of surveillance of wild-animal populations, especially of bats, for novel viral pathogens.


title: Generation of MERS-CoV Pseudotyped Viral Particles for the Evaluation of Neutralizing Antibodies in Mammalian Sera

text: Pseudotyped viral particle production has been used extensively and broadly for many viruses to evaluate levels of neutralizing antibodies, viral entry inhibitors and vaccine immunogenicity. This assay is extremely safe and useful alternative to live virus-based assay without the need for high containment facilities. In this chapter, we describe the generation of MERS-CoV pseudotyped viral particles (MERSpp) expressing full-length spike protein using second-generation lentiviral packaging system. This platform is optimized to generate high titer of MERSpp and to test sera from different mammalian species.


title: Economic review

text: Abstract Severe Acute Respiratory Syndrome (SARS) has taken its toll on Japanese companies operating in East Asia, according to a Japan External Trade Organization (JETRO) survey conducted in June.


title: Impact of weather on COVID-19 pandemic in Turkey

text: Abstract The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (°C), dew point (°C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.


title: Probing the structural dynamics of proteins and nucleic acids with optical tweezers

text: Conformational changes are an essential feature of most molecular processes in biology. Optical tweezers have emerged as a powerful tool for probing conformational dynamics at the single-molecule level because of their high resolution and sensitivity, opening new windows on phenomena ranging from folding and ligand binding to enzyme function, molecular machines, and protein aggregation. By measuring conformational changes induced in a molecule by forces applied by optical tweezers, new insight has been gained into the relationship between dynamics and function. We discuss recent advances from studies of how structure forms in proteins and RNA, including non-native structures, fluctuations in disordered proteins, and interactions with chaperones assisting native folding. We also review the development of assays probing the dynamics of complex protein–nucleic acid and protein–protein assemblies that reveal the dynamic interactions between biomolecular machines and their substrates.


title: Incidence and risk factors of lower respiratory tract illnesses during infancy in a Mediterranean birth cohort

text: Aim: To investigate the incidence rate, viral respiratory agents and determinants of lower respiratory tract illnesses (LRTIs) in infants younger than 1 year. Methods: A total of 487 infants were recruited at birth for the Asthma Multicenter Infant Cohort Study in Barcelona (Spain). Cases of LRTIs were ascertained through an active register including a home visit and viral test in nasal lavage specimens during the first year of life. Cotinine in cord blood, household aeroallergens, indoor NO(2) and maternal and neonatal IgE were measured. Other maternal and infants' characteristics were obtained from structured questionnaires. Results: The incidence rate of at least one LRTI was 38.7 infants per 100 persons‐years. The most frequently isolated viral agent was respiratory syncytial virus (44.7%). The risk of LRTIs was higher in infants with a maternal history of asthma and in those with siblings (OR = 2.4; 95% CI: 0.98–6.08 and OR = 1.8; 95% CI: 1.04–3.21, respectively). The risk of LRTIs was lower in infants who were breast fed for more than 12 weeks (OR = 0.26; 95% CI: 0.26–0.86) and in those from a low socioeconomic class (OR = 0.16; 95% CI: 0.06–0.42). Conclusion: Viral LRTIs are frequent in infants younger than 1 year of age and there is an inter‐relationship between maternal asthma, siblings, breast feeding and socioeconomic status.


title: Crystal structure of the papain-like protease of MERS coronavirus reveals unusual, potentially druggable active-site features

text: Abstract The Middle-East Respiratory Syndrome coronavirus (MERS-CoV) causes severe acute pneumonia and renal failure. The MERS-CoV papain-like protease (PLpro) is a potential target for the development of antiviral drugs. To facilitate these efforts, we determined the three-dimensional structure of the enzyme by X-ray crystallography. The molecule consists of a ubiquitin-like domain and a catalytic core domain. The catalytic domain displays an extended right-hand fold with a zinc ribbon and embraces a solvent-exposed substrate-binding region. The overall structure of the MERS-CoV PLpro is similar to that of the corresponding SARS-CoV enzyme, but the architecture of the oxyanion hole and of the S3 as well as the S5 specificity sites differ from the latter. These differences are the likely reason for reduced in vitro peptide hydrolysis and deubiquitinating activities of the MERS-CoV PLpro, compared to the homologous enzyme from the SARS coronavirus. Introduction of a side-chain capable of oxyanion stabilization through the Leu106Trp mutation greatly enhances the in vitro catalytic activity of the MERS-CoV PLpro. The unique features observed in the crystal structure of the MERS-CoV PLpro should allow the design of antivirals that would not interfere with host ubiquitin-specific proteases.


title: A Mini-Review on the Epidemiology of Canine Parvovirus in China

text: Canine viral diarrhea is a severe disease in dogs worldwide. The role of canine parvovirus (CPV) in canine viral diarrhea is a common health problem in dogs, attracting major concern from veterinarians and dog owners across China. In this mini-review, we summarize the CPV epidemiology in China, including its origin, prevalence, coinfection, and the genetic evolution of the virus. The review reveals the correlation between CPV-2 infection and seasonality, a dog's age/gender/breed/vaccination; that CPV-2 is the main causative agent of canine diarrhea in Northeast China and that coinfection with other pathogens is a common occurrence; the predominant CPV epidemic strains were the new CPV-2a, and CPV-2c has shown significant growth trends since 2010. This mini-review will provide valuable information for CPV infections across China and other countries.


title: Novel Orthopoxvirus and Lethal Disease in Cat, Italy

text: We report detection and full-genome characterization of a novel orthopoxvirus (OPXV) responsible for a fatal infection in a cat. The virus induced skin lesions histologically characterized by leukocyte infiltration and eosinophilic cytoplasmic inclusions. Different PCR approaches were unable to assign the virus to a defined OPXV species. Large amounts of typical brick-shaped virions, morphologically related to OPXV, were observed by electron microscopy. This OPXV strain (Italy_09/17) was isolated on cell cultures and embryonated eggs. Phylogenetic analysis of 9 concatenated genes showed that this virus was distantly related to cowpox virus, more closely related to to ectromelia virus, and belonged to the same cluster of an OPXV recently isolated from captive macaques in Italy. Extensive epidemiologic surveillance in cats and rodents will assess whether cats are incidental hosts and rodents are the main reservoir of the virus. The zoonotic potential of this novel virus also deserves further investigation.


title: A changing world, again. How Appreciative Inquiry can guide our growth

text: Abstract COVID-19 is an interconnecting, cascading tsunami of up-rootedness and change on many levels. The global challenge we face is twofold: 1) how do we sustain our psychological, physical, social and economic capital and wellbeing in a time of great uncertainty; and 2) how do we adapt and create a new existence in an altered reality? Appreciative Inquiry (AI) is a well-documented approach to helping individuals and systems move from a deficit-based paradigm to a strengths-based perspective. AI holds myriad potential benefits for individuals, communities, and macro systems to build resilience and promote growth during and after COVID-19. This article will provide an overview of AI and its relevance to the current situation, as well as provide specific strategies for how people and systems can use AI as they transition through the pandemic and afterward.


title: Relative frequency, Possible Risk Factors, Viral Codetection Rates, and Seasonality of Respiratory Syncytial Virus Among Children With Lower Respiratory Tract Infection in Northeastern Brazil

text: Few studies, each limited to a single major city, have investigated the prevalence and seasonal patterns of different viruses among children with low respiratory tract infections (LRTI) in Northeastern Brazil. The aim of this study was to determine the frequency of respiratory syncytial virus (RSV) and of 7 other viruses in children for LRTI in 4 capitals from this region, and investigate their association with several risk factors, including meteorological data. From April 2012 to March 2013, 507 children, aged up to 24 months and hospitalized with LRTI in one of the participating centers at Aracajú, Salvador, Recife, and Maceió, had a sample of nasopharyngeal aspirate collected and analyzed for the following viruses by reverse-transcription polymerase chain reaction followed by hybridization on low-density microarrays: RSV, influenza, parainfluenza, adenovirus, rhinovirus, metapneumovirus, bocavirus, and coronavirus. The result was positive in 66.5% of cases, RSV was the most common virus (40.2%). Except for rhinovirus (17%), all other virus had frequency rates lower than 6%. Viral coinfections were detected in 13.8% of samples. Possible related risk factors for RSV infection were low age upon entry, attendance of daycare, low gestational age, and low educational level of the father. The relative frequency of viral infections was associated with increasing temperature and decreasing humidity separately, but the results also suggested both associated with increased frequency of RSV. Some of these findings differ from those reported for other regions in Brazil and may be used to guide policies that address LRTI.


