title: Prevalence and correlates of influenza vaccination among non-institutionalized elderly people: An exploratory cross-sectional survey

text: Abstract Background Worldwide pandemics of influenza virus caused extensive morbidity and mortality around the world and influenza vaccination is the most effective method for preventing influenza virus infection and its potentially severe complications. A large proportion of the Hong Kong elderly population has not undergone influenza vaccination. An exploration of the correlates will provide significant information to help identify ways of improving vaccination uptake among Chinese elderly people. Objectives To explore the prevalence and correlates of influenza vaccination Hong Kong Chinese elderly people aged 65 or above. To investigate any differences in attitudes toward influenza vaccination among Hong Kong elderly people with different levels of cognitive and physical functioning. Design An exploratory cross-sectional survey with two objective assessments was employed. Settings: Fifteen elderly centers in Hong Kong Special Administrative Region. Participants: A total of 816 Hong Kong Chinese elderly participants were recruited. Methods Face-to-face interviews were adopted to explore the demographic characteristics, perceptions, health status, knowledge, and resources of, and the influence of disease outbreaks on, influenza vaccination. Two objective validated instruments, the Chinese Mini-Mental State Examination (CMMSE) and the Barthel Index-Modified Chinese Version (MCBI) were used to assess the cognitive status and physical functioning of the participants. Results Approximately two in three individuals (62.4%) had undergone influenza vaccination. Lower cognitive and physical functioning scores were found among the non-vaccinated participants. Multivariate logistic regression analyzes revealed the significant correlates associated with influenza vaccination to be consideration of vaccination in the subsequent years (aOR=7.877; p <0.001); consideration of vaccination if all people aged 65 or above were eligible to receive free vaccination (aOR=3.024; p =0.002); the belief that there is a need to receive influenza vaccination following the Severe Acute Respiratory Syndrome (SARS) and avian influenza (aOR=2.413; p =0.001); receiving advice from nursing staff of elderly centers (aOR=7.161; p <0.001); the medical staff of elderly centers (aOR=3.771; p <0.001) or family members or friends (aOR=3.023; p =0.001). Conclusions The prevalence of elderly Chinese people undergoing influenza vaccination remains suboptimal. The government can promote vaccination by educating the public about the advantages, by publicizing locations where vaccinations are available, and having nursing, other medical staff, family and friends encourage elderly people to be vaccinated. A high vaccination coverage rate must be ensured to achieve international goals.


558. Anti-SARS Humoral and Cellular Immunity Evoked by an Adenovirus Vector Expressing Spike Glycoprotein from SARS Coronavirus


title: Antiviral Innate Immunity: Introduction☆

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


title: Risk of Severe Acute Respiratory Syndrome–Associated Coronavirus Transmission Aboard Commercial Aircraft

text: BACKGROUND: Severe acute respiratory syndrome–associated coronavirus (SARS‐CoV) was introduced to the United States through air travel. Although the risk of SARS‐CoV transmission within aircraft cabins has been addressed by several studies, the magnitude of the risk remains unclear. METHODS: We attempted to contact all persons with working US telephone numbers aboard seven US‐bound flights carrying SARS patients. Consenting participants responded to a questionnaire, and a serum sample was collected at least 38 days after the flight and tested for SARS‐CoV‐associated antibodies. Participants reporting an illness compatible with SARS, with onset during the 2‐ to 10‐day incubation period, were considered suspect cases; positive serology was required for confirmed cases. RESULTS: Among 1,766 passengers and crew, 339 (19%) persons were contacted. Of these, 312 (92%) completed questionnaires, and blood was collected from 127 (37%). Serology was negative for all 127 participants, including three of four who met the clinical case criteria for SARS, and the fourth had a mild illness that lasted only 5 days. CONCLUSIONS: Transmission of SARS‐associated CoV was not observed, suggesting that the risk of transmission is not amplified aboard aircraft.


title: Diagnostic virologique des infections respiratoires(☆)()

text: More than 80% of the cases of respiratory infections in children are of viral origin. Viral culture has been the reference method for the diagnosis of viral respiratory infections for years, but there is now a tendency to replace viral culture by molecular biology techniques, notably real-time PCR-based assay, because of its excellent sensitivity and good feasibility. Currently in most laboratories, however, diagnosis of viral respiratory infections is still done using techniques based on detection of viral antigens, especially immunofluorescence assays. Rapid diagnostic tests for use outside of laboratories are now available on the open market, and even if their sensitivity remains lower than that of other techniques, it is likely that they will become widely used, especially in doctors' offices, in the near future. New methods for the diagnosis of viral infections based on DNA microarray technologies are currently under investigation and appear to very promising.


title: Diversity of coronavirus in bats from Eastern Thailand

text: BACKGROUND: Bats are reservoirs for a diverse range of coronaviruses (CoVs), including those closely related to human pathogens such as Severe Acute Respiratory Syndrome (SARS) CoV and Middle East Respiratory Syndrome CoV. There are approximately 139 bat species reported to date in Thailand, of which two are endemic species. Due to the zoonotic potential of CoVs, standardized surveillance efforts to characterize viral diversity in wildlife are imperative. FINDINGS: A total of 626 bats from 19 different bat species were individually sampled from 5 provinces in Eastern Thailand between 2008 and 2013 (84 fecal and 542 rectal swabs). Samples collected (either fresh feces or rectal swabs) were placed directly into RNA stabilization reagent, transported on ice within 24 hours and preserved at −80°C until further analysis. CoV RNA was detected in 47 specimens (7.6%), from 13 different bat species, using broadly reactive consensus PCR primers targeting the RNA-Dependent RNA Polymerase gene designed to detect all CoVs. Thirty seven alphacoronaviruses, nine lineage D betacoronaviruses, and one lineage B betacoronavirus (SARS-CoV related) were identified. Six new bat CoV reservoirs were identified in our study, namely Cynopterus sphinx, Taphozous melanopogon, Hipposideros lekaguli, Rhinolophus shameli, Scotophilus heathii and Megaderma lyra. CONCLUSIONS: CoVs from the same genetic lineage were found in different bat species roosting in similar or different locations. These data suggest that bat CoV lineages are not strictly concordant with their hosts. Our phylogenetic data indicates high diversity and a complex ecology of CoVs in bats sampled from specific areas in eastern regions of Thailand. Further characterization of additional CoV genes may be useful to better describe the CoV divergence.


title: Adoption of preventive measures during and after the 2009 influenza A (H1N1) virus pandemic peak in Spain

text: Abstract Objective This study describes the preventive measures adopted by the Spanish population towards 2009 influenza A (H1N1) virus and their associated factors. Method An anonymous computer-assisted telephone interview survey was conducted in Spain in December 2009 and February 2010. Respondents were asked about their perceptions of influenza A (H1N1) virus and the preventive measures adopted. Factors associated with the adoption of preventive measures were assessed by logistic regression analyses. Results Out of 4892 households approached, 1627 valid responses were obtained (response rate of 33.3%). The most commonly adopted preventive measures were respiratory hygiene and hand washing. Factors independently associated with the adoption of the preventive measures recommended by the Spanish Ministry of Health were female gender, higher educational level, size of municipality of residence >50,000 inhabitants, high perceived susceptibility to infection, high perceived effectiveness of the measures and high perceived usefulness of the information provided by the government. The presence of school-aged children in household was associated with purchasing masks and hand sanitizer. Conclusion In addition to demographic factors, modifiable factors such as personal beliefs and expectations play a role in the adoption of preventive measures.


17 Health constraints on the agricultural recycling of wastewater sludges


COVID19 - The need for Public Health in a time of emergency


title: Prediction of severe illness due to COVID-19 based on an analysis of initial Fibrinogen to Albumin Ratio and Platelet count

text: Concomitant coagulation disorder can occur in severe patients withCOVID-19, but in-depth studies are limited. This study aimed to describe the parameters of coagulation function of patients with COVID-19 and reveal the risk factors of developing severe disease. This study retrospectively analyzed 113patients with SARS-CoV-2 infection in Taizhou Public Health Center. Clinical characteristics and indexes of coagulation function were collected. A multivariate Cox analysis was performed to identify potential biomarkers for predicting disease progression. Based on the results of multivariate Cox analysis, a Nomogram was built and the predictive accuracy was evaluated through the calibration curve, decision curve, clinical impact curve, and Kaplan–Meier analysis. Sensitivity, specificity, predictive values were calculated to assess the clinical value. The data showed that Fibrinogen, FAR, and D-dimer were higher in the severe patients, while PLTcount, Alb were much lower. Multivariate Cox analysis revealed that FAR and PLT count were independent risk factors for disease progression. The optimal cutoff values for FAR and PLT count were 0.0883 and 135*10(9)/L, respectively. The C-index [0.712 (95% CI = 0.610–0.814)], decision curve, clinical impact curve showed that Nomogram could be used to predict the disease progression. In addition, the Kaplan–Meier analysis revealed that potential risk decreased in patients with FAR<0.0883 and PLT count>135*10(9)/L.The model showed a good negative predictive value [(0.9474 (95%CI = 0.845–0.986)].This study revealed that FAR and PLT count were independent risk factors for severe illness and the severity of COVID-19 might be excluded when FAR<0.0883 and PLT count>135*10(9)/L.


