title: Infectious and immunogenetic factors in bipolar disorder

text: OBJECTIVE: Despite the evidence supporting the association between infection and bipolar disorder (BD), the genetic vulnerability that mediates its effects has yet to be clarified. A genetic origin for the immune imbalance observed in BD, possibly involved in the mechanisms of pathogen escape, has, however, been suggested in recent studies. METHOD: Here, we present a critical review based on a systematic literature search of articles published until December 2016 on the association between BD and infectious/immunogenetic factors. RESULTS: We provide evidence suggesting that infectious insults could act as triggers of maladaptive immune responses in BD and that immunogenetic vulnerability may amplify the effects of such environmental risk factors, increasing susceptibility to subsequent environmental encounters. Quality of evidence was generally impaired by scarce attempt of replication, small sample sizes and lack of high‐quality environmental measures. CONCLUSION: Infection has emerged as a potential preventable cause of morbidity in BD, urging the need to better investigate components of the host–pathogen interaction in patients and at‐risk subjects, and thus opening the way to novel therapeutic opportunities.


OUT-OF-HOSPITAL CARDIAC ARREST AND DONATION AFTER CIRCULATORY DEATH DURING THE COVID-19 PANDEMIA


Covid-19 — The Search for Effective Therapy


title: Purified coronavirus Spike protein nanoparticles induce coronavirus neutralizing antibodies in mice

text: Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of the emergence of these viruses and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice.


title: Age and Ebola viral load correlate with mortality and survival time in 288 Ebola virus disease patients

text: Summary Background A Chinese medical team managed Ebola virus disease (EVD) patients in Sierra Leone from October 2014 to March 2015 and attended to 693 suspected patients, of whom 288 had confirmed disease. Methods A retrospective study was conducted of the 288 patients with confirmed disease. Clinical symptoms, manifestations, and serum viral load were analyzed and compared among the different groups for mortality and survival time. Results Among the 288 confirmed EVD patients (149 male and 139 female, median age 28 years, and median log viral load 6.68), 98 died, 36 recovered, and 154 were lost to follow-up. Common symptoms were fever (77.78%), fatigue (64.93%), abdominal pain (64.58%), headache (62.85%), and diarrhea (61.81%). Compared to patients aged<18 years, those who were older than 40 years had a higher probability of death (odds ratio 2.855, p =0.044). Patients with a viral load of >106 copies/ml had a higher case fatality rate than those with <106 copies/ml (odds ratio 3.095, p =0.004). Cox regression showed that age, viral load, and the presence of diarrhea correlated with mortality. Conclusion Patients with a high viral load, of older age, and with diarrhea had a higher mortality and shorter survival time.


title: Wait-time for hysterectomy and survival of women with early-stage cervical cancer: A clinical implication during the coronavirus pandemic

text: OBJECTIVE: A global pandemic caused by a novel coronavirus (Covid-19) has created unique challenges to providing timely care for cancer patients. In early-stage cervical cancer, postponing hysterectomy for 6–8 weeks is suggested as a possible option in the Covid-19 burdened hospitals. Yet, literature examining the impact of surgery wait-time on survival in early-stage cervical cancer remains scarce. This study examined the association between surgery wait-time of 8 weeks and oncologic outcome in women with early-stage cervical cancer. METHODS: This is a single institution retrospective observational study at a tertiary referral medical center examining women who underwent primary hysterectomy or trachelectomy for clinical stage IA-IIA invasive cervical cancer between 2000 and 2017 (N = 217). Wait-time from the diagnosis of invasive cervical cancer via biopsy to definitive surgery was categorized as: short wait-time (<8 weeks; n = 110) versus long wait-time (≥8 weeks; n = 107). Propensity score inverse probability of treatment weighting was used to balance the measured demographics between the two groups, and disease-free survival (DFS) and overall survival (OS) were assessed. A systematic literature review with meta-analysis was additionally performed. RESULTS: In a weighted model (median follow-up, 4.6 years), women in the long wait-time group had DFS (4.5-year rates, 91.2% versus 90.7%, hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.47–2.59, P = 0.818) and OS (95.0% versus 97.4%, HR 1.47, 95%CI 0.50–4.31, P = 0.487) similar to those in the short wait-time group. Three studies were examined for meta-analysis, and a pooled HR for surgery wait-time of ≥8 weeks on DFS was 0.96 (95%CI 0.59–1.55). CONCLUSION: Our study suggests that wait-time of 8 weeks for hysterectomy may not be associated with short-term disease recurrence in women with early-stage cervical cancer.


title: Models of infection and exacerbations in COPD

text: Despite optimal use of currently available therapy for stable COPD, acute exacerbations are common events that constitute a major health burden. The development of highly sensitive diagnostic tools highlighted the role of viral infections in inducing COPD exacerbations, with rhinoviruses being the most frequently identified virus type. So far, little is known about the mechanisms of virus-induced exacerbations. The recent development of the first human rhinovirus-induced COPD exacerbation model represents an invaluable tool towards increasing our knowledge of immunological and inflammatory mechanisms of COPD exacerbation. The model will give us the opportunity to highlight key inflammatory mediators representing possible therapeutic targets for the development of novel drugs able to treat and prevent acute episodes in COPD.