title: An assessment of Ebola-related stigma and its association with informal healthcare utilisation among Ebola survivors in Sierra Leone: a cross-sectional study

text: BACKGROUND: We examined the magnitude and correlates of Ebola virus disease (EVD)-related stigma among EVD survivors in Sierra Leone since their return to their communities. In addition, we determined whether EVD-related stigma is a predictor of informal health care use among EVD survivors. METHODS: We conducted a cross-sectional study among 358 EVD survivors in five districts across all four geographic regions (Western Area, Northern Province, Eastern Province and Southern Province) of Sierra Leone. Ebola-related stigma was measured by adapting the validated HIV related stigma for people living with HIV/AIDS instrument. We also measured traditional and complementary medicine (T&CM) use (as a measure of informal healthcare use). Data were analysed using descriptive statistics and regression analysis. RESULTS: EVD survivors report higher levels of internalised stigma (0.92 ± 0.77) compared to total enacted stigma (0.71 ± 0.61). Social isolation (0.96 ± 0.88) was the highest reported enacted stigma subscale. Ebola survivors who identified as Christians [AOR = 2.51, 95%CI: 1.15–5.49, p = 0.021], who perceived their health to be fair/poor [AOR = 2.58, 95%CI: 1.39–4.77. p = 0.003] and who reside in the northern region of Sierra Leone [AOR = 2.80, 95%CI: 1.29–6.07, p = 0.009] were more likely to experience internalised stigma. Verbal abuse [AOR = 1.95, 95%CI: 1.09–3.49, p = 0.025] and healthcare neglect [AOR = 2.35, 95%CI: 1.37–4.02, p = 0.002] were independent predictors of T&CM use among EVD survivors. CONCLUSION: Our findings suggest EVD-related stigma (internalised and enacted) is prevalent among EVD survivors since their return to their communities. Religiosity, perceived health status and region were identified as independent predictors of internalised stigma. Verbal abuse and healthcare neglect predict informal healthcare use. EVD survivor-centred and community-driven anti-stigma programs are needed to promote EVD survivors’ recovery and community re-integration.


title: Electronic data interchange usage in China's healthcare organizations: the case of Beijing's hospitals

text: China has long since realized the potential benefits of adopting electronic data exchange. In particular, the Chinese government is promoting the usage of electronic data interchange (EDI) in healthcare organizations. However, little research has described the current status of EDI usage in these organizations. This study investigates the extent of EDI usage in Beijing's hospitals along four dimensions: volume, diversity, breadth, and depth. The results from 57 hospitals show that EDI usage is in its very early stages. The study provides possible reasons for the low EDI usage from cultural, economic, and technological perspectives, analyzes the differences of EDI usage in the different levels of China's hospitals, and suggests strategies to promote EDI usage in China's healthcare organizations.


Coronavirus uses as binding site in humans angiotensin‐converting enzyme 2 functional receptor that is involved in arterial blood pressure control and fibrotic response to damage and is a drug target in cardiovascular disease. Is this just a phylogenetic coincidence?


title: Comment on ‘Two cases of COVID‐19 presenting with a clinical picture resembling chilblains: first report from the Middle East’: pernio unrelated to COVID‐19

text: Dear editor, we have read with interest Dr´s Alramthan and Aldaraji contribution to the spectrum of COVID-19 clinical manifestations.1 Since COVID-19 outbreak begin, new symptoms have been described.2 Some of them, were not initially highlighted and could be a distinguishing feature of COVID-19 infection, like anosmia or ageusia.3 Therefore, it is believed that a newly reported one, so-called acute acro-ischemia is another novel clinical manifestation of COVID-19 infection.4.


Human parechovirus: sepsis-like illness with pulmonary infection


title: The Domestic Ferret (Mustela putorius furo) as a Lethal Infection Model for 3 Species of Ebolavirus

text: Small-animal models have been developed for several Filoviridae species; however, serial adaptation was required to produce lethal infection. These adapted viruses have sequence changes in several genes, including those that modulate the host immune response. Nonhuman primate models do not require adaptation of filoviruses. Here, we describe lethal models of disease for Bundibugyo, Sudan, and Zaire species of Ebolavirus in the domestic ferret, using wild-type nonadapted viruses. Pathologic features were consistent with disease in primates. Of particular importance, this is the only known small-animal model developed for Bundibugyo and the only uniformly lethal animal model for Bundibugyo.


Author’s Reply: Hazardous Postoperative Outcomes of Unexpected COVID-19 Infected Patients: A Call for Global Consideration of Sampling All Asymptomatic Patients Before Surgical Treatment


title: Insights for increased risk of failed fibrinolytic therapy and stent thrombosis associated with COVID‐19 in ST‐segment elevation myocardial infarction patients

text: Important health resources are dedicated worldwide to the management of COVID‐19. This new disease, due to its large diffusion, may significantly hamper the prognosis of other pathologies, such as ST‐segment elevation myocardial infarction (STEMI) because of (a) a possible direct negative impact and (b) shortage of first response medical resources and increased delays to reperfusion. We report the case of a 68‐year‐old man admitted for anterior STEMI and asymptomatic COVID‐19. Due to extended transportation delays to a cathlab, he received intravenous fibrinolytic therapy, which failed. Reperfusion was achieved with rescue coronary angioplasty, but the patient experienced two episodes of acute stent thrombosis at 2‐ and 36‐hr following admission and despite optimal medical therapy. He finally died because of cardiogenic shock. This raises concerns about a possible increase in platelet aggregability associated with COVID‐19 leading to an increased risk of stent thrombosis, particularly in the context of STEMI. This pleads for the promotion of primary coronary angioplasty as the first‐choice revascularization technique in this population and the use of new generation P2Y12 inhibitors. In addition, the use of GPIIb/IIIa inhibitors may be considered in every STEMI patient with COVID‐19 to prevent the risk of acute stent thrombosis.


Multidrug resistant infections in the COVID-19 era, a framework for considering the potential impact


title: Antigenic characterization of severe acute respiratory syndrome-coronavirus nucleocapsid protein expressed in insect cells: The effect of phosphorylation on immunoreactivity and specificity

text: Abstract The nucleocapsid (N) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) is involved in the pathological reaction to SARS and is a key antigen for the development of a sensitive diagnostic assay. However, the antigenic properties of this N protein are largely unknown. To facilitate the studies on the function and antigenicity of the SARS-CoV N protein, 6× histidine-tagged recombinant SARS-CoV N (rSARS-N) with a molecular mass of 46 and 48kDa was successfully produced using the recombinant baculovirus system in insect cells. The rSARS-N expressed in insect cells (BrSARS-N) showed remarkably higher specificity and immunoreactivity than rSARS-N expressed in E. coli (ErSARS-N). Most of all, BrSARS-N proteins were expressed as a highly phosphorylated form with a molecular mass of 48kDa, but ErSARS-N was a nonphosphorylated protein. In further analysis to determine the correlation between the phosphorylation and the antigenicity of SARS-N protein, dephosphorylated SARS-N protein treated with protein phosphatase 1 (PP1) remarkably enhanced the cross-reactivity against SARS negative serum and considerably reduced immunoreactivity with SARS-N mAb. These results suggest that the phosphorylation plays an important role in the immunoreactivity and specificity of SARS-N protein. Therefore, the BrSARS-N protein may be useful for the development of highly sensitive and specific assays to determine SARS infection and for further research of SARS-N pathology.


title: Efficient spread-size approximation of opinion spreading in general social networks

text: In contemporary society, understanding how information, such as trends and viruses, spreads in various social networks is an important topic in many areas. However, it is difficult to mathematically measure how widespread the information is, especially for a general network structure. There have been studies on opinion spreading, but many studies are limited to specific spreading models such as the susceptible-infected-recovered model and the independent cascade model, and it is difficult to apply these studies to various situations. In this paper, we first suggest a general opinion spreading model (GOSM) that generalizes a large class of popular spreading models. In this model, each node has one of several states, and the state changes through interaction with neighboring nodes at discrete time intervals. Next, we show that many GOSMs have a stable property that is a GOSM version of a uniform equicontinuity. Then, we provide an approximation method to approximate the expected spread size for stable GOSMs. For the approximation method, we propose a concentration theorem that guarantees that a generalized mean-field theorem calculates the expected spreading size within small error bounds for finite time steps for a slightly dense network structure. Furthermore, we prove that a “single simulation” of running the Monte Carlo simulation is sufficient to approximate the expected spreading size. We conduct experiments on both synthetic and real-world networks and show that our generalized approximation method well predicts the state density of the various models, especially in graphs with a large number of nodes. Experimental results show that the generalized mean-field approximation and a single Monte Carlo simulation converge as shown in the concentration theorem.


title: Severe acute respiratory syndrome—a global concern—influenza virus isolated from suspected cases in Brazil from April to June 2003

text: Abstract Severe acute respiratory syndrome (SARS) is a condition associated with substantial morbidity and mortality. Coronavirus has been associated with this severe emerging disease, with a pattern suggesting droplet or contact transmission. From April to June 2003, Institute Adolfo Lutz received 16 respiratory secretions from hospitalized patients with recent history of travel to an area with local transmission of SARS. Rapid antigen detection for influenza A and B, parainfluenza types 1, 2 and 3, respiratory syncytial virus and adenovirus; electron microscopy, polymerase chain reaction (PCR), reverse transcription PCR (RT–PCR) and serologic assay were performed. Virus isolation attempts were performed in Hep-2, Vero, MDCK, NCI-H292, MRC-5, LLC-MK2 and FRhK-4. Influenza virus of type A/Panama/2007/99 (H3N2) and A/New Caledonia/20/99 (H1N2) were identified.


title: Role of bronchoalveolar lavage in the diagnosis of acute exacerbations of idiopathic pulmonary fibrosis: a retrospective study

text: BACKGROUND: It has been recognized that despite previous stability some patients with idiopathic pulmonary fibrosis (IPF) experience acute clinical deteriorations called acute exacerbations of idiopathic pulmonary fibrosis (AEX-IPF). We hypothesized that pulmonary infection can be excluded based on clinical and laboratory data and that bronchoscopy with BAL is not mandatory in the diagnostic work-up of suspected AEX-IPF. METHODS: In this retrospective study we identified patients with acute respiratory failure who were evaluated for AEX-IPF at the Cleveland Clinic between January 2002 and December 2011. Univariate and multivariate analysis were performed with predefined risk factors and final diagnosis of AEX-IPF and pulmonary infection. All tests were performed at a significance level of 0.05. RESULTS: A total of 77 patients met the study inclusion criteria. Of these patients 47 (61 %) were diagnosed with AEX-IPF. Bronchoscopy was more likely to be performed in patients who were on cytotoxic medications (p < 0.05). In most cases the diagnosis of AEX-IPF versus pulmonary infection was based on combination of other microbiological, clinical, radiologic data and clinical judgment. A total of 10 patients out of 14 (71 %) with a final diagnosis of pulmonary infection were on steroids on admission versus 21 out of 63 patients (33 %) with other final diagnosis (p = 0.024, OR 7.817, 95 % CI 1.31–46.64). CONCLUSIONS: Exclusion of infection in our IPF patient cohort was mostly based on factors other than diagnostic bronchoscopy with BAL. Based on our results we suggested an algorithm for management of IPF patients presenting with acute respiratory failure.