title: Wheat and chaffs in the interpretation of the current COVID19 outbreak in Italy

text: The COVID19 outbreak in Italy is still a big concern. The Italian Government has recommended citizens to respect faithfully any compulsory legal disposition in order to stay home and so contributing in escaping viral contacts and slowing down epidemic. Emergency has raised a widely animated debate about how to read and comprehend the daily case numbers, the medical and caregivers availability, the needs to swab asymptomatic subjects. In this review the authors discuss about the many wheat and chaffs of how this virus disease is addressed .


title: Limited adaptation of chimeric H9N2 viruses containing internal genes from bat influenza viruses in chickens

text: Abstract Influenza virus-like sequences of H17N10 and H18N11 were identified in bats, despite there has been no live virus isolated. The genetic analysis indicated that they have distinct but relatively close evolutionary relationships to known influenza A viruses. However, the infectivity and adaptation of bat influenza viruses in avian species remain unclear. In this study, two modified bat influenza viruses cH9cN2/H17 and cH9cN2/H18 containing HA and NA coding regions replaced with those of H9N2 influenza A virus were generated in the background of the H17N10 or H18N11 viruses. These two modified viruses replicated less efficiently than wild type H9N2 virus in cultured chicken cells. The mini-genome assay showed that viral ribonucleoproteins (vRNPs) of H9N2 has significantly higher polymerase activity than that of bat influenza viruses in avian cells. In chicken study, compared with H9N2 virus, which replicated and transmitted efficiently in chickens, the cH9cN2/H17 and cH9cN2/H18 viruses only replicated in chicken tracheas with lower titers. Pathological examination showed that the H9N2 caused severer lesions in lung and trachea than the modified bat influenza viruses. Notably, the cH9cN2/H18 transmitted among chickens, but not cH9cN2/H17, and chicken IFN-β antagonism results showed that H18N11 NS1 protein inhibited chicken IFN-β response more efficiently than H17N10 NS1 protein in avian cells. Taken together, our data indicated that the internal genes of bat influenza viruses adapted poorly to chickens, while the internal genes of H18N11 seemed to adapt to chickens better than H17N10.


title: A CpG oligodeoxynucleotide inducing anti-coxsackie B3 virus activity in human peripheral blood mononuclear cells

text: Coxsackie B3 virus (CVB3) is the most significant pathogen causing myocarditis in humans, and antiviral therapy would be most effective in the early stages of the disease. Here we provide evidence that BW001, a C-type CpG oligodeoxynucleotide, induces anti-CVB3 activity in human peripheral blood mononuclear cells (PBMCs). In parallel, we have demonstrated that BW001 induces human PBMCs to express mRNAs of multiple types of interferon (IFN), including IFN-α, IFN-β, IFN-ω and IFN-γ, and to express mRNAs of at least 11 subtypes of IFN-α. The induced IFNs may contribute to the anti-CVB3 activity. The results suggest that BW001 could be developed into a medication with the potential to treat CVB3 infectious diseases by inducing natural mixed IFNs.


title: Prevalence and Etiology of Community-acquired Pneumonia in Immunocompromised Patients

text: BACKGROUND: The correct management of immunocompromised patients with pneumonia is debated. We evaluated the prevalence, risk factors, and characteristics of immunocompromised patients coming from the community with pneumonia. METHODS: We conducted a secondary analysis of an international, multicenter study enrolling adult patients coming from the community with pneumonia and hospitalized in 222 hospitals in 54 countries worldwide. Risk factors for immunocompromise included AIDS, aplastic anemia, asplenia, hematological cancer, chemotherapy, neutropenia, biological drug use, lung transplantation, chronic steroid use, and solid tumor. RESULTS: At least 1 risk factor for immunocompromise was recorded in 18% of the 3702 patients enrolled. The prevalences of risk factors significantly differed across continents and countries, with chronic steroid use (45%), hematological cancer (25%), and chemotherapy (22%) the most common. Among immunocompromised patients, community-acquired pneumonia (CAP) pathogens were the most frequently identified, and prevalences did not differ from those in immunocompetent patients. Risk factors for immunocompromise were independently associated with neither Pseudomonas aeruginosa nor non–community-acquired bacteria. Specific risk factors were independently associated with fungal infections (odds ratio for AIDS and hematological cancer, 15.10 and 4.65, respectively; both P = .001), mycobacterial infections (AIDS; P = .006), and viral infections other than influenza (hematological cancer, 5.49; P < .001). CONCLUSIONS: Our findings could be considered by clinicians in prescribing empiric antibiotic therapy for CAP in immunocompromised patients. Patients with AIDS and hematological cancer admitted with CAP may have higher prevalences of fungi, mycobacteria, and noninfluenza viruses.


title: Influenza Infections and Emergent Viral Infections in Intensive Care Unit

text: Critically ill patients are admitted to an intensive care unit (ICU) for multiple reasons. In this study, we aim to analyze the current evidence and findings associated with influenza and other emergent viral infections, namely, herpes simplex virus type 1 (HSV-1), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). Among medical conditions, community-acquired respiratory infections are the most frequent reason for ventilatory support in ICUs. Community-acquired pneumonia in a severe form including the need of invasive mechanical ventilation and/or vasopressors is associated with high mortality rates. However, after the pandemic that occurred in 2009 by H1N1 influenza, the number of cases being admitted to ICUs with viral infections is on the rise. Patients in whom an etiology would not have been identified in the past are currently being tested with more sensitive viral molecular diagnostic tools, and patients being admitted to ICUs have more preexisting medical conditions that can predispose to viral infections. Viral infections can trigger the dysregulation of the immune system by inducing a massive cytokine response. This cytokine storm can cause endothelial damage and dysfunction, deregulation of coagulation, and, consequently, alteration of microvascular permeability, tissue edema, and shock. In severe influenza, this vascular hyperpermeability can lead to acute lung injury, multiorgan failure, and encephalopathy. In immunocompetent patients, the most common viral infections are respiratory, and influenza should be considered in patients with severe respiratory failure being admitted to ICU. Seasonality and coinfection are two important features when considering influenza as a pathogen in critically ill patients. Herpesviridae (HSV, CMV, and EBV) may reactivate in ICU patients, and their reactivation is associated with morbidity/mortality. However, whether a specific treatment may impact on outcome remains to be determined.


title: Electron microscopy of the intestine of gnotobiotic piglets infected with porcine rotavirus

text: Abstract Five gnotobiotic piglets inoculated orally with porcine rotavirus developed an enteric lesion. Electron microscopy of the mucosal epithelium 12 h after inoculation showed that the virus penetrates into the absorptive cells between microvilli, possibly by a pinocytic mechanism. Afterwards, virus particles were most often seen within dilated cisternae of the rough endoplasmic reticulum (RER). These infected cells showed a range of changes, such as disruption of the microvilli, loss of cytoplasmic density and deposition of lipid droplets. Subsequently, most of the epithelial cells were desquamated from the villi. The interaction of virus and intestinal cells thus indicates that rotavirus is pathogenic for the epithelial cells.


Cervicofacial nocardiosis in children


title: Differential Sensitivity of Bat Cells to Infection by Enveloped RNA Viruses: Coronaviruses, Paramyxoviruses, Filoviruses, and Influenza Viruses

text: Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.


title: Pandemic Best Regulatory Practices: An Urgent Need in the Covid‐19 Pandemic

text: As large numbers of candidate drugs and vaccines for potential use in the Covid‐19 pandemic are investigated, medicines regulators globally must now make urgent, informed, contextually risk‐based decisions regarding clinical trials and marketing authorizations. They must do this with the flexibility demanded by the pandemic while maintaining their core risk assessment and public safety functions. We lay out the critical role of regulators in the current crisis and offer eight “pandemic best regulatory practices.”


title: Comprehensive quantitative analysis of Shuang-Huang-Lian oral liquid using UHPLC–Q-TOF-MS and HPLC-ELSD

text: Abstract Shuang-Huang-Lian oral liquid (SHL) is a well-known Chinese patent drug containing three herbal medicines: Radix Scutellariae, Flos Lonicerae Japonicae and Fructus Forsythiae. It is usually used to treat acute upper respiratory tract infection caused by virus or bacteria. Although the licensing of botanical drug Veregen approved by FDA has indicated the importance of quantitative analysis in quality control of herbal medicines, quantitative evaluation of a Chinese patent drug like SHL remains a challenge due to the complex chemical profile. In this study, 15 small molecular components of SHL (four flavonoids, six quinic acid derivatives, three saponins and two phenylethanoid glycosides) were simultaneously determined using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC–Q-TOF-MS). The contents of the three major saccharides, namely fructose, glucose and sucrose were quantified using high performance liquid chromatography-evaporative light scattering detector on an amino column (HPLC-ELSD). The macromolecules were quantified by precipitating in 80% ethanol, drying the precipitate, and then weighing. The established methods were validated in terms of linearity, sensitivity, precision, accuracy and stability and then successfully applied to analyze 12 batches of commercial products of SHL produced by four different manufacturers. The results indicated that 57.52–78.11% (w/w) of SHL could be quantitatively determined (non-saccharide small molecules: 1.77–3.75%, monosaccharides: 0.93–20.93%, macromolecules: 2.63–5.76% and sucrose: 49.20–65.94%). This study may provide a useful way to comprehensively evaluate the quality of SHL.