Microarray-based molecular detection of viral pathogens associated with respiratory infections


title: Global trends in emerging infectious diseases

text: Emerging infectious diseases (EIDs) are a significant burden on global economies and public health(1–3). Their emergence is thought to be driven largely by socio-economic, environmental and ecological factors(1–9), but no comparative study has explicitly analysed these linkages to understand global temporal and spatial patterns of EIDs. Here we analyse a database of 335 EID ‘events’ (origins of EIDs) between 1940 and 2004, and demonstrate non-random global patterns. EID events have risen significantly over time after controlling for reporting bias, with their peak incidence (in the 1980s) concomitant with the HIV pandemic. EID events are dominated by zoonoses (60.3% of EIDs): the majority of these (71.8%) originate in wildlife (for example, severe acute respiratory virus, Ebola virus), and are increasing significantly over time. We find that 54.3% of EID events are caused by bacteria or rickettsia, reflecting a large number of drug-resistant microbes in our database. Our results confirm that EID origins are significantly correlated with socio-economic, environmental and ecological factors, and provide a basis for identifying regions where new EIDs are most likely to originate (emerging disease ‘hotspots’). They also reveal a substantial risk of wildlife zoonotic and vector-borne EIDs originating at lower latitudes where reporting effort is low. We conclude that global resources to counter disease emergence are poorly allocated, with the majority of the scientific and surveillance effort focused on countries from where the next important EID is least likely to originate.


Skin Reactions of N95 masks and Medial Masks among Health Care Personnel: A self‐report questionnaire survey in China


Infección por SARS-CoV-2 asociada a diplopía y anticuerpos antirreceptor de acetilcolina


In world of epidemics, WHO's in control


title: “Filoviruses”: a real pandemic threat?

text: Filoviruses are zoonotic and among the deadliest viruses known to mankind, with mortality rates in outbreaks reaching up to 90%. Despite numerous efforts to identify the host reservoir(s), the transmission cycle of filoviruses between the animal host(s) and humans remains unclear. The last decade has witnessed an increase in filovirus outbreaks with a changing epidemiology. The high mortality rates and lack of effective antiviral drugs or preventive vaccines has propagated the fear that filoviruses may become a real pandemic threat. This article discusses the factors that could influence the possible pandemic potential of filoviruses and elaborates on the prerequisites for the containment of future outbreaks, which would help prevent the evolution of filovirus into more virulent and more transmissible viruses.


title: Rapid Design and Implementation of an Integrated Patient Self-Triage and Self-Scheduling Tool for COVID-19

text: OBJECTIVE: To rapidly deploy a digital patient-facing self-triage and self-scheduling tool in a large academic health system to address the COVID-19 pandemic. MATERIALS AND METHODS: We created a patient portal-based COVID-19 self-triage and self-scheduling tool and made it available to all primary care patients at this large academic health system. Asymptomatic patients were asked about exposure history and were then provided relevant information. Symptomatic patients were triaged into one of four categories—emergent, urgent, non-urgent or self-care— and then connected with the appropriate level of care via direct scheduling or telephone hotline. RESULTS: This self-triage and self-scheduling tool was designed and implemented in under two weeks. During the first 16 days of use, it was completed 1129 times by 950 unique patients. Of completed sessions, 315 (28%) were by asymptomatic patients, and 814 (72%) were by symptomatic patients. Symptomatic patient triage dispositions were as follows: 193 emergent (24%), 193 urgent (24%), 99 nonurgent (12%), 329 self-care (40%). Sensitivity for detecting emergency-level care was 87.5% (95% CI 61.7-98.5%). DISCUSSION: This self-triage and self-scheduling tool has been widely used by patients and is being rapidly expanded to other populations and health systems. The tool has recommended emergency-level care with high sensitivity, and decreased triage time for patients with less severe illness. The data suggests it also prevents unnecessary triage messages, phone calls and in-person visits. CONCLUSION: Patient self-triage tools integrated into electronic health record systems have the potential to greatly improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic.


title: Clinical and imaging features of COVID-19

text: Abstract Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.


title: Molecular characterization of adenoviral infections in Cuba: report of an unusual association of species D adenoviruses with different clinical syndromes

text: Adenoviruses are common pathogens that are responsible for a wide variety of infectious syndromes. The objectives of this study were to identify and characterize members of different adenovirus species at the molecular level and to describe the correlation between viruses and clinical syndromes during a period of 4 years. Between 2002 and 2006, 45 of 512 respiratory specimens (8%) from patients with acute respiratory tract infection tested positive for adenovirus. Four adenovirus isolates from samples sent for enterovirus isolation were also analyzed. This research identified 49 confirmed cases of human adenovirus infection by PCR and/or viral culture. The most common diagnosis was upper respiratory infection (44%). Human adenovirus D was the major species found (59%), followed by Human adenovirus C (36%) and Human adenovirus B (4%). Human adenovirus 5 was the major serotype found producing bronchiolitis, followed by human adenovirus 6. In patients with upper respiratory infection, the major serotype found was human adenovirus 17. Viruses of the species Human adenovirus D were identified in seven (77%) cases of acute febrile syndrome. Four isolates from clinical materials obtained from patients with encephalitis, acute flaccid paralysis and meningoencephalitis were identified as belonging to the species Human adenovirus D. Our data demonstrate a surprising result about the identification of an unusual association of viruses of the species Human adenovirus D with different clinical syndromes. This observation could be evaluated as a possible indicator of the emergence of a novel strain but further studies are required.


title: Characterization of a novel Mycoplasma cynos real-time PCR assay

text: Mycoplasma cynos is recognized as an emerging causative pathogen of canine infectious respiratory disease (CIRD) worldwide. We developed a new open-source real-time PCR (rtPCR) assay for M. cynos that performs well under standard rtPCR conditions. Primers and probes were designed to target the M. cynos tuf gene. Reaction efficiencies for the M. cynos tuf gene assay on 2 platforms were based on amplification of standard curves spanning 8 orders of magnitude: ABI 7500 platform, 94.3–97.9% (r(2) ≥ 0.9935); QuantStudio OpenArray platform, 119.1–122.5% (r(2) = 0.9784). The assay performed very well over a range of template input, from 10(9) copies to the lower limit of quantification at 4 copies of the M. cynos genome on the ABI 7500 platform. Diagnostic performance was estimated by comparison with an in-house legacy assay on clinical specimens as well as testing isolates that were characterized previously by intergenic spacer region (ISR) sequencing. Exclusivity was established by testing 12 other Mycoplasma species. To substantiate the high specificity of the M. cynos tuf gene assay, sequence confirmation was performed on ISR PCR amplicons obtained from clinical specimens. One ISR amplicon sequence revealed M. mucosicanis rather than M. cynos. The complete protocol of the newly developed M. cynos tuf assay is provided to facilitate assay harmonization.


title: A multivariate threshold stochastic volatility model

text: Abstract We introduce in this paper a multivariate threshold stochastic volatility model for multiple financial return time series. This model allows the dynamic structure of return and volatility to change according to a threshold model while accounting for the interdependence of financial returns. Through the threshold volatility modeling, we can understand the impact of market news on volatility asymmetry. Estimation of unknown parameters are carried out using Markov chain Monte Carlo techniques. Simulations show that our estimators are reliable in moderately large sample sizes. We apply the model to three market indice data and estimate time-varying correlations among the indice returns.


We are now planning for our recovery phase, while continuing to provide the safest care possible for our patients


title: Deterministic analysis of extrinsic and intrinsic noise in an epidemiological model

text: We couple a stochastic collocation method with an analytical expansion of the canonical epidemiological master equation to analyze the effects of both extrinsic and intrinsic noise. It is shown that depending on the distribution of the extrinsic noise, the master equation yields quantitatively different results compared to using the expectation of the distribution for the stochastic parameter. This difference is incident to the nonlinear terms in the master equation, and we show that the deviation away from the expectation of the extrinsic noise scales nonlinearly with the variance of the distribution. The method presented here converges linearly with respect to the number of particles in the system and exponentially with respect to the order of the polynomials used in the stochastic collocation calculation. This makes the method presented here more accurate than standard Monte Carlo methods, which suffer from slow, nonmonotonic convergence. In epidemiological terms, the results show that extrinsic fluctuations should be taken into account since they effect the speed of disease breakouts and that the gamma distribution should be used to model the basic reproductive number.


title: Successful recovery from critical COVID-19 pneumonia with extracorporeal membrane oxygenation: A case report

text: A public health emergency of current international concern is the outbreak of a severe respiratory illness, that is, coronavirus disease (COVID-19). The disease initially started in Wuhan, China, and it rapidly spread to most regions of the world. Herein, we report a case of critical COVID-19 pneumonia treated with extracorporeal membrane oxygenation from symptom onset day 19 (SOD#19) to SOD#30. We describe the patient's clinical course, from mild symptoms at the time of illness onset to symptoms of severe pneumonia as the illness progressed. We provide important information regarding our clinical experience for further understanding of management discrepancies, as treatment with extracorporeal membrane oxygenation or pharmacotherapy (e.g., antivirals, immunomodulators, and glucocorticoids) is often dependent on the severity of symptoms.


title: Neuraxial anaesthesia and peripheral nerve blocks during the COVID‐19 pandemic: a literature review and practice recommendations

text: Coronavirus disease 2019 (COVID‐19) has had a significant impact on global healthcare services. In an attempt to limit the spread of infection and to preserve healthcare resources, one commonly used strategy has been to postpone elective surgery, whilst maintaining the provision of anaesthetic care for urgent and emergency surgery. General anaesthesia with airway intervention leads to aerosol generation, which increases the risk of COVID‐19 contamination in operating rooms and significantly exposes the healthcare teams to COVID‐19 infection during both tracheal intubation and extubation. Therefore, the provision of regional anaesthesia may be key during this pandemic, as it may reduce the need for general anaesthesia and the associated risk from aerosol‐generating procedures. However, guidelines on the safe performance of regional anaesthesia in light of the COVID‐19 pandemic are limited. The goal of this review is to provide up‐to‐date, evidence‐based recommendations or expert opinion when evidence is limited, for performing regional anaesthesia procedures in patients with suspected or confirmed COVID‐19 infection. These recommendations focus on seven specific domains including: planning of resources and staffing; modifying the clinical environment; preparing equipment, supplies and drugs; selecting appropriate personal protective equipment; providing adequate oxygen therapy; assessing for and safely performing regional anaesthesia procedures; and monitoring during the conduct of anaesthesia and post‐anaesthetic care. Implicit in these recommendations is preserving patient safety whilst protecting healthcare providers from possible exposure.


title: Identification of single-chain antibody fragments specific against SARS-associated coronavirus from phage-displayed antibody library

text: Abstract To develop early diagnostic reagents, effective vaccines, and even drugs against SARS-associated coronavirus (SARS-CoV), the human single fold single-chain antibody fragments, (scFv) libraries I+J (Tomlinson I+J) were used to identify novel scFvs, which can specifically bind to SARS-CoV. Interestingly, two scFvs (B5 and B9) exhibited higher binding specificity to SARS-CoV with the OD450 value 0.608 and 0.545, respectively, and their coding sequences shared the identical sequence composed of VH gene (351bp) and VL gene (327bp), so the two scFvs were uniformly named as SA59B and chosen for further analysis. SA59B scFv was expressed in soluble form in Escherichia coli HB2151 and purified by immobilized metal affinity chromatography. The soluble 30kDa SA59B scFv-antibody was verified in SDS–PAGE and Western-blot. The purified SA59B scFv-antibody was labeled with HRP by the glutaraldehyde method, and the concentration of HRP and SA59B scFv-antibody in the SA59B-HRP solution reached 2.4 and 2.28mg/ml, respectively. Then, the binding ability of SA59B-HRP to SARS-CoV was evaluated by ELISA with S/N of 11.6, indicating higher binding specificity between them. Finally, both the SA59B sequence specificity and its application for diagnosis, prophylaxis or therapy of SARS were discussed.


title: In-hospital cardiac arrest outcomes among patients with COVID-19 pneumonia in Wuhan, China

text: OBJECTIVE: To describe the characteristics and outcomes of patients with severe COVID-19 and in-hospital cardiac arrest (IHCA) in Wuhan, China. METHODS: The outcomes of patients with severe COVID-19 pneumonia after IHCA over a 40-day period were retrospectively evaluated. Between January 15 and February 25, 2020, data for all cardiopulmonary resuscitation (CPR) attempts for IHCA that occurred in a tertiary teaching hospital in Wuhan, China were collected according to the Utstein style. The primary outcome was restoration of spontaneous circulation (ROSC), and the secondary outcomes were 30-day survival, and neurological outcome. RESULTS: Data from 136 patients showed 119 (87.5%) patients had a respiratory cause for their cardiac arrest, and 113 (83.1%) were resuscitated in a general ward. The initial rhythm was asystole in 89.7%, pulseless electrical activity (PEA) in 4.4%, and shockable in 5.9%. Most patients with IHCA were monitored (93.4%) and in most resuscitation (89%) was initiated <1 min. The average length of hospital stay was 7 days and the time from illness onset to hospital admission was 10 days. The most frequent comorbidity was hypertension (30.2%), and the most frequent symptom was shortness of breath (75%). Of the patients receiving CPR, ROSC was achieved in 18 (13.2%) patients, 4 (2.9%) patients survived for at least 30 days, and one patient achieved a favourable neurological outcome at 30 days. Cardiac arrest location and initial rhythm were associated with better outcomes. CONCLUSION: Survival of patients with severe COVID-19 pneumonia who had an in-hospital cardiac arrest was poor in Wuhan.


title: Dietary Plasma Protein Affects the Immune Response of Weaned Rats Challenged with S. aureus Superantigen B

text: The aim of this study was to determine the potential modulatory effects of diets supplemented with spray-dried animal plasma (SDAP) or immunoglobulin concentrates (IC) on the immune response of rats challenged with Staphylococcus aureus enterotoxin B (SEB). Lewis rats were fed diets containing 80 g of SDAP/kg diet, 22.7 g of IC/kg diet, or milk proteins (Control diet) from postnatal d 21 (weaning) for 14 d. On d 30 and 33, rats were given SEB (0.5 mg/kg body weight; i.p.). Organized gut-associated lymphoid tissue (GALT) populations, intestinal secretion, mucosal and serum immunoglobulin concentrations, and neutrophil infiltration were studied. On d 35, blood was collected under anesthesia and samples of intestinal mucosa, Peyer's patches, mesenteric lymph nodes (MLN), and spleen were taken. SEB increased the water content of feces, which was prevented by diets containing either SDAP (P < 0.002) or IC (P < 0.001), indicating that plasma protein–supplemented diets can reverse the SEB-induced secretory response. In Peyer's patches, the diet containing SDAP partially prevented the SEB-induced increase in T lymphocytes (P < 0.1) and reduced the percentage of activated T helper cells (P < 0.05). In MLN, activated T lymphocytes were increased by SEB but they were not affected by diet. No effects of SEB or dietary supplementation on mucosal IgA and serum IgA and IgG were observed. The effects of SDAP supplementation on the lymphocyte populations of GALT in rats challenged with SEB support the view that SDAP can modulate the immune response and suggest that plasma protein supplementation can prevent GALT from possible activation by luminal bacterial superantigens.


title: Estimating Variability in the Transmission of Severe Acute Respiratory Syndrome to Household Contacts in Hong Kong, China

text: The extensive data collection and contact tracing that occurred during the 2003 outbreak of severe acute respiratory syndrome (SARS) in Hong Kong, China, allowed the authors to examine how the probability of transmission varied from the date of symptom onset to the date of hospitalization for household contacts of SARS patients. Using a discrete-time likelihood model, the authors estimated the transmission probability per contact for each day following the onset of symptoms. The results suggested that there may be two peaks in the probability of SARS transmission, the first occurring around day 2 after symptom onset and the second occurring approximately 10 days after symptom onset. Index patients who were aged 60 years or older or whose lactate dehydrogenase level was elevated upon admission to the hospital (indicating higher viral loads) were more likely to transmit SARS to their contacts. There was little variation in the daily transmission probabilities before versus after the introduction of public health interventions on or around March 26, 2003. This study suggests that the probability of transmission of SARS is dependent upon characteristics of the index patients and does not simply reflect temporal variability in the viral load of SARS cases.


title: Pentraxin 3 Detects Clinically Significant Fibrosis in Patients with Chronic Viral Hepatitis C

text: Pentraxin 3 (PTX3) plays a pathogenic role in experimental models of chronic liver injury and contributes to the progression of fibrosis. The detection of advanced fibrosis (METAVIR F≥3) is important to identify patients who are in urgent need of antiviral treatments versus those whose treatment could be deferred (F≥2). The aim was to assess the diagnostic value of PTX3 as a potential biomarker for clinically significant and advanced fibrosis. PTX3 associations with biochemical and histological parameters of inflammatory activity and fibrosis were investigated in 138 patients with chronic viral hepatitis C (HCV) before antiviral treatment. METAVIR histological scores of activity and fibrosis were obtained. PTX3 was measured by enzyme-linked immunosorbent assay. The diagnostic accuracy of serum PTX3 levels was compared to that of other fibrosis markers, including transforming growth factor‐β(1) (TGF-β(1)), hyaluronic acid (HA), aspartate transaminase to platelet ratio index (APRI), fibrosis score based on four factors (FIB4), gamma-glutamyltranspeptidase to platelet ratio (GPR), and the liver stiffness measurement (LSM) by transient elastography (FibroScan®). In HCV patients the PTX3 level increased in parallel with the METAVIR histological score of activity, being independently associated with the METAVIR fibrosis score (P < 0.001). Using the receiver operating characteristics analysis, the best marker for detecting F≥2 and F≥3 was PTX3 with AUC = 0.802 and AUC = 0.867, respectively. The area under the curve of PTX3 for predicting significant fibrosis (F≥2) was significantly greater than those for the GPR ratio (AUC = 0.648) and FIB-4 score (AUC = 0.770) and similar to that for APRI index (AUC = 0.831). PTX3 provided clinically relevant diagnostic accuracy as a single marker of significant fibrosis.