title: Resilience of local food systems and links to food security – A review of some important concepts in the context of COVID-19 and other shocks

text: The objective of this review is to explore and discuss the concept of local food system resilience in light of the disruptions brought to those systems by the 2020 COVID-19 pandemic. The discussion, which focuses on low and middle income countries, considers also the other shocks and stressors that generally affect local food systems and their actors in those countries (weather-related, economic, political or social disturbances). The review of existing (mainly grey or media-based) accounts on COVID-19 suggests that, with the exception of those who lost members of their family to the virus, as per June 2020 the main impact of the pandemic derives mainly from the lockdown and mobility restrictions imposed by national/local governments, and the consequence that the subsequent loss of income and purchasing power has on people’s food security, in particular the poor. The paper then uses the most prominent advances made recently in the literature on household resilience in the context of food security and humanitarian crises to identify a series of lessons that can be used to improve our understanding of food system resilience and its link to food security in the context of the COVID-19 crisis and other shocks. Those lessons include principles about the measurement of food system resilience and suggestions about the types of interventions that could potentially strengthen the abilities of actors (including policy makers) to respond more appropriately to adverse events affecting food systems in the future.


title: Reconstructing and forecasting the COVID-19 epidemic in the United States using a 5-parameter logistic growth model

text: BACKGROUND: Many studies have modeled and predicted the spread of COVID-19 (coronavirus disease 2019) in the U.S. using data that begins with the first reported cases. However, the shortage of testing services to detect infected persons makes this approach subject to error due to its underdetection of early cases in the U.S. Our new approach overcomes this limitation and provides data supporting the public policy decisions intended to combat the spread of COVID-19 epidemic. METHODS: We used Centers for Disease Control and Prevention data documenting the daily new and cumulative cases of confirmed COVID-19 in the U.S. from January 22 to April 6, 2020, and reconstructed the epidemic using a 5-parameter logistic growth model. We fitted our model to data from a 2-week window (i.e., from March 21 to April 4, approximately one incubation period) during which large-scale testing was being conducted. With parameters obtained from this modeling, we reconstructed and predicted the growth of the epidemic and evaluated the extent and potential effects of underdetection. RESULTS: The data fit the model satisfactorily. The estimated daily growth rate was 16.8% overall with 95% CI: [15.95, 17.76%], suggesting a doubling period of 4 days. Based on the modeling result, the tipping point at which new cases will begin to decline will be on April 7th, 2020, with a peak of 32,860 new cases on that day. By the end of the epidemic, at least 792,548 (95% CI: [789,162, 795,934]) will be infected in the U.S. Based on our model, a total of 12,029 cases were not detected between January 22 (when the first case was detected in the U.S.) and April 4. CONCLUSIONS: Our findings demonstrate the utility of a 5-parameter logistic growth model with reliable data that comes from a specified period during which governmental interventions were appropriately implemented. Beyond informing public health decision-making, our model adds a tool for more faithfully capturing the spread of the COVID-19 epidemic.


title: Response to ‘all these D‐dimers in COVID‐19’

text: We appreciate the opportunity to respond to the letter from Dr Thachil[1], who provided an interesting physiological explanation for coagulation‐fibrinolysis balance shifts of the Broncho‐alveolar haemostasis during COVID‐19 infection, and speculated that the extravascular fibrinolysis would be a source of elevated D‐dimers.


title: COVID-19 Fatalities, Latitude, Sunlight, and Vitamin D

text: BACKGROUND: Since Vitamin D is known to be vital in regulating the immune system, and sunlight UV radiation exposure on the skin produces Vitamin D and UV intensity is highest nearest the equator, a study was done to examine the correlation between the latitude and COVID-19 fatality rates for countries. METHODS: Eighty-eight countries were selected based on their likelihood of providing reliable data. Using death rates/million for each country from the “worldometer” web site, a correlation analysis was done between death rates and a country's latitude. RESULTS: A highly significant, positive correlation was found between lower death rates and a country's proximity to the equator (Pearson r = .40 p<.0001, two-tailed t-test). The R squared of .16 means that 16% of the variation in death rates among nations is accounted for by the latitude of the country. Evidence is presented suggesting a direct correlation between sunlight exposure and reduced mortality. DISCUSSION: This study is the first to document a statistically significant correlation between a country's latitude and its COVID-19 mortality and is consistent with other research regarding latitude, Vitamin D deficiency, and COVID-19 fatalities. Limitations of this study are noted. CONCLUSION: Further research is needed to confirm the correlation between latitude and COVID-19 fatalities, and to determine the optimum amounts of safe sunlight exposure and/or vitamin D oral supplementation to reduce COVID-19 fatalities in populations that are at high risk for vitamin D deficiency.


title: Radiological and pulmonary function outcomes of children with SARS

text: We examined the radiological and pulmonary function outcomes of children affected with severe acute respiratory syndrome (SARS) at 6 months from diagnosis. Twenty‐one female and 26 male Chinese patients (median age, 13.6 years; interquartile range, 9.9–16.0) were studied. In each subject, high‐resolution computed tomography (HRCT) of the thorax and pulmonary function were assessed. All children were asymptomatic and had a normal clinical examination. Mild pulmonary abnormalities were detected on HRCT in 16 (34.0%) subjects, including residual ground‐glass opacification (n = 5), air trapping (n = 8), and a combination of ground‐glass changes and air trapping (n = 3). The need for oxygen supplementation (P = 0.02) and lymphopenia during the course of illness (P = 0.012) were significant risk factors in predicting abnormal HRCT. There were no significant lung function differences between those with and without HRCT abnormalities. Despite complete clinical resolution, a considerable proportion of children affected with SARS had abnormal HRCT findings at 6 months. These abnormalities were more prevalent in those with severe disease. It is important that careful follow‐up be carried out to assess the clinical significance and persistence of such abnormalities. Pediatr Pulmonol. 2004; 38:427–433. © 2004 Wiley‐Liss, Inc.


title: The role of C5a in acute lung injury induced by highly pathogenic viral infections

text: The complement system, an important part of innate immunity, plays a critical role in pathogen clearance. Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. In highly pathogenic virus-induced acute lung diseases, high levels of chemotactic and anaphylatoxic C5a were produced as a result of excessive complement activaiton. Overproduced C5a displays powerful biological activities in activation of phagocytic cells, generation of oxidants, and inflammatory sequelae named “cytokine storm”, and so on. Blockade of C5a signaling have been implicated in the treatment of ALI induced by highly pathogenic virus. Herein, we review the literature that links C5a and ALI, and review our understanding of the mechanisms by which C5a affects ALI during highly pathogenic viral infection. In particular, we discuss the potential of the blockade of C5a signaling to treat ALI induced by highly pathogenic viruses.


title: Agreement Among 4 Sampling Methods to Identify Respiratory Pathogens in Dairy Calves with Acute Bovine Respiratory Disease

text: BACKGROUND: Four sampling techniques commonly are used for antemortem identification of pathogens from cattle with bovine respiratory disease (BRD): the nasal swab (NS), guarded nasopharyngeal swab (NPS), bronchoalveolar lavage (BAL), and transtracheal wash (TTW). Agreement among these methods has not been well characterized. OBJECTIVE: To evaluate agreement among TTW and NS, NPS, or BAL for identification of viral and bacterial pathogens in dairy calves with BRD. ANIMALS: One hundred dairy calves with naturally acquired BRD. METHODS: Calves were sampled by all 4 methods. Viral agents were identified by real‐time RT‐PCR, bacteria were identified by aerobic culture, and Mycoplasma bovis (M. bovis) isolates were speciated by PCR. Agreement among TTW and NS, NPS, or BAL was evaluated by calculating the kappa statistic and percent positive agreement. McNemar's exact test was used to compare the proportions of positive results. RESULTS: Agreement among TTW and NS, TTW and NPS, and TTW and BAL, was very good for identification of P. multocida, M. haemolytica, and M. bovis. For bovine respiratory syncytial virus (BRSV), agreement with TTW was moderate for NS, good for NPS, and very good for BAL. For bovine coronavirus (BCV), agreement with TTW was moderate for NS and NPS, and good for BAL. McNemar's test was significant only for BCV, indicating that for this pathogen the proportion of positive results from NS and NPS could not be considered comparable to TTW. CONCLUSIONS AND CLINICAL IMPORTANCE: This study provides guidance for veterinarians selecting diagnostic tests for antemortem identification of pathogens associated with BRD.


title: Respiratory tract infections in the military environment

text: Abstract Military personnel fighting in contemporary battlefields as well as those participating in combat training are at risk of contracting respiratory infections. Epidemiological studies have demonstrated that soldiers deployed to the harsh environment have higher rates of newly reported respiratory symptoms than non-deployers. Acute respiratory diseases are the principle reason for outpatient treatment and hospitalization among military personnel, with an incidence exceeding that of the adult civilian population by up to three-fold. Adenoviruses, influenza A and B viruses, Streptococcus pneumoniae, Streptococcus pyogenes, coronaviruses and rhinoviruses have been identified as the main causes of acute respiratory infections among the military population. Although infective pathogens have been extensively studied, a significant proportion of illnesses (over 40%) have been due to unknown causative agents. Other health hazards, which can lead to respiratory illnesses among troops, are extreme air temperatures, desert dust, emissions from burn pits, industrial pollutants, and airborne contaminants originating from degraded soil. Limited diagnostic capabilities, especially inside the area of operations, make it difficult to accurately estimate the exact number of respiratory diseases in the military environment. The aim of the study was to discuss the occurrence of respiratory tract infections in army personnel, existing risk factors and preventive measures.