title: Social determinants, ethical issues and future challenge of tuberculosis in a pluralistic society: the example of Israel

text: Tuberculosis is a very serious respiratory infectious disease, caused by the bacillus Mycobacterium tuberculosis, which generates a relevant societal and clinical burden. It has always represented a permanent concern and a public health challenge over the course of human history, because of its severe epidemiological, and economic-financial implications. The present review aims at over-viewing the impact of tuberculosis on the Israeli healthcare system, its temporal trend and evolution, stratified according to ethnicities and minorities, the need of establishing new facilities and implementing screening techniques, public health strategies and diagnostic tests, following massive immigration waves from countries characterized by a high incidence rate of tuberculosis during the fifties-sixties until the nineties, and the policies implemented by the Israeli government in the control, management and treatment of tuberculosis, as well as the role played by Israeli prominent scientists in discovering new druggable targets and finding bioactive compounds and bio-molecules in the fight against tuberculosis. Israel represents a unique, living laboratory in which features of developed and developing countries mix together. This country as a case-study of immigrant, pluralistic society underlines the importance of adopting a culturally-sensitive community intervention approach. The understanding of the subtle interplay between race/ethnic host and pathogen factors, including the role of gene variations and polymorphisms can pave the way for a personalized treatment and management of tuberculosis patients, contributing to the development of new tools for targeted tuberculosis therapeutics, immunodiagnostics and vaccination products.


title: Crystallization and preliminary X-ray diffraction studies of infectious bronchitis virus nonstructural protein 9

text: Avian infectious bronchitis virus (IBV), which causes respiratory disease in infected birds, belongs to coronavirus group 3. IBV encodes 15 nonstructural proteins (nsp2–nsp16) which play crucial roles in RNA transcription and genome replication. Nonstructural protein 9 (nsp9) has been identified as a protein that is essential to viral replication because of its single-stranded RNA-binding ability. The gene segment encoding IBV nsp9 has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted X-rays to 2.44 Å resolution. They belonged to the cubic space group I432, with unit-cell parameters a = b = c = 123.4 Å, α = β = γ = 90°. The asymmetric unit appeared to contain one molecule, with a solvent content of 62% (V (M) = 3.26 Å(3) Da(−1)).


title: Epidemiological survey of enteric viruses in wild boars in the Czech Republic: First evidence of close relationship between wild boar and human rotavirus A strains

text: Abstract Population of wild boar is increasing in the whole Europe, the animals migrate close to human habitats which greatly increases the possibility of natural transmission between domestic animals or humans and wild boars. The aim of the study was to estimate in population of free-living wild boar in the Czech Republic the prevalence of enteric viral pathogens, namely rotavirus groups A and C (RVA and RVC), porcine reproductive and respiratory syndrome virus (PRRSV), and members of family Coronaviridae (transmissible gastroenteritis virus – TGEV, porcine epidemic diarrhea virus − PEDV, porcine respiratory coronavirus – PRCV, and porcine hemagglutination encephalomyelitis virus – PHEV) and Picornaviridae,(teschovirus A – PTV, sapelovirus A – PSV, and enterovirus G – EV-G). In our study, stool samples from 203 wild boars culled during hunting season 2014–2015 (from October to January) were examined by RT-PCR. RVA was detected in 2.5% of tested samples. Nucleotide analysis of VP7, VP4, and VP6 genes revealed that four RVA strains belong to G4P[25]I1, G4P[6]I5, G11P[13]I5, and G5P[13]I5 genotypes and phylogenetic analysis suggested close relation to porcine and human RVAs. The prevalence of RVC in wild boar population reached 12.8%, PTV was detected in 20.2%, PSV in 8.9%, and EV-G in 2.5% of samples. During our study no PRRSV or coronaviruses were detected. Our study provides the first evidence of RVC prevalence in wild boars and indicates that wild boars might contribute to the genetic variability of RVA and also serve as an important reservoir of other enteric viruses.


Performance of FilmArray RP2 Multiplex Panel for identification of MERS CoV


title: GSK3: A Kinase Balancing Promotion and Resolution of Inflammation

text: GSK3 has been implicated for years in the regulation of inflammation and addressed in a plethora of scientific reports using a variety of experimental (disease) models and approaches. However, the specific role of GSK3 in the inflammatory process is still not fully understood and controversially discussed. Following a detailed overview of structure, function, and various regulatory levels, this review focusses on the immunoregulatory functions of GSK3, including the current knowledge obtained from animal models. Its impact on pro-inflammatory cytokine/chemokine profiles, bacterial/viral infections, and the modulation of associated pro-inflammatory transcriptional and signaling pathways is discussed. Moreover, GSK3 contributes to the resolution of inflammation on multiple levels, e.g., via the regulation of pro-resolving mediators, the clearance of apoptotic immune cells, and tissue repair processes. The influence of GSK3 on the development of different forms of stimulation tolerance is also addressed. Collectively, the role of GSK3 as a kinase balancing the initiation/perpetuation and the amelioration/resolution of inflammation is highlighted.


title: A Novel Replication-Competent Vaccinia Vector MVTT Is Superior to MVA for Inducing High Levels of Neutralizing Antibody via Mucosal Vaccination

text: Mucosal vaccination offers great advantage for inducing protective immune response to prevent viral transmission and dissemination. Here, we report our findings of a head-to-head comparison of two viral vectors modified vaccinia Ankara (MVA) and a novel replication-competent modified vaccinia Tian Tan (MVTT) for inducing neutralizing antibodies (Nabs) via intramuscular and mucosal vaccinations in mice. MVTT is an attenuated variant of the wild-type VTT, which was historically used as a smallpox vaccine for millions of Chinese people. The spike glycoprotein (S) of SARS-CoV was used as the test antigen after the S gene was constructed in the identical genomic location of two vectors to generate vaccine candidates MVTT-S and MVA-S. Using identical doses, MVTT-S induced lower levels (∼2-3-fold) of anti- SARS-CoV neutralizing antibodies (Nabs) than MVA-S through intramuscular inoculation. MVTT-S, however, was capable of inducing consistently 20-to-100-fold higher levels of Nabs than MVA-S when inoculated via either intranasal or intraoral routes. These levels of MVTT-S-induced Nab responses were substantially (∼10-fold) higher than that induced via the intramuscular route in the same experiments. Moreover, pre-exposure to the wild-type VTT via intranasal or intraoral route impaired the Nab response via the same routes of MVTT-S vaccination probably due to the pre-existing anti-VTT Nab response. The efficacy of intranasal or intraoral vaccination, however, was still 20-to-50-fold better than intramuscular inoculation despite the subcutaneous pre-exposure to wild-type VTT. Our data have implications for people who maintain low levels of anti-VTT Nabs after historical smallpox vaccination. MVTT is therefore an attractive live viral vector for mucosal vaccination.


title: Structural Complexity of DNA Sequence

text: In modern bioinformatics, finding an efficient way to allocate sequence fragments with biological functions is an important issue. This paper presents a structural approach based on context-free grammars extracted from original DNA or protein sequences. This approach is radically different from all those statistical methods. Furthermore, this approach is compared with a topological entropy-based method for consistency and difference of the complexity results.


title: Disease X: accelerating the development of medical countermeasures for the next pandemic

text: Summary WHO has listed several priority diseases with epidemic potential for which there are no, or insufficient, medical countermeasures. In response, the Bill & Melinda Gates Foundation (with support from PricewaterhouseCoopers) coordinated subject matter experts to create a preparedness plan for Disease X. Disease X is caused by Pathogen X, an infectious agent that is not currently known to cause human disease, but an aetiologic agent of a future outbreak with epidemic or pandemic potential. We have identified crucial areas for acceleration in medical countermeasure product development and international coordination. We have also reviewed novel platforms and process improvements related to manufacturing, which could revolutionise the response to the next pandemic. Finally, we created several coordination and engagement guides. These guides range from the rational design of an intervention target product profile, to the key facets of vaccine and therapeutic development, to accelerated manufacturing and regulatory mechanisms. In this Personal View, we provide a high-level summary of the outcomes of the medical countermeasure development workstream, intended for a broad audience including academia, medical countermeasure developers, and multilateral coordinating bodies. We hope that they might find this piece useful in prioritising strategic investments and efforts to accelerate medical countermeasure development. We observed that in-depth analyses of clinical trial design, chemistry, manufacturing and control activities, and accelerated regulatory pathways are necessary for shortening the timelines for the product development of medical countermeasures. We intend to cover these topics in future publications.


title: Giardia is the most prevalent parasitic infection in dogs and cats with diarrhea in the city of Medellín, Colombia

text: Abstract Parasitic agents are a common cause of diarrhea in dogs and cats and, thus, determining their prevalence is essential to establish preventive and control measures. This retrospective study examined the fecal tests records from 1111 dogs and 203 cats with diarrhea submitted to a diagnostic laboratory in the city of Medellin between January and May 2018. The detection of parasites was carried out by direct smears and simple flotation methods. Parasitic organisms were detected in feces from 464 (41.7%) dogs and 96 (47.3%) cats. In order of decreasing prevalence, the parasites detected in dogs were: Giardia intestinalis (13%), ancylostomids (12.6%), Entamoeba spp. (6.1%), coccidian oocysts (5.8%), Toxocara spp. (5.6%) and Dipylidium caninum (1.3%). In cats, the prevalence was: Giardia intestinalis (20%), coccidian oocysts (8.9%), Entamoeba spp. (7.9%), ancylostomids (6.4%), Toxocara spp. (2.5%) and Dipylidium caninum (2%). Age, but not gender, was a predisposing factor, as puppies and kittens had significantly higher infection rates that older age categories. The majority of Giardia intestinalis positive cases occurred in puppies (109/145, 75.2%) and kittens (19/36, 52.8%), making this parasite the most prevalent in amongst animals with diarrhea. Out of 117 positive infections in the adult dog population, ancylostomids accounted for 56 cases (47.9%) and was the most common parasite in this age group. In conclusion, although these results do not imply a cause and effect relationship, they are an estimate of the type of parasites that may be most commonly associated with diarrhea in dogs and cats. The lower diagnostic sensitivity of the traditional methods used here as compared to more contemporary techniques like fecal flotation with centrifugation and PCR, may have underestimated the actual prevalence and diminished the detection of co-infections. Future studies should aim to have diagnostic panels that also screen for other enteric pathogens, including bacterial and viral agents.


The Impact of Covid‐19 Pandemic on Elderly Mental Health


Emerging and Reemerging Infectious Diseases


title: EAN congress highlights challenges — predict, prevent, repair

text: After going virtual, the European Academy of Neurology 2020 Congress became the biggest neurology meeting in history. The overarching theme was ‘Time for action: predict, prevent, repair’ — three upcoming Reviews in Nature Reviews Neurology, written by speakers at the congress, highlight the importance of the theme across neurology.


title: Presence of specific viruses in the middle ear fluids and respiratory secretions of young children with acute otitis media

text: The purpose of the study was to investigate the presence of different viruses in middle ear fluids and nasopharyngeal aspirates in young children with acute otitis media. Two cohorts of children (N = 329 and 611) were followed from 2 to 24 months of age in Finland in two prospective studies (Finnish Otitis Media Cohort Study and Finnish Otitis Media Vaccine Trial). During the study period, nasopharyngeal and middle ear fluid specimens for each acute otitis media event were examined for eight (Cohort Study) or ten (Vaccine Trial) common respiratory viruses; adenoviruses, influenza viruses A and B, parainfluenza viruses 1, 2, and 3, respiratory syncytial virus (RSV), enteroviruses, parechoviruses, and rhinoviruses. Picornaviruses (rhinoviruses, enteroviruses, and parechoviruses) were determined by reverse transcription PCR while antigen detection was used for the other viruses. A virus was present in either nasopharyngeal or middle ear specimen in 54% of events in the first cohort and in 67% of events in the second. Rhinoviruses formed the most common virus group detected (41–32%), followed by enteroviruses (25%, sought in the second cohort only) and respiratory syncytial virus (RSV) (10%). All the other viruses represented jointly 8–10% of the events. In conclusion, using the methods described in this study, a specific virus infection was diagnosed in two thirds of all acute otitis media events in young children. Picornavirus RNA was detected in association with more than a half of all acute otitis media events. The use of PCR‐based methods for the other respiratory viruses might have increased further the overall virus detection rate in acute otitis media. J. Med. Virol. 72:241–248, 2004. © 2004 Wiley‐Liss, Inc.


title: Partial deletion in the spike endodomain of mouse hepatitis virus decreases the cytopathic effect but maintains foreign protein expression in infected cells

text: Abstract Mouse hepatitis virus (MHV) produces a series of subgenomic RNAs for viral protein expression. As a prototype coronavirus, MHV has been explored extensively and is often used to express foreign proteins. Previously, a 13-residue deletion in the MHV spike (S) protein endodomain was found to reduce syncytium formation dramatically while inhibiting virus replication slightly. In this study, the effects of the S mutation on MHV infectivity and foreign protein expression were further examined in rat or mouse L2, NIH/3T3 and Neuro-2a cells. The replacement of the MHV 2a/haemagglutinin-esterase gene with a membrane-anchored protein hook (HK) and replacement of gene 4 with EGFP did not change the adaptability and cytopathology of recombinant viruses in these cells. However, the cytopathic effect of the recombinants with the partial S deletion was reduced significantly in these cells. The replication and foreign protein expression of the S-mutated recombinants were found to be more efficient in L2 cells than in Neuro-2a and NIH/3T3 cells. Meanwhile, the distribution patterns of HK and EGFP expressed by the recombinant viruses were similar to those in cells transfected with a eukaryotic expression vector. These results suggest that the partial deletion in the S endodomain may increase the usefulness of MHV as a viral vector by attenuation and maintaining foreign protein expression.


title: The antimalarial ferroquine is an inhibitor of hepatitis C virus,

text: Hepatitis C virus (HCV) is a major cause of chronic liver disease. Despite recent success in improving anti‐HCV therapy, additional progress is still needed to develop cheaper and interferon (IFN)‐free treatments. Here, we report that ferroquine (FQ), an antimalarial ferrocenic analog of chloroquine, is a novel inhibitor of HCV. FQ potently inhibited HCV infection of hepatoma cell lines by affecting an early step of the viral life cycle. The antiviral activity of FQ on HCV entry was confirmed with pseudoparticles expressing HCV envelope glycoproteins E1 and E2 from six different genotypes. In addition to its effect on HCV entry, FQ also inhibited HCV RNA replication, albeit at a higher concentration. We also showed that FQ has no effect on viral assembly and virion secretion. Using a binding assay at 4°C, we showed that FQ does not prevent attachment of the virus to the cell surface. Furthermore, virus internalization was not affected by FQ, whereas the fusion process was impaired in the presence of FQ as shown in a cell‐cell fusion assay. Finally, virus with resistance to FQ was selected by sequential passage in the presence of the drug, and resistance was shown to be conferred by a single mutation in E1 glycoprotein (S327A). By inhibiting cell‐free virus transmission using a neutralizing antibody, we also showed that FQ inhibits HCV cell‐to‐cell spread between neighboring cells. Combinations of FQ with IFN, or an inhibitor of HCV NS3/4A protease, also resulted in additive to synergistic activity. Conclusion: FQ is a novel, interesting anti‐HCV molecule that could be used in combination with other direct‐acting antivirals. (Hepatology 2013)


title: Epidemiology of two human protoparvoviruses, bufavirus and tusavirus

text: Two human parvoviruses were recently discovered by metagenomics in Africa, bufavirus (BuV) in 2012 and tusavirus (TuV) in 2014. These viruses have been studied exclusively by PCR in stool and detected only in patients with diarrhoea, although at low prevalence. Three genotypes of BuV have been identified. We detected, by in-house EIA, BuV1-3 IgG antibodies in 7/228 children (3.1%) and 10/180 adults (5.6%), whereas TuV IgG was found in one child (0.4%). All children and 91% of the adults were Finnish, yet interestingly 3/6 adults of Indian origin were BuV-IgG positive. By competition EIA, no cross-reactivity between the BuVs was detected, indicating that the BuV genotypes represent distinct serotypes. Furthermore, we analysed by BuV qPCR stool and nasal swab samples from 955 children with gastroenteritis, respiratory illness, or both, and found BuV DNA in three stools (0.3%) and for the first time in a nasal swab (0.1%). This is the first study documenting the presence of BuV and TuV antibodies in humans. Although the seroprevalences of both viruses were low in Finland, our results indicate that BuV infections might be widespread in Asia. The BuV-specific humoral immune responses appeared to be strong and long-lasting, pointing to systemic infection in humans.


title: Incidence of respiratory viruses in peruvian children with acute respiratory infections

text: Acute respiratory infections are responsible for high morbi–mortality in Peruvian children. However, the etiological agents are poorly identified. This study, conducted during the pandemic outbreak of H1N1 influenza in 2009, aims to determine the main etiological agents responsible for acute respiratory infections in children from Lima, Peru. Nasopharyngeal swabs collected from 717 children with acute respiratory infections between January 2009 and December 2010 were analyzed by multiplex RT‐PCR for 13 respiratory viruses: influenza A, B, and C virus; parainfluenza virus (PIV) 1, 2, 3, and 4; and human respiratory syncytial virus (RSV) A and B, among others. Samples were also tested with direct fluorescent‐antibodies (DFA) for six respiratory viruses. RT‐PCR and DFA detected respiratory viruses in 240 (33.5%) and 85 (11.9%) cases, respectively. The most common etiological agents were RSV‐A (15.3%), followed by influenza A (4.6%), PIV‐1 (3.6%), and PIV‐2 (1.8%). The viruses identified by DFA corresponded to RSV (5.9%) and influenza A (1.8%). Therefore, respiratory syncytial viruses (RSV) were found to be the most common etiology of acute respiratory infections. The authors suggest that active surveillance be conducted to identify the causative agents and improve clinical management, especially in the context of possible circulation of pandemic viruses. J. Med. Virol. 87:917–924, 2015. © 2015 Wiley Periodicals, Inc.