Improved Respirator for Protection Against Exposure to Airborne Viruses


title: Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD

text: Abstract Background Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity. Objectives To determine the extent and nature of bronchial mucosal inflammation following experimental rhinovirus (RV)-16-induced COPD exacerbations and its relationship to disease severity. Methods Bronchial mucosal inflammatory cell phenotypes were determined at pre-infection baseline and following experimental RV infection in 17 GOLD stage II COPD subjects and as controls, 20 smokers and 11 non-smokers, with normal lung function. No subject had a history of asthma/allergic rhinitis: all were negative for aero-allergen skin prick tests. Results RV-infection increased the numbers of bronchial mucosal eosinophils and neutrophils only in COPD and CD8+ T-lymphocytes in COPD and non-smokers. Monocytes/macrophages, CD4+ T- and CD20+ B-lymphocytes were increased in all subjects. At baseline, compared to non-smokers, COPD subjects and smokers had increased numbers of bronchial mucosal monocytes/macrophages and CD8+ T-lymphocytes but fewer numbers of CD4+ T- and CD20+ B-lymphocytes. The virus-induced inflammatory cells in COPD were positively associated with virus load, illness severity and reductions in lung function. Conclusion Experimental rhinovirus infection induces bronchial mucosal eosinophilia and neutrophilia only in COPD and monocytes/macrophages and lymphocytes in both COPD and control subjects. The virus-induced inflammatory cell phenotypes observed in COPD positively related to virus load, illness severity. Anti-viral/anti-inflammatory therapies could attenuate bronchial inflammation and ameliorate virus-induced COPD exacerbations.


title: Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization

text: Abstract Liposomes are widely utilized as a carrier to improve therapeutic efficacy of agents thanks to their merits of high loading capacity, targeting delivery, reliable protection of agents, good biocompatibility, versatile structure modification and adjustable characteristics, such as size, surface charge, membrane flexibility and the agent loading mode. In particular, in recent years, through modification with immunopotentiators and targeting molecules, and in combination with innovative immunization devices, liposomes are rapidly developed as a multifunctional vaccine adjuvant-delivery system (VADS) that has a high capability in inducing desired immunoresponses, as they can target immune cells and even cellular organelles, engender lysosome escape, and promote Ag cross-presentation, thus enormously enhancing vaccination efficacy. Moreover, after decades of development, several products developed on liposome VADS have already been authorized for clinical immunization and are showing great advantages over conventional vaccines. This article describes in depth some critical issues relevant to the development of liposomes as a VADS, including principles underlying immunization, physicochemical properties of liposomes as the immunity-influencing factors, functional material modification to enhance immunostimulatory functions, the state-of-the-art liposome VADSs, as well as the marketed vaccines based on a liposome VADS. Therefore, this article provides a comprehensive reference to the development of novel liposome vaccines.


title: New immunopathologic insights into multiple sclerosis

text: Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system. Although the immune system seems to play an important role in the pathogenesis of disease, target antigens are still uncertain and pathways leading to tissue destruction have not been fully elucidated. Recent studies have significantly contributed to a better understanding of the disease process and broadened our view on possible scenarios of disease initiation and progression. We review the role of the immune system for the manifestation and evolution of MS and discuss different pathogenetic concepts. We conclude with an outlook on future strategies to identify the cause of MS.


title: Interaction of aurintricarboxylic acid (ATA) with four nucleic acid binding proteins DNase I, RNase A, reverse transcriptase and Taq polymerase

text: In the investigation of interaction of aurintricarboxylic acid (ATA) with four biologically important proteins we observed inhibition of enzymatic activity of DNase I, RNase A, M-MLV reverse transcriptase and Taq polymerase by ATA in vitro assay. As the telomerase reverse transcriptase (TERT) is the main catalytic subunit of telomerase holoenzyme, we also monitored effect of ATA on telomerase activity in vivo and observed dose-dependent inhibition of telomerase activity in Chinese hamster V79 cells treated with ATA. Direct association of ATA with DNase I (K(d) = 9.019 μM)), RNase A (K(d) = 2.33 μM) reverse transcriptase (K(d) = 0.255 μM) and Taq polymerase (K(d) = 81.97 μM) was further shown by tryptophan fluorescence quenching studies. Such association altered the three-dimensional conformation of DNase I, RNase A and Taq polymerase as detected by circular dichroism. We propose ATA inhibits enzymatic activity of the four proteins through interfering with DNA or RNA binding to the respective proteins either competitively or allosterically, i.e. by perturbing three-dimensional structure of enzymes.


title: (18)F-FDG PET/CT findings of COVID-19: a series of four highly suspected cases

text: PURPOSE: The aim of this case series is to illustrate the (18)F-FDG PET/CT findings of patients with acute respiratory disease caused by COVID-19 in Wuhan, Hubei province of China. METHODS: We describe the (18)F-FDG PET/CT results from four patients who were admitted to the hospital with respiratory symptoms and fever between January 13 and January 20, 2020, when the COVID-19 outbreak was still unrecognized and the virus infectivity was unknown. A retrospective review of the patients’ medical history, clinical and laboratory data, as well as imaging findings strongly suggested a diagnosis of COVID-19. RESULTS: All patients had peripheral ground-glass opacities and/or lung consolidations in more than two pulmonary lobes. Lung lesions were characterized by a high (18)F-FDG uptake and there was evidence of lymph node involvement. Conversely, disseminated disease was absent, a finding suggesting that COVID-19 has pulmonary tropism. CONCLUSIONS: Although (18)F-FDG PET/CT cannot be routinely used in an emergency setting and is generally not recommended for infectious diseases, our pilot data shed light on the potential clinical utility of this imaging technique in the differential diagnosis of complex cases.


title: Comparative Anti-Infectious Bronchitis Virus (IBV) Activity of (-)-Pinene: Effect on Nucleocapsid (N) Protein

text: In the present study, anti-IBV (infectious bronchitis virus) activities of (-)-pinenes were studied by MTT assay, as well as docking and molecular dynamic (MD) simulations. The CC(50)values of (-)-α-pinene and (-)-β-pinene were above 10 mM. And the maximum noncytotoxic concentrations (TD(0)) of (-)-α-pinene and (-)-β-pinene were determined as 7.88 ± 0.06 and 6.09 ± 0.31 mM, respectively. The two compounds were found to inhibit IBV with an IC(50) of 0.98 ± 0.25 and 1.32 ± 0.11 mM. The MTT assay showed that the inhibitions of (-)-pinenes against IBV appear to occur moderately before entering the cell but are much stronger occur after penetration of the virus into the cell. Molecular simulations indicated that (-)-α-pinene and (-)-β-pinene specifically interact with the active site which is located at the N terminus of phosphorylated nucleocapsid (N) protein, with the former being more potent than the latter. The binding energies of them are −36.83 and −35.59 kcal mol(−1), respectively. Results presented here may suggest that (-)-α-pinene and (-)-β-pinene possess anti-IBV properties, and therefore are a potential source of anti-IBV ingredients for the pharmaceutical industry.


title: Ingestible sensors correlate closely with peripheral temperature measurements in febrile patients

text: Summary Backgrounds Reliable non-invasive methods for measuring body temperature are essential for the diagnosis and monitoring of infectious disease. Methods This study used Intraclass Correlation Coefficients (ICC) and the Bland- Altman plot to analyse the agreement between temperature measurements using an ingestible capsule sensor, a skin sensor and two non-invasive peripheral temperature measurements (axillary and infrared non-contact), collected from a population of febrile patient admitted for infectious disease. Results Of the 77 febrile patients screened, 26 patients were enrolled. The ICC between axillary temperature measurements (Taxi) vs. non-contact measurements (Tno-c) were 0.34 [−0.18; 0.63], 0.87 [0.55; 0.94] between Taxi vs. ingestible capsule measurements (Tcap) and 0.12 [−0.09; 0.37] between Taxi vs. Tetac. The mean difference between Taxi vs Tno-c was −1.18 °C with limits of agreement (LoA) from −2.96 to 0.58 °C. The mean difference between Taxi vs Tcap was 0.48 °C, with LoA from −0.60 to 1.56 °C. The mean difference between Taxi vs Tetac was −4.23 °C with LoA from −7.22 to −1.23 °C. Conclusions Ingestible capsule measurements are reliable enough to adequately estimate the core body temperature in clinical practice. Its non-invasiveness, and the real-time remote control offer new opportunities for future research into fever during infectious diseases.


title: Intranasally administered alpha/beta interferon prevents extension of mouse hepatitis virus, strain JHM, into the brains of BALB/cByJ mice

text: Summary Intranasally administered alpha/beta interferon blocked extension of the coronavirus, mouse hepatitis virus, strain JHM (MHV-JHM), from the nose to the brain of BALB/cByJ mice following intranasal inoculation with the virus. Two hundred units of alpha/beta interferon were administered intranasally to BALB/cByJ mice daily over a five day period. The mice were exposed intranasally to 103 median tissue culture infectious doses of MHV-JHM on the third day of interferon treatment. Two days after virus exposure, the proportion of mice with MHV in nasal turbinates was reduced from 10 of 10 in the untreated group to 7 of 10 in the interferon-treated group, and mean titers in virus-containing noses were lower in the interferon-treated group. Five days after virus exposure, the proportion of mice with infectious virus in the brain was significantly lower in the interferon-treated group (1 of 10 mice) than in the untreated group (10 of 10 mice). Systemic infection, as measured by presence and concentration of virus in the spleen, was not affected by intranasal interferon treatment. These results suggest that intranasally administered interferon protects against local extension of MHV-JHM from nose to brain, but not against dissemination of virus to other organs, such as the spleen.


title: Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region

text: Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.


title: Impact of lockdown measures implemented during the Covid-19 pandemic on the burden of trauma presentations to a regional emergency department in Kwa-Zulu Natal, South Africa

text: INTRODUCTION: The Covid-19 pandemic triggered unprecedented nationwide regulations aimed primarily at slowing the spread of the virus. The objective of this study was to describe the effect of these regulations on the number and severity of trauma presentations to a regional emergency department in Kwa-Zulu Natal. METHODS: A retrospective cohort study of the triage register at Edendale Hospital Emergency Department was conducted, comparing all trauma presentations in the month of April 2020 with those from the preceding two years. The number of patients, mechanism of trauma and severity of illness were recorded and compared. RESULTS: A 47% reduction in the number of trauma cases was recorded for April 2020. The proportion of severe cases did not change. The categories showing a major decrease were motor vehicle accidents, pedestrian vehicle accidents, assault and gunshot wounds. The incidence of dog bite wounds and burns remained unchanged. CONCLUSION: This study shows that the burden of trauma presenting to the emergency department was decreased in the month of April 2020 by the regulations implemented in response to the Covid-19 pandemic.