title: Management and Outcomes of Critically-III Patients with COVID-19 Pneumonia at a Safety-net Hospital in San Francisco, a Region with Early Public Health Interventions: A Case Series

text: BACKGROUND: Following early implementation of public health measures, San Francisco has experienced a slow rise and a low peak level of coronavirus disease 2019 (COVID-19) cases and deaths. METHODS AND FINDINGS: We included all patients with COVID-19 pneumonia admitted to the intensive care unit (ICU) at the safety net hospital for San Francisco through April 8, 2020. Each patient had ≥15 days of follow-up. Among 26 patients, the median age was 54 years (interquartile range, 43 to 62), 65% were men, and 77% were Latinx. Mechanical ventilation was initiated for 11 (42%) patients within 24 hours of ICU admission and 20 patients (77%) overall. The median duration of mechanical ventilation was 13.5 days (interquartile range, 5 to 20). Patients were managed with lung protective ventilation (tidal volume ≤8 ml/kg of ideal body weight and plateau pressure ≤30 cmH(2)O on 98% and 78% of ventilator days, respectively). Prone positioning was used for 13 of 20 (65%) ventilated patients for a median of 5 days (interquartile range, 2 to 10). Seventeen (65%) patients were discharged home, 1 (4%) was discharged to nursing home, 3 (12%) were discharged from the ICU, and 2 (8%) remain intubated in the ICU at the time of this report. Three (12%) patients have died. CONCLUSIONS: Good outcomes were achieved in critically ill patients with COVID-19 by using standard therapies for acute respiratory distress syndrome (ARDS) such as lung protective ventilation and prone positioning. Ensuring hospitals can deliver sustained high-quality and evidence-based critical care to patients with ARDS should remain a priority.


title: Distribution of the Phenotypic Effects of Random Homologous Recombination between Two Virus Species

text: Recombination has an evident impact on virus evolution and emergence of new pathotypes, and has generated an immense literature. However, the distribution of phenotypic effects caused by genome-wide random homologous recombination has never been formally investigated. Previous data on the subject have promoted the implicit view that most viral recombinant genomes are likely to be deleterious or lethal if the nucleotide identity of parental sequences is below 90%. We decided to challenge this view by creating a bank of near-random recombinants between two viral species of the genus Begomovirus (Family Geminiviridae) exhibiting 82% nucleotide identity, and by testing infectivity and in planta accumulation of recombinant clones randomly extracted from this bank. The bank was created by DNA-shuffling—a technology initially applied to the random shuffling of individual genes, and here implemented for the first time to shuffle full-length viral genomes. Together with our previously described system allowing the direct cloning of full-length infectious geminivirus genomes, it provided a unique opportunity to generate hundreds of “mosaic” virus genomes, directly testable for infectivity. A subset of 47 randomly chosen recombinants was sequenced, individually inoculated into tomato plants, and compared with the parental viruses. Surprisingly, our results showed that all recombinants were infectious and accumulated at levels comparable or intermediate to that of the parental clones. This indicates that, in our experimental system, despite the fact that the parental genomes differ by nearly 20%, lethal and/or large deleterious effects of recombination are very rare, in striking contrast to the common view that has emerged from previous studies published on other viruses.


title: The Coronavirus PEDV Evades Type III Interferon Response Through the miR-30c-5p/SOCS1 Axis

text: Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen that has evolved several mechanisms to evade type I IFN responses. Type III interferon (IFN-λ), an innate cytokine that primarily targets the mucosal epithelia, is critical in fighting mucosal infection in the host and has been reported to potently inhibit PEDV infection in vitro. However, how PEDV escapes IFN-λ antiviral response remains unclear. In this study, we found that PEDV infection induced significant IFN-λ expression in type I IFN-defective Vero E6 cells, but virus-induced endogenous IFN-λ did not reduce PEDV titers. Moreover, we demonstrated that PEDV escaped IFN-λ responses by substantially upregulating the suppressor of cytokine signaling protein 1 (SOCS1) expression, which impaired the induction of IFN-stimulated genes (ISGs) and dampened the IFN-λ antiviral response and facilitated PEDV replication in Vero E6 cells. We further showed that PEDV infection increased SOCS1 expression by decreasing host miR-30c-5p expression. MiR-30c-5p suppressed SOCS1 expression through targeting the 3′ untranslated region (UTR) of SOCS1. The inhibition of IFN-λ elicited ISGs expression by SOCS1 was specifically rescued by overexpression of miR-30c-5p. Collectively, our findings identify a new strategy by PEDV to escape IFN-λ-mediated antiviral immune responses by engaging the SOCS1/miR-30c axis, thus improving our understanding of its pathogenesis.


title: Reply: “Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020, 12(4), 988”

text: We thank Dr [...].


title: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Dromedary Camels in Africa and Middle East

text: Dromedary camels are the natural reservoirs of the Middle East respiratory syndrome coronavirus (MERS-CoV). Camels are mostly bred in East African countries then exported into Africa and Middle East for consumption. To understand the distribution of MERS-CoV among camels in North Africa and the Middle East, we conducted surveillance in Egypt, Senegal, Tunisia, Uganda, Jordan, Saudi Arabia, and Iraq. We also performed longitudinal studies of three camel herds in Egypt and Jordan to elucidate MERS-CoV infection and transmission. Between 2016 and 2018, a total of 4027 nasal swabs and 3267 serum samples were collected from all countries. Real- time PCR revealed that MERS-CoV RNA was detected in nasal swab samples from Egypt, Senegal, Tunisia, and Saudi Arabia. Microneutralization assay showed that antibodies were detected in all countries. Positive PCR samples were partially sequenced, and a phylogenetic tree was built. The tree suggested that all sequences are of clade C and sequences from camels in Egypt formed a separate group from previously published sequences. Longitudinal studies showed high seroprevalence in adult camels. These results indicate the widespread distribution of the virus in camels. A systematic active surveillance and longitudinal studies for MERS-CoV are needed to understand the epidemiology of the disease and dynamics of viral infection.


title: Coronavirus disease (COVID‐19): An updated review based on current knowledge and existing literature for dermatologists

text: The world entered the year 2020 with reports of the emergence of a new viral illness in Wuhan city, Hubei province, China. In January 2020, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified to be the causative novel coronavirus for the cluster of patients suffering from pneumonia in China. The disease was later named as coronavirus disease (COVID‐19) and was declared a pandemic by the World Health Organization on March 11, 2020. Several studies, since then, have tried to study and explain the origin of SARS‐CoV‐2, its structure and pathogenicity, epidemiology, modes of transmission, spectrum of illness and causes of mortality and morbidity. The current management strategies focus on supportive care and prevention of complications. With no definite treatment, as of now, encouraging reports of some anti‐viral and anti‐malarial drugs in the management of COVID‐19 generate some hope. This review intends to cover the current known aspects of COVID‐19 and SARS‐CoV‐19, based on the available literature.


title: Epidemiology of 11 respiratory RNA viruses in a cohort of hospitalized children in Riyadh, Saudi Arabia

text: Respiratory tract infections are a principal cause of illness and mortality in children worldwide and mostly caused by viruses. In this study, the epidemiology of 11 respiratory RNA viruses was investigated in a cohort of hospitalized children at a tertiary referral center in Riyadh from February 2008 to March 2009 using conventional and real‐time monoplex RT‐PCR assays. Among 174 nasopharyngeal aspirates, respiratory syncytial virus (RSV) was detected in 39 samples (22.41%), influenza A virus in 34 (19.54%), metapneumovirus (MPV) in 19 (10.92%), coronaviruses in 14 (8.05%), and parainfluenza viruses (PIVs) in 11 (6.32%). RSV, PIVs and coronaviruses were most prevalent in infants less than 6 months old, whereas MPV and influenza A virus were more prominent in children aged 7–24 and 25–60 months, respectively. The majority of the viruses were identified during winter with two peaks observed in March 2008 and January 2009. The presented data warrants further investigation to understand the epidemiology of respiratory viruses in Saudi Arabia on spatial and temporal basis. J. Med. Virol. 88:1086–1091, 2016. © 2015 Wiley Periodicals, Inc.


title: Chapter 4 Virus-Like Particle and Nanoparticle Vaccines

text: Abstract Atomic-level structural information and advances in synthetic biology and nanotechnology have created new opportunities for generating vaccines in a way that has not been possible using traditional methods. These novel approaches to recombinant vaccine design are opening doors to the development of vaccines against challenging targets. In this chapter, we discuss the exceptional humoral immunogenicity of virus-like particles (VLPs) and related nanoparticles and their application to vaccine development. The emergence of this new category of vaccine platforms is based on recent insights from multiple fields of study, including immunology, virology, nanotechnology, structural biology, synthetic biology, and bioengineering. The multidisciplinary work on VLP and nanoparticle immunogens is already yielding dividends for public health, but is also likely to result in safer, more potent and broadly protective vaccines against a wide variety of human and animal pathogens, as well as target host proteins of interest.