Managing through a crisis: Managerial implications for business-to-business firms


title: Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

text: Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R 2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R 2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.


title: Potential false-negative nucleic acid testing results for Severe Acute Respiratory Syndrome Coronavirus 2 from thermal inactivation of samples with low viral loads

text: BACKGROUND: Corona Virus Disease-2019 (COVID-19) has spread widely throughout the world since the end of 2019. Nucleic acid testing (NAT) has played an important role in patient diagnosis and management of COVID-19. In some circumstances, thermal inactivation at 56 °C has been recommended to inactivate Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) before NAT. However, this procedure could theoretically disrupt nucleic acid integrity of this single-stranded RNA virus and cause false negatives in real-time polymerase chain reaction (RT-PCR) tests. METHODS: We investigated whether thermal inactivation could affect the results of viral NAT. We examined the effects of thermal inactivation on the quantitative RT-PCR results of SARS-CoV-2 particularly with regard to the rates of false-negative results for specimens carrying low viral loads. We additionally investigated the effects of different specimen types, sample preservation times and a chemical inactivation approach on NAT. RESULTS: Our work showed increased Ct values in specimens from diagnosed COVID-19 patients in RT-PCR tests after thermal incubation. Moreover, about half of the weak-positive samples (7 of 15 samples, 46.7%) were RT-PCR negative after heat inactivation in at least one parallel testing. The use of guanidinium-based lysis for preservation of these specimens had a smaller impact on RT-PCR results with fewer false negatives (2 of 15 samples, 13.3%) and significantly less increase in Ct values than heat inactivation. CONCLUSION: Thermal inactivation adversely affected the efficiency of RT-PCR for SARS-CoV-2 detection. Given the limited applicability associated with chemical inactivators, other approaches to ensure the overall protection of laboratory personnel need consideration.


title: Exacerbation of experimental autoimmune encephalomyelitis in rodents infected with murine gammaherpesvirus‐68

text: Viral infections have long been suspected to play a role in the pathogenesis of multiple sclerosis. In the present study, two different rodent models of experimental autoimmune encephalomyelitis (EAE) were used to demonstrate the ability of murine gammaherpesvirus‐68 (γHV‐68) to exacerbate development of neurological symptoms. SJL mice received UV‐inactivated γHV‐68 or intranasalγHV‐68, followed by immunization against proteolipid‐protein peptide 139–151. Infected mice became moribund within 10 days post‐immunization, whereas mice exposed to UV‐inactivated γHV‐68 recovered. In the second model, Lewis rats were exposed to UV‐inactivated γHV‐68 or to γHV‐68, followed by passive transfer of encephalitogenic T lymphocytes specific for myelin basic protein. Consistently, infected rats had higher clinical scores, and this result was observed during acute or latent γHV‐68 infection. It is unlikely that this γHV‐68‐induced exacerbation was due to significant viral replication within the central nervous system since nested PCR, viral plaque assays, and infectious‐centers assays demonstrated no detectable virus in spinal cords or brains of infected rodents undergoing EAE. Taken together, these studies demonstrate increased clinical symptoms of EAE in rodents infected by a gammaherpesvirus that has a limited ability to invade the central nervous system.


title: Eicosanoids and Respiratory Viral Infection: Coordinators of Inflammation and Potential Therapeutic Targets

text: Viruses are frequent causes of respiratory infection, and viral respiratory infections are significant causes of hospitalization, morbidity, and sometimes mortality in a variety of patient populations. Lung inflammation induced by infection with common respiratory pathogens such as influenza and respiratory syncytial virus is accompanied by increased lung production of prostaglandins and leukotrienes, lipid mediators with a wide range of effects on host immune function. Deficiency or pharmacologic inhibition of prostaglandin and leukotriene production often results in a dampened inflammatory response to acute infection with a respiratory virus. These mediators may, therefore, serve as appealing therapeutic targets for disease caused by respiratory viral infection.


title: A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes

text: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in two genes, PKD1 and PKD2, which encode polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Earlier work has shown that PC1 and PC2 assemble into a polycystin complex implicated in kidney morphogenesis. PC2 also assembles into homomers of uncertain functional significance. However, little is known about the molecular mechanisms that direct polycystin complex assembly and specify its functions. We have identified a coiled coil in the C-terminus of PC2 that functions as a homodimerization domain essential for PC1 binding but not for its self-oligomerization. Dimerization-defective PC2 mutants were unable to reconstitute PC1/PC2 complexes either at the plasma membrane (PM) or at PM-endoplasmic reticulum (ER) junctions but could still function as ER Ca(2+)-release channels. Expression of dimerization-defective PC2 mutants in zebrafish resulted in a cystic phenotype but had lesser effects on organ laterality. We conclude that C-terminal dimerization of PC2 specifies the formation of polycystin complexes but not formation of ER-localized PC2 channels. Mutations that affect PC2 C-terminal homo- and heteromerization are the likely molecular basis of cyst formation in ADPKD.


title: Fexaramine as an entry blocker for feline caliciviruses

text: Abstract Feline calicivirus (FCV) is a small non-enveloped virus containing a single-stranded, positive-sense RNA genome of approximately 7.7 kb. FCV is a highly infectious pathogen of cats and typically causes moderate, self-limiting acute oral and upper respiratory tract diseases or chronic oral diseases. In addition, in recent years, virulent, systemic FCV (vs-FCV) strains causing severe systemic diseases with a high mortality rate of up to 67% have been reported in cats. Although FCV vaccines are commercially available, their efficacy is limited due to antigenic diversity of FCV strains and short duration of immunity. In this study, we identified fexaramine as a potent inhibitor of FCV including vs-FCV strains in cell culture and demonstrated that fexaramine is a entry blocker for FCV by using various experiments including time-of-addition studies, generation of resistant viruses in cell culture and the reverse genetics system. A fexaramine resistant FCV mutant has a single amino acid change in the P2 domain of VP1 (the major capsid), and the importance of this mutation for conferring resistance was confirmed using the reverse genetics system. A comparative analysis of viral resistance was also performed using a peptidyl inhibitor (NPI52) targeting FCV 3C-like protease. Finally, the effects of combination treatment of fexaramine and NPI52 against FCV replication and emergence of resistant viruses were investigated in cell culture.


Characteristics and prognosis of patients with inflammatory bowel disease during the SARS-CoV-2 pandemic in the Basque Country (Spain)


title: Antiviral effects of IFIT1 in human cytomegalovirus‐infected fetal astrocytes

text: The prominent feature of human cytomegalovirus (HCMV) is cell tropism specificity for human fetal nervous system, which leads to severe fetal nervous system damage especially in first‐trimester gestation. In this study, human astrocytes isolated from fetal brain were infected with HCMV AD169 and whole genome transcriptome profile was performed. The results showed that the gene expression of interferon stimulated genes (ISGs), chemokine and chemokine receptors were significantly up‐regulated (P < 0.01). The antiviral replication effects of IFIT1 (Interferon‐induced protein with tetratricopeptide repeats 1, Fc = 148.17) was investigated. Lentivirus with IFIT1 overexpression or knockdown was transduced into astrocytes, respectively. The viral mRNA, protein expression and HCMV titers were determined. The results showed that IE1, IE2, pp65, and viral titers were significantly decreased in IFIT1 overexpression group and enhanced in the knockdown group compared with control one (P < 0.01). Taken together, this study revealed IFIT1 played an important antiviral role in HCMV infected fetal astrocytes. The prominent feature of human cytomegalovirus (HCMV) is cellular tropism specificity for human fetal brain nervous system leading to severe fetal nervous damage especially in first‐trimester gestation. In this study, human astrocytes isolated from first‐trimester fetal brain were infected with HCMV AD169 and IFIT1 was studied for its antiviral replication effects. The results provided insights into the function of IFIT1 as a key factor in antiviral defense contributing to development of targeted therapeutics to fetal brain with HCMV infection. J. Med. Virol. 89:672–684, 2017. © 2016 Wiley Periodicals, Inc.


title: Could anti-CD20 therapy jeopardize the efficacy of a SARS-CoV-2 vaccine?

text: A vaccine against SARS-CoV-2 might represent the most promising approach to halt durably the current COVID-19 pandemic. We believe that anti-CD20 therapy may jeopardize the efficacy of such a vaccine. This is regrettable because patients receiving anti-CD20 therapy (i.e. those with hematologic malignancies or autoimmune disorders) are particularly at risk of severe COVID-19 and, as such, are the most in need of a vaccine. Here, we review the reasons why anti-CD20 therapy may abrogate or diminish the efficacy of a vaccine against SARS-CoV-2 and we draw physicians’ attention towards this potential risk so that it can be considered when evaluating the risk/benefit ratio of anti-CD20 therapy during the current pandemic.


The non-contact handheld cutaneous infra-red thermometer for fever screening during the COVID-19 global emergency


title: Erythropoietin Induced Hemoglobin Sub‐Unit Beta may Stimulate Innate Immune RNA Virus Pattern Recognition, Suppress Reactive Oxygen Species, Reduce ACE2 Viral Doorway Opening and Neutrophil Extracellular Traps against Covid‐19

text: Erythropoietin may stimulate innate immunity against RNA viruses, such as Covid‐19, through hemoglobin sub‐unit Beta acting on the retinoic acid inducible gene I (RIG‐1) and melanoma differentiation associated gene 5 (MDA5) viral pattern recognition receptors, causing interferon production and also maintains the vascular endothelium, a major target of SARS‐CoV‐2, possibly reducing thrombotic events which are becoming increasingly recognized complications of COVID19. This article is protected by copyright. All rights reserved.


title: Wind tunnel tests of inter-flat pollutant transmission characteristics in a rectangular multi-storey residential building, part B: Effect of source location

text: Abstract The pollutant behavior in and around a naturally ventilated building requires to be investigated quantitatively as the growing concern on air quality within the built environment. The objective of the present study is to further investigate the wind induced inter-flat pollutant transmission and cross contamination routes in typical buildings in Shanghai. In this paper, a set of experiments was carried out in a boundary layer wind tunnel using a 1:30 reduced scale model that represented the typical configuration of rectangular multi-storey residential buildings. Sulfur hexafluoride (SF6) was employed as a tracer gas in the wind tunnel tests. Two natural ventilation modes, single-sided ventilation and cross ventilation were considered. The conditions under prevailing wind direction with different source locations on the windward side were compared. The pressure coefficients on all of the building façades and tracer gas concentration distributions were monitored and analysed. The experimental results elucidated that contaminant released from windward units could spread vertically and horizontally to other units on the source façade and downstream units. The source location was a significant influence factor on the pollutant concentration in various units. In the single-sided ventilated building, the infected risks of leeward units were even higher than those in some windward units. In the cross ventilated building, the vertical transmission could be suppressed and the horizontal transmission was reinforced. The study is helpful for further understanding of the inter-flat airborne transmission within an isolated building.


Viral Upper Respiratory Tract Infection and Otitis Media Complication in Young Children


title: Chilblains in children in the setting of COVID‐19 pandemic

text: BACKGROUND: Different skin manifestations of COVID‐19 are being reported. Acral lesions on the hands and feet, closely resembling chilblains, have been recognized during the peak incidence of the COVID‐19 pandemic. MATERIAL AND METHODS: A retrospective review of 22 children and adolescents with chilblain‐like lesions seen over a short period of time in the Emergency Department of a children's hospital during the peak incidence of COVID‐19 in Madrid, Spain. RESULTS: All patients had lesions clinically consistent with chilblains of the toes or feet, with three also having lesions of the fingers. Pruritus and mild pain were the only skin symptoms elicited, and only 10 had mild respiratory and/or GI symptoms. None had fever. Coagulation tests, hemogram, serum chemistry, and lupus anticoagulant were normal in all patients tested. One out of 16 tested cases had elevated D‐dimer results, but without systemic symptoms or other laboratory anomalies. SARS‐CoV‐2 PCR tested in 19 cases was positive in just one case. Skin biopsies obtained in six patients were consistent with chilblains. On follow‐up, all cases showed spontaneous marked improvement or complete healing. CONCLUSION: Acute chilblains were observed during COVID‐19 pandemic in children and teenagers. It is a mildly symptomatic condition with an excellent prognosis, usually requiring no therapy. Etiopathogenesis remains unknown.


title: Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

text: We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers.


title: Lessons learnt from COVID 19: An Italian multicentric epidemiological study of orthopaedic and trauma services

text: INTRODUCTION: The Pandemic caused by the SARS-CoV-2 has put a strain on the most of health systems all over the world. Many hospitals had to re-organize to deal with the emergency, so that the non-core activities have been suspended or cancelled, raising management problems. The aim of this multicentre study is to report the epidemiological orthopaedic and traumatological data between COVID and pre-COVID era and to analyse patients’ needs and their management. METHODS: We reported and compared traumatological and elective orthopaedic surgeries performed in three of the main hospital centres in Tuscany during COVID (March 2020) and pre-COVID (March 2019) era. We also reported the epidemiological data about the number of orthopaedic first aid visits at the main hub, analysing the main differences. For each centre, we reported the number, diagnosis, co-morbidities, treatment, hospital course, complications and outcomes of confirmed COVID 19 patients. We also indicated what kind of PPE were used by medical staff and patients at any visit. RESULTS: The scheduled surgery drastically decreased in all the centres and the most of procedures were carried out for tumours, infections and implant mobilizations during the COVID time, delaying all the other ones. Trauma activities slightly decreased between the two time points: proximal femur fractures continued to engage our hospitals at the same pre-COVID volumes, while minor traumas drastically decreased. We report a decrease of 70.95% in orthopaedic first aid, with first-aid-visits/hospitalization ratio of 14.3 in the pre-COVID time vs 6.3 in the COVID time. A total of 5 confirmed COVID patients were treated for fractures and 4 of them healed without complications. We report just one case of death among COVID patients. All the medical staff members have worn the PPE and no one have developed COVID symptoms. CONCLUSIONS: The COVID-19 raised many important issues, such as the optimal management of patients requiring the treatment of conventional diseases during a pandemic. The flow of patients changes from one area to another during a pandemic and an integrated approach within the same geographical area could be useful to better allocate resources and manage the patients’ needs. The preventive measures put in place in our country seem to work, but this first experience with COVID-19 crisis highlighted the chronic problems of our health system and we believe that we have to “learn the lesson” to be better prepared in the future.


title: CRISPR in livestock: From editing to printing

text: Precise genome editing of large animals applied to livestock and biomedicine is nowadays possible since the CRISPR revolution. This review summarizes the latest advances and the main technical issues that determine the success of this technology. The pathway from editing to printing, from engineering the genome to achieving the desired animals, does not always imply an easy, fast and safe journey. When applied in large animals, CRISPR involves time- and cost-consuming projects, and it is mandatory not only to choose the best approach for genome editing, but also for embryo production, zygote microinjection or electroporation, cryopreservation and embryo transfer. The main technical refinements and most frequent questions to improve this disruptive biotechnology in large animals are presented. In addition, we discuss some CRISPR applications to enhance livestock production in the context of a growing global demand of food, in terms of increasing efficiency, reducing the impact of farming on the environment, enhancing pest control, animal welfare and health. The challenge is no longer technical. Controversies and consensus, opportunities and threats, benefits and risks, ethics and science should be reconsidered to enter into the CRISPR era.


Spine surgery in Atlantic Canada in COVID-19 era: lessons learned so far.


title: Biodistribution of DNA Plasmid Vaccines against HIV-1, Ebola, Severe Acute Respiratory Syndrome, or West Nile Virus Is Similar, without Integration, despite Differing Plasmid Backbones or Gene Inserts

text: The Vaccine Research Center has developed a number of vaccine candidates for different diseases/infectious agents (HIV-1, Severe Acute Respiratory Syndrome virus, West Nile virus, and Ebola virus, plus a plasmid cytokine adjuvant—IL-2/Ig) based on a DNA plasmid vaccine platform. To support the clinical development of each of these vaccine candidates, preclinical studies have been performed in mice or rabbits to determine where in the body these plasmid vaccines would biodistribute and how rapidly they would clear. In the course of these studies, it has been observed that regardless of the gene insert (expressing the vaccine immunogen or cytokine adjuvant) and regardless of the promoter used to drive expression of the gene insert in the plasmid backbone, the plasmid vaccines do not biodistribute widely and remain essentially in the site of injection, in the muscle and overlying subcutis. Even though ∼ 10(14) molecules are inoculated in the studies in rabbits, by day 8 or 9(∼ 1 week postinoculation), already all but on the order of 10(4)−10(6) molecules per microgram of DNA extracted from tissue have been cleared at the injection site. Over the course of 2 months, the plasmid clears from the site of injection with only a small percentage of animals (generally 10−20%) retaining a small number of copies (generally around 100 copies) in the muscle at the injection site. This pattern of biodistribution (confined to the injection site) and clearance (within 2 months) is consistent regardless of differences in the promoter in the plasmid backbone or differences in the gene insert being expressed by the plasmid vaccine. In addition, integration has not been observed with plasmid vaccine candidates inoculated i.m. by Biojector 2000 or by needle and syringe. These data build on the repeated-dose toxicology studies performed (see companion article, Sheets et al., 2006) to demonstrate the safety and suitability for investigational human use of DNA plasmid vaccine candidates for a variety of infectious disease prevention indications.


title: Investigation on Flos Trollii: Constituents and bioactivities

text: Abstract Flos Trollii, the flowers of Trollius chinensis Bunge, has been widely used in Chinese and Mongolian medicine for its efficacy of heat-clearing and detoxification. This drug has both medicinal and edible applications, and has led to various pharmacognosy, natural product chemistry, and pharmacology studies. As a result, its chemical constituents and bioactivities have been well-characterized in recent years. Nevertheless, a couple of critical issues, such as the major effective components, are still unresolved. The present review summarizes research progress on this drug regarding the constituents and bioactivities based on investigations in these laboratories and the results reported in recent publications. In addition, the pending issues are discussed and constructive suggestions for further investigation are proposed.