title: Chapter Three Climate Change and the Neglected Tropical Diseases

text: Abstract Climate change is expected to impact across every domain of society, including health. The majority of the world's population is susceptible to pathological, infectious disease whose life cycles are sensitive to environmental factors across different physical phases including air, water and soil. Nearly all so-called neglected tropical diseases (NTDs) fall into this category, meaning that future geographic patterns of transmission of dozens of infections are likely to be affected by climate change over the short (seasonal), medium (annual) and long (decadal) term. This review offers an introduction into the terms and processes deployed in modelling climate change and reviews the state of the art in terms of research into how climate change may affect future transmission of NTDs. The 34 infections included in this chapter are drawn from the WHO NTD list and the WHO blueprint list of priority diseases. For the majority of infections, some evidence is available of which environmental factors contribute to the population biology of parasites, vectors and zoonotic hosts. There is a general paucity of published research on the potential effects of decadal climate change, with some exceptions, mainly in vector-borne diseases.


title: Effect of early pregnancy diagnosis by per rectum amniotic sac palpation on pregnancy loss, calving rates, and abnormalities in newborn dairy calves

text: The objectives of the present study were to evaluate the effect of per rectal amniotic sac palpation (ASP) for pregnancy diagnosis during the late embryonic period on pregnancy loss, calving rates, and abnormalities in newborn calves. A controlled, randomized, blocked, blind experiment containing 680 lactating pregnant dairy cows with a viable embryo diagnosed by transrectal ultrasonography was performed. Two dairy operation sites (farm A and farm B) were selected. At each farm, the cows were randomly divided into control (CON) and ASP groups. The CON group was not subjected to pregnancy diagnosis via per rectum palpation. The ASP examinations were performed by one experienced veterinarian between Days 34 and 45 after breeding. All cows were reevaluated by transrectal ultrasonography only between 2 and 4 weeks later. Two calving rates were calculated: calving rate 1 (cows that calved from the initial number of pregnant cows) and calving rate 2 (cows that calved from cows pregnant at reexamination). In farm A, the percentages of early pregnancy loss were 11.5% (19 of 165) and 13.2% (24 of 182) for the CON and the ASP groups, respectively (P = 0.64). In farm B, the percentage of early pregnancy loss was 11.2% (19 of 170) for the CON group and 8.8% (14 of 159; P = 0.48) for the ASP group. In farm A, the percentage of late pregnancy loss was 7.6% (11 of 145) for the CON group and 5.5% (8 of 155; P = 0.39) for the ASP group. In farm B, the percentage of late pregnancy loss was 3.7% (5 of 137) for the CON group and 6.3% (8 of 127; P = 0.32) for the ASP group. In farm A, early pregnancy loss was higher than late pregnancy loss (12.4% vs. 6.3%; P = 0.01), and in farm B, the same tendency was detected (10.0% vs. 4.9%, for early and late pregnancy loss, respectively; P = 0.02). In farm A, calving rate 1 was 81.2% (134 of 165) for the CON group and 80.8% (147 of 182; P = 0.92) for the ASP group. Calving rate 2 for the same groups was 92.4% (134 of 145) and 94.8% (147 of 155), respectively (P = 0.68). In farm B, calving rate 1 was 77.7% (132 of 170) for the CON group and 74.8% (119 of 159; P = 0.55) for the ASP group. Calving rates 2 for the same groups were 87.4% (132 of 151) and 82.1% (119 of 145), respectively (P = 0.20). Two female calves with atresia coli were diagnosed only in the CON group. It was concluded that ASP during the late embryonic period for pregnancy diagnosis did not increase the pregnancy loss, affect calving rates, or produce abnormalities in calves.


title: Cross-protective immunity to porcine reproductive and respiratory syndrome virus by intranasal delivery of a live virus vaccine with a potent adjuvant

text: Abstract Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive chronic respiratory viral disease of pigs that is responsible for major economic losses to the swine industry worldwide. The efficacy of parenteral administration of widely used modified live virus PRRS vaccine (PRRS-MLV) against genetically divergent PRRSV strains remains questionable. Therefore, we evaluated an alternate and proven mucosal immunization approach by intranasal delivery of PRRS-MLV (strain VR2332) with a potent adjuvant to elicit cross-protective immunity against a heterologous PRRSV (strain MN184). Mycobacterium tuberculosis whole cell lysate (Mtb WCL) was chosen as a potent mucosal adjuvant due to its Th1 biased immune response to PRRS-MLV. Unvaccinated pigs challenged with MN184 had clinical PRRS with severe lung pathology; however, vaccinated (PRRS-MLV+ Mtb WCL) pigs challenged with MN184 were apparently healthy. There was a significant increase in the body weight gain in vaccinated compared to unvaccinated PRRSV challenged pigs. Vaccinated compared to unvaccinated, virus-challenged pigs had reduced lung pathology associated with enhanced PRRSV neutralizing antibody titers and reduced viremia. Immunologically, an increased frequency of Th cells, Th/memory cells, γδ T cells, dendritic cells, and activated Th cells and a reduced frequency of T-regulatory cells were detected at both mucosal and systemic sites. Further, reduced secretion of immunosuppressive cytokines (IL-10 and TGF-β) and upregulation of the Th1 cytokine IFN-γ in blood and lungs were detected in mucosally vaccinated, PRRSV-challenged pigs. In conclusion, intranasal immunization of pigs with PRRS-MLV administered with Mtb WCL generated effective cross-protective immunity against PRRSV.


title: Animal-to-Human Viral Transitions: Is SARS-CoV-2 an Evolutionary Successful One?

text: Transmission of viruses from one species to another is not unusual in nature. Despite this, evolutionarily successful transmissions are rare. Such events can cause pandemics and are followed by host–virus coevolution procedures that can increase the fitness potential of viruses. In this perspective article, I recognize eight main types of trans-species viral transmission. I consider two of them as evolutionarily successful, explaining why coronavirus SARS-CoV-2 could be one of them.


title: Ageing and COVID-19: What Is the Role for Elderly People?

text: Italy is one of the oldest countries in Europe and in the world and now it is also one of the first countries that are fighting against COVID-19. In our country, the increasing life expectancy (80.5 for males and 84.9 for females, with a total life expectancy of 82.9) has led to very positive consequences for health and the well-being of elderly people: a very high number of older adults lives and acts independently in their daily life, even if they have one or more than one chronic disease. In the time of COVID-19′s outbreak in Italy, the focus of the media was on elderly people for two main reasons. First, many older people demonstrated a very high civic sense and they were helping society to fight against the pandemic. Second, also in Italy, like in China, the older adults are at higher risk in being infected with COVID-19 and if they get ill, they have a higher risk of death. The balance previously achieved between age-related disorders and a good quality of life and good health is now under high pressure. It is very important to protect elderly people from infection, but also it is important to respect them and to support them in this complex situation. There is a great risk of “ageism”. In agreement with Lloyd-Sherlock and colleagues (2020), in this editorial we propose some hints of analysis, starting from the ongoing experience in Italy.


title: Characterization of initial north American pediatric surgical response to the COVID-19 pandemic()

text: INTRODUCTION: The impact of COVID-19 pandemic on pediatric surgical care systems is unknown. We present an initial evaluation of self-reported pediatric surgical policy changes from hospitals across North America. METHODS: On March 30, 2020, an online open access, data gathering spreadsheet was made available to pediatric surgeons through the American Pediatric Surgical Association (APSA) website, which captured information surrounding COVID-19 related policy changes. Responses from the first month of the pandemic were collected. Open-ended responses were evaluated and categorized into themes and descriptive statistics were performed to identify areas of consensus. RESULTS: Responses from 38 hospitals were evaluated. Policy changes relating to three domains of program structure and care processes were identified: internal structure, clinical workflow, and COVID-19 safety/prevention. Inter-hospital consensus was high for reducing in-hospital staffing, limiting clinical fellow exposure, implementing telehealth for conducting outpatient clinical visits, and using universal precautions for trauma. Heterogeneity in practices existed for scheduling procedures, implementing testing protocols, and regulating use of personal protective equipment. CONCLUSIONS: The COVID-19 pandemic has induced significant upheaval in the usual processes of pediatric surgical care. While policies evolve, additional research is needed to determine the effect of these changes on patient and healthcare delivery outcomes. Level of Evidence. III


title: Pathogenesis of gut virus infection

text: Abstract In summary, the pathogenesis of many gut virus infections remains uncertain. However, human and animal studies indicate that the majority of gut viruses infect villous enterocytes, Viruses appear to have different affinities for enterocytes at different sites on the villus. Infection of enterocytes leads to cell death, extrusion into the lumen, and villous atrophy when the rate of cell production in the crypts cannot keep pace with the rate of enterocyte loss. This results in a reduced surface area as well as impairment of digestive and absorptive functions. This may also result in a net secretory state. All these changes, along with others such as reduced enzymatic activity and reduced epithelial integrity, may contribute to the induction of an acute but transient malabsorptive diarrhoea which may persist until the digestive/absorptive functions of the enterocyte are restored. However, if colonic compensation is sufficient to handle the increased fluid load, diarrhoea may not be evident. The roles of villous ischaemia, altered countercurrent exchanger or altered immune responses still remain uncertain and require further investigation.


title: Effector biology during biotrophic invasion of plant cells

text: Several obligate biotrophic phytopathogens, namely oomycetes and fungi, invade and feed on living plant cells through specialized structures known as haustoria. Deploying an arsenal of secreted proteins called effectors, these pathogens balance their parasitic propagation by subverting plant immunity without sacrificing host cells. Such secreted proteins, which are thought to be delivered by haustoria, conceivably reprogram host cells and instigate structural modifications, in addition to the modulation of various cellular processes. As effectors represent tools to assist disease resistance breeding, this short review provides a bird’s eye view on the relationship between the virulence function of effectors and their subcellular localization in host cells.