title: Functional polymorphisms of the CCL2 and MBL genes cumulatively increase susceptibility to severe acute respiratory syndrome coronavirus infection

text: Summary Objectives To assess associations between the functional polymorphisms G-2518A at the chemokine (C–C motif) ligand 2 gene (CCL2) and mannose binding lectin (MBL) codon 54 variant (A/B) and susceptibility to SARS. Methods We genotyped the CCL2 G-2518A and MBL codon 54 variant (A/B) in 4 case–control populations of Chinese descent, totally consisting of 932 patients with SARS and 982 control subjects. Results Both the high-CCL2-producing GG genotype and the low-MBL-producing B allele were consistently associated with increased risks of SARS-CoV infection in all 4 case–control populations (joint P = 1.6 × 10−4 and 4.9 × 10−8, for CCL2 and MBL respectively), with no interaction between polymorphisms could be detected. Furthermore, all the 4 case–control studies demonstrated a cumulative effect on risk of SARS-CoV infection for the combination of polymorphisms (joint P = 1.3 × 10−10). However, tests using the area under the curve (AUC) indicated that at this stage, the polymorphisms were unlikely to be appropriate for risk prediction testing because of low AUC values (all <66%). Additionally, no association was observed between the polymorphisms and severity of SARS. Conclusions The CCL2 G-2518A and MBL codon 54 variant have a significantly cumulative effect on increased risk of SARS-CoV infection.


title: Canine parvovirus type 2c infection in a kitten associated with intracranial abscess and convulsions

text: A case of canine parvovirus type 2c (CPV-2c) infection in a 3-month-old feral kitten with a cerebral abscess and neurological disease is reported. The cat displayed ataxia and convulsions together with signs of gastroenteritis and profound alteration of the total and differential white blood cell counts. A parvovirus strain was detected by a TaqMan assay in the blood and faeces of the affected kitten, which was characterised as CPV by means of molecular assays but did not react with any of the CPV type-specific probes. By sequence and phylogenetic analyses of the VP2-protein gene, the CPV-2c strain displayed a non-coding mutation in the probe-binding region. Although the role of CPV-2c in this particular case is unclear, it is possible that it predisposed the kitten to the clinical signs seen. Continuous surveillance is needed to monitor future spreading of this CPV-2c mutant, and any associated clinical signs, in the dog and cat population.


title: The ACE2 expression in Sertoli cells and germ cells may cause male reproductive disorder after SARS‐CoV‐2 infection

text: The serious coronavirus disease‐2019 (COVID‐19) was first reported in December 2019 in Wuhan, China. COVID‐19 is an infectious disease caused by severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Angiotensin converting enzyme 2(ACE2) is the cellular receptor for SARS‐CoV‐2. Considering the critical roles of testicular cells for the transmission of genetic information between generations, we analyzed single‐cell RNA‐sequencing (scRNA‐seq) data of adult human testis. The mRNA expression of ACE2 was expressed in both germ cells and somatic cells. Moreover, the positive rate of ACE2 in testes of infertile men was higher than normal, which indicates that SARS‐CoV‐2 may cause reproductive disorders through pathway activated by ACE2 and the men with reproductive disorder may easily to be infected by SARS‐CoV‐2. The expression level of ACE2 was related to the age, and the mid‐aged with higher positive rate than young men testicular cells. Taken together, this research provides a biological background of the potential route for infection of SARS‐CoV‐2 and may enable rapid deciphering male‐related reproductive disorders induced by COVID‐19.


Exercise and Fitness in the age of social distancing during the COVID-19 Pandemic


title: Pharmacy practice in times of civil crisis: The experience of SARS and “the blackout” in Ontario, Canada

text: Abstract Background Crises affecting civilian infrastructure (including electricity supply, clean water, and access to institutional health services) may have an effect on the delivery of pharmacy services in the community. Objectives The objectives were to describe and analyze the impact of 2 major crises (the severe acute respiratory syndrome [SARS] outbreak, and the electrical system failure [“blackout”]) on pharmacy practice and pharmacists in Toronto, Canada. Methods An exploratory, qualitative study was undertaken. Pharmacists were recruited, provided informed consent, and were interviewed. Data from transcripts were coded and categorized to identify themes related to adaptive strategies undertaken by pharmacists during times of civil crisis. Results Five key themes emerged from this research: (1) during times of crisis, pharmacies become frontline health care facilities, (2) a vacuity of leadership/lack of utility of emergency preparedness guidelines and policies, (3) role of and reliance on experience and professional judgment, (4) importance of documentation, and (5) the importance of “teamness” in enabling successful adaptation during times of crisis. Conclusions Emergencies and civil crises will continue to occur. Findings of this study include the importance of effective documentation systems and teamwork practices, as well as confident reliance on professional judgment and experience, as determinants of successful adaptation to civil crises.


title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India

text: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on GISAID, a global initiative for sharing avian flu data. In this study, we have analysed the spike protein sequences from all five isolates and also compared their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and another at 1124 in the S2 domain of spike protein of the isolates from West Bengal only. There was one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of the mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.


title: Nrf2 protects human alveolar epithelial cells against injury induced by influenza A virus

text: BACKGROUND: Influenza A virus (IAV) infection primarily targets respiratory epithelial cells and produces clinical outcomes ranging from mild upper respiratory infection to severe pneumonia. Recent studies have shown the importance of lung antioxidant defense systems against injury by IAV. Nuclear factor-erythroid 2 related factor 2 (Nrf2) activates the majority of antioxidant genes. METHODS: Alveolar type II (ATII) cells and alveolar macrophages (AM) were isolated from human lungs not suitable for transplantation and donated for medical research. In some studies ATII cells were transdifferentiated to alveolar type I-like (ATI-like) cells. Alveolar epithelial cells were infected with A/PR/8/34 (PR8) virus. We analyzed PR8 virus production, influenza A nucleoprotein levels, ROS generation and expression of antiviral genes. Immunocytofluorescence was used to determine Nrf2 translocation and western blotting to detect Nrf2, HO-1 and caspase 1 and 3 cleavage. We also analyzed ingestion of PR8 virus infected apoptotic ATII cells by AM, cytokine levels by ELISA, glutathione levels, necrosis and apoptosis by TUNEL assay. Moreover, we determined the critical importance of Nrf2 using adenovirus Nrf2 (AdNrf2) or Nrf2 siRNA to overexpress or knockdown Nrf2, respectively. RESULTS: We found that IAV induced oxidative stress, cytotoxicity and apoptosis in ATI-like and ATII cells. We also found that AM can ingest PR8 virus-induced apoptotic ATII cells (efferocytosis) but not viable cells, whereas ATII cells did not ingest these apoptotic cells. PR8 virus increased ROS production, Nrf2, HO-1, Mx1 and OAS1 expression and Nrf2 translocation to the nucleus. Nrf2 knockdown with siRNA sensitized ATI-like cells and ATII cells to injury induced by IAV and overexpression of Nrf2 with AdNrf2 protected these cells. Furthermore, Nrf2 overexpression followed by infection with PR8 virus decreased virus replication, influenza A nucleoprotein expression, antiviral response and oxidative stress. However, AdNrf2 did not increase IFN-λ1 (IL-29) levels. CONCLUSIONS: Our results indicate that IAV induces alveolar epithelial injury and that Nrf2 protects these cells from the cytopathic effects of IAV likely by increasing the expression of antioxidant genes. Identifying the pathways involved in protecting cells from injury during influenza infection may be particularly important for developing new therapeutic strategies.


Irradiation pulmonaire à faible dose pour l’orage de cytokines du COVID-19 : pourquoi pas ?


title: Feasibility of a quantitative polymerase chain reaction assay for diagnosing pneumococcal pneumonia using oropharyngeal swabs

text: Streptococcus pneumoniae is the most important pathogen causing community-acquired pneumonia (CAP). The current diagnostic microbial standard detects S. pneumoniae in less than 30% of CAP cases. A quantitative polymerase chain reaction (PCR) targeting autolysin (lytA) is able to increase the rate of detection. The aim of this study is validation of this quantitative PCR in vitro using different available strains and in vivo using clinical samples (oropharyngeal swabs). The PCR autolysin (lytA) was validated by testing the intra- and inter-run variability. Also, the in vitro specificity and sensitivity, including the lower limit of detection was determined. In addition, a pilot-study was performed using samples from patients (n = 28) with pneumococcal pneumonia and patients (n = 28) with a pneumonia without detection of S. pneumoniae with the current diagnostic microbial standard, but with detection of either a viral and or another bacterial pathogen to validate this test further. The intra- and inter-run variability were relatively low (SD’s ranging from 0.08 to 0.96 cycle thresholds). The lower limit of detection turned out to be 1–10 DNA copies/reaction. In-vitro sensitivity and specificity of the tested specimens (8 strains carrying lytA and 6 strains negative for lytA) were both 100%. In patients with pneumococcal and non-pneumococcal pneumonia a cut-off value of 6.000 copies/mL would lead to a sensitivity of 57.1% and a specificity of 85.7%. We were able to develop a quantitative PCR targeting lytA with good in-vitro test characteristics. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11033-018-4558-0) contains supplementary material, which is available to authorized users.


title: IN VITRO ASSESSMENT OF THE BIOLOGIC ACTIVITY OF INTERFERON BETA FORMULATIONS USED FOR THE TREATMENT OF RELAPSING MULTIPLE SCLEROSIS

text: □ A new formulation (NF) of subcutaneous (sc) interferon (IFN) β-1a was developed in an attempt to improve injection tolerability and immunogenicity. We compared antiviral and IFNβ-stimulated gene (ISG) activities of IFNβ-1a sc NF with IFNβ-1a sc original formulation and IFNβ-1b sc. When equivalent unit amounts were compared, the IFNβ formulations demonstrated similar antiviral activity and induced similar levels of ISG mRNA. However, on a weight basis (ng/mL), significantly more IFNβ-1b sc was needed to equal the antiviral activity of either IFNβ-1a sc formulation, and both IFNβ-1a sc formulations induced significantly higher levels of ISG mRNA than IFNβ-1b sc.


title: Pharmacokinetics of a single inhalation of hydrogen gas in pigs

text: The benefits of inhaling hydrogen gas (H(2)) have been widely reported but its pharmacokinetics have not yet been sufficiently analyzed. We developed a new experimental system in pigs to closely evaluate the process by which H(2) is absorbed in the lungs, enters the bloodstream, and is distributed, metabolized, and excreted. We inserted and secured catheters into the carotid artery (CA), portal vein (PV), and supra-hepatic inferior vena cava (IVC) to allow repeated blood sampling and performed bilateral thoracotomy to collapse the lungs. Then, using a hydrogen-absorbing alloy canister, we filled the lungs to the maximum inspiratory level with 100% H(2). The pig was maintained for 30 seconds without resuming breathing, as if they were holding their breath. We collected blood from the three intravascular catheters after 0, 3, 10, 30, and 60 minutes and measured H(2) concentration by gas chromatography. H(2) concentration in the CA peaked immediately after breath holding; 3 min later, it dropped to 1/40 of the peak value. Peak H(2) concentrations in the PV and IVC were 40% and 14% of that in the CA, respectively. However, H(2) concentration decay in the PV and IVC (half-life: 310 s and 350 s, respectively) was slower than in the CA (half-life: 92 s). At 10 min, H(2) concentration was significantly higher in venous blood than in arterial blood. At 60 min, H(2) was detected in the portal blood at a concentration of 6.9–53 nL/mL higher than at steady state, and in the SVC 14–29 nL/mL higher than at steady state. In contrast, H(2) concentration in the CA decreased to steady state levels. This is the first report showing that inhaled H(2) is transported to the whole body by advection diffusion and metabolized dynamically.


title: On representing network heterogeneities in the incidence rate of simple epidemic models

text: Abstract Mean-field ecological models ignore space and other forms of contact structure. At the opposite extreme, high-dimensional models that are both individual-based and stochastic incorporate the distributed nature of ecological interactions. In between, moment approximations have been proposed that represent the effect of correlations on the dynamics of mean quantities. As an alternative closer to the typical temporal models used in ecology, we present here results on “modified mean-field equations” for infectious disease dynamics, in which only mean quantities are followed and the effect of heterogeneous mixing is incorporated implicitly. We specifically investigate the previously proposed empirical parameterization of heterogeneous mixing in which the bilinear incidence rate SI is replaced by a nonlinear term kS p I q , for the case of stochastic SIRS dynamics on different contact networks, from a regular lattice to a random structure via small-world configurations. We show that, for two distinct dynamical cases involving a stable equilibrium and a noisy endemic steady state, the modified mean-field model approximates successfully the steady state dynamics as well as the respective short and long transients of decaying cycles. This result demonstrates that early on in the transients an approximate power-law relationship is established between global (mean) quantities and the covariance structure in the network. The approach fails in the more complex case of persistent cycles observed within the narrow range of small-world configurations.


title: Transcriptional control of regulatory T cell development and function

text: Regulatory T (Treg) cells differentiate from thymocytes or peripheral T cells in response to host and environmental cues, culminating in induction of the transcription factor forkhead box P3 (Foxp3) and the Treg cell-specific epigenome. An intermediate amount of antigen stimulation is required to induce Foxp3 expression by engaging T cell receptor (TCR)-activated [e.g., nuclear factor (NF)-κB] and TCR-inhibited (e.g., Foxo) transcription factors. Furthermore, Treg cell differentiation is associated with attenuated Akt signaling, resulting in enhanced nuclear retention of Foxo1, which is indispensable for Treg cell function. These findings reveal that Treg cell lineage commitment is not only controlled by genetic and epigenetic imprinting, but also modulated by transcriptional programs responding to extracellular signals.


title: Geographical spread of SARS in mainland China

text: Objectives To describe the spatiotemporal diffusion of the severe acute respiratory syndrome (SARS) epidemic in mainland China, and to analyse the spatial pattern of SARS transmission from the Beijing epicentre to its neighbouring areas. Methods Probable SARS cases occurring between November 2002 and May 2003 in mainland China were compiled from different sources and geo‐coded into a geographical information database based on onset location. Spatial analyses including kernel density estimation, and spatial statistical and tracking analyses were performed to characterise the spatiotemporal distribution of SARS cases based on onset location/date. SARS cases that got infected in Beijing but were reported in three provinces surrounding Beijing were mapped, and logistic regression using a ‘case–control’ design at the county level was performed to analyse the impact of travel‐related risk factors in the diffusion pattern. Results The SARS epidemic in mainland China spanned a large geographical extent but clustered in two areas: first in Guangdong Province, and about 3 months later in Beijing with its surrounding areas in Shanxi Province, Inner Mongolia Autonomic Region, Hebei Province and Tianjin. Counties in the neighbourhood of Beijing that were crossed by a national highway or inter‐provincial freeway showed the highest risk of acquiring SARS infections, even after correction for population density and medical staff density. Being intersected by a railway did not significantly associate with risk of SARS. Conclusions This study provides the first complete documentation of the spatial and temporal characteristics of the SARS epidemic in mainland China. Our analyses confirmed that SARS had benefited from national highways and inter‐provincial freeways for its spread from epicentres to neighbouring areas, whereas trains showed no significant association. This knowledge may be important for the control of re‐emerging SARS, or other future emerging human‐to‐human transmittable infections.


title: Surveillance on secular trends of incidence and mortality for device–associated infection in the intensive care unit setting at a tertiary medical center in Taiwan, 2000–2008: A retrospective observational study

text: BACKGROUND: Device–associated infection (DAI) plays an important part in nosocomial infection. Active surveillance and infection control are needed to disclose the specific situation in each hospital and to cope with this problem effectively. We examined the rates of DAI by antimicrobial-resistant pathogens, and 30–day and in–hospital mortality in the intensive care unit (ICU). METHODS: Prospective surveillance was conducted in a mixed medical and surgical ICU at a major teaching hospital from 2000 through 2008. Trend analysis was performed and logistic regression was used to assess prognostic factors of mortality. RESULTS: The overall rate of DAIs was 3.03 episodes per 1000 device–days. The most common DAI type was catheter–associated urinary tract infection (3.76 per 1000 urinary catheter–days). There was a decrease in DAI rates in 2005 and rates of ventilator–associated pneumonia (VAP, 3.18 per 1000 ventilator–days) have remained low since then (p < 0.001). The crude rates of 30–day (33.6%) and in–hospital (52.3%) mortality, as well as infection by antibiotic-resistant VAP pathogens also decreased. The most common antimicrobial-resistant pathogens were methicillin–resistant Staphylococcus aureus (94.9%) and imipenem–resistant Acinetobacter baumannii (p < 0.001), which also increased at the most rapid rate. The rate of antimicrobial resistance among Enterobacteriaceae also increased significantly (p < 0.05). After controlling for potentially confounding factors, the DAI was an independent prognostic factor for both 30–day mortality (OR 2.51, 95% confidence interval [CI] 1.99–3.17, p = 0.001) and in–hospital mortality (OR 3.61, 95% CI 2.10–3.25, p < 0.001). CONCLUSIONS: The decrease in the rate of DAI and infection by resistant bacteria on the impact of severe acute respiratory syndrome can be attributed to active infection control and improved adherence after 2003.


title: Toward resilient food systems through increased agricultural diversity and local sourcing in the Carolinas

text: Biological and agricultural diversity are connected to food security through strengthened resilience to both anthropogenic and natural perturbations. Increased resilience to stress via increased biodiversity has been described in a number of natural systems. Diversity in food production can be considered on the following three levels: (a) genetic diversity as reflected in the range of cultivars which can be selected for production; (b) species diversity, captured through production of a wide range of crops on each farm; and (c) broad ecosystem diversity, described by the diversity of production between farms and within the broader food system. A network of locally based food producers and entrepreneurs provides opportunity for high diversity at each network stage, with increased adaptive capacity and the ability for rapid response to disturbance. We argue that production techniques that use carefully planned diverse plantings, such as biointensive cultivation, increase resilience by increased water use efficiency, yield and nutrient retention while reducing pressure from pests and pathogens. We present a model for a diverse, distributed food system in the North Carolina Piedmont and analyze an existing distributed network by a food hub in South Carolina. Through these models, we argue that a shift in the food network has the potential to increase local food security by having food more reliably available where it is needed and by contributing to local resilience through community economic development. The shift in food production and distribution systems serves multiple goals: When crop loss occurs, other crops still contribute to overall harvest, reducing net loss. Diverse on-farm production can support a more distributed network of food aggregators, processors, and markets than the current approach of large-scale consolidation. Finally, a distributed food supply network supported with diverse agricultural products can increase resilience by providing access to diversified markets for producers and improved food access to consumers with more food choices, while expanding the need for skilled jobs supporting the regionally based food industry.