title: Readability of Online Patient Education Material for the Novel Coronavirus Disease (COVID-19): A Cross-sectional Health Literacy Study

text: Abstract Objectives The internet has become one of the most important resources for the general population when searching for health care information. However, the information available is not always suitable for all readers due to its difficult readability. We sought to assess the readability of online information regarding the novel Coronavirus disease (COVID-19) and establish whether they follow the patient educational information reading level recommendations. Study design This is a cross-sectional study. Methods We searched five key terms on Google and the first 30 results from each of the searches were considered for analysis. Five validated readability tests were utilized in order to establish the reading level for each article. Results Out of the 150 gathered articles, 61 met the inclusion criteria and were evaluated. None (0%) of the articles met the recommended 5th to 6th grade reading level (of a 11-12-year-old). The mean readability scores were: Flesch Reading Ease 44.14, Flesch-Kincaid Grade Level 12.04, Gunning-Fog Index 14.27, Simple Measure of Gobbledygook SMOG Index 10.71, and Coleman-Liau Index 12.69. Conclusions Online educational articles on COVID-19 provide information too difficult to read for the general population. The readability of articles regarding COVID-19 and other diseases needs to improve so that the general population may understand health information better and may respond adequately to protect themselves and limit the spread of infection.


title: Conservation of nucleotide sequences for molecular diagnosis of Middle East respiratory syndrome coronavirus, 2015

text: Summary Infection due to the Middle East respiratory syndrome coronavirus (MERS-CoV) is widespread. The present study was performed to assess the protocols used for the molecular diagnosis of MERS-CoV by analyzing the nucleotide sequences of viruses detected between 2012 and 2015, including sequences from the large outbreak in eastern Asia in 2015. Although the diagnostic protocols were established only 2 years ago, mismatches between the sequences of primers/probes and viruses were found for several of the assays. Such mismatches could lead to a lower sensitivity of the assay, thereby leading to false-negative diagnosis. A slight modification in the primer design is suggested. Protocols for the molecular diagnosis of viral infections should be reviewed regularly after they are established, particularly for viruses that pose a great threat to public health such as MERS-CoV.


title: Occurrence of canine parvovirus in dogs from Henan province of China in 2009–2014

text: BACKGROUND: There is no information concerning the genotype of Canine parvovirus (CPV) currently circulating in Henan province, China. Therefore, the aim of the present study was to provide insights into the epidemiology and molecular characterization of CPV circulating in Henan province from 2009 to 2014. RESULTS: Nineteen thousand nine hundred seven dogs from pet hospitals in the cities of Luoyang, Anyang, Jiaozuo, Sanmenxia, Xinxiang, Zhengzhou in Henan province between 2009 and 2014 were investigated. Over the 6-year period, 1169 CPV-positive cases were identified and the morbidity of CPV infection ranged from 4.16 to 8.06 %, although morbidity was not significant (P > 0.05) between 2009 and 2014. Factors associated with morbidity included sampling season, dog age, breed, vaccination status, and sex. CPV co-infection with coccidium (10.00 %), canine distemper virus (4.79 %), hookworm (2.40 %), canine coronavirus (1.11 %), roundworm (1.03 %), tapeworm (0.17 %) and Babesia spp. (0.09 %) were observed. The new CPV-2a variant was more prevalent than the new CPV-2b variant in Henan province. CPV 2c was not observed in this study. CONCLUSIONS: The epidemiology of CPV infection and identification of the circulating genotypes in Henan province, China from 2009 to 2014 determined that the new CPV-2a variant was more prevalent.


title: The Benefits of Transmission Dynamics Models in Understanding Emerging Infectious Diseases

text: Abstract Factors associated with the emergence and transmission of infectious diseases often do not follow the assumptions of traditional statistical models such as linearity and independence of outcomes. Transmission dynamics models are well suited to address infectious disease scenarios that do not conform to these assumptions. For example, these models easily account for changes in the incidence rates of infection as the proportions of susceptible and infectious persons change in the population. Fundamental concepts relating to these methods, such as the basic reproductive number, the effective reproductive number and the susceptible-infected-recovered compartmental models, are reviewed. In addition, comparisons and contrasts are made between the following concepts: microparasites and macroparasites, deterministic and stochastic models, difference and differential equations and homogeneous and heterogeneous mixing patterns. Finally, examples of how transmission dynamics models are being applied to factors associated with emerging infectious diseases, such as zoonotic origins, microbial adaption and change, human susceptibility and climate change, are reviewed.


title: Clinical Significance of Human Coronavirus in Bronchoalveolar Lavage Samples From Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

text: BACKGROUND. The possible role of human coronavirus (HCoV) in lower respiratory tract disease (LRTD) in hematopoietic cell transplant (HCT) recipients and patients with hematologic malignancies (HM) has not been well studied. METHODS. We conducted a retrospective review of HCT/HM patients with HCoV detected in bronchoalveolar lavage (BAL). HCoV strains were identified in BAL samples using strain-specific polymerase chain reaction. Mortality rates were compared among HCT recipients with LRTD caused by HCoV, respiratory syncytial virus (RSV), influenza virus, or parainfluenza virus (PIV) by multivariable Cox regression analysis. RESULTS. We identified 35 patients (37 episodes) with HCoV LRTD. Among 23 available BAL samples, 48% were strain OC43, 22% were NL63, 17% were 229E, and 13% were HKU1. Overall, 21 patients (60%) required oxygen therapy at diagnosis and 19 (54%) died within 90 days of diagnosis. Respiratory copathogens were detected in 21 episodes (57%), including viruses (n = 12), fungi (n = 10), and bacteria (n = 8). Mortality rates were not different between patients with and without copathogens (P = .65). In multivariable models, mortality associated with HCoV LRTD was similar to that seen with RSV, influenza, and PIV LRTD in HCT recipients (adjusted hazard ratio, 1.34 [95% confidence interval, .66–2.71], P = .41 vs RSV, adjusted for cell source, cytopenia, copathogens, oxygen use, and steroid use). CONCLUSIONS. HCoV LRTD in patients with HCT or HM is associated with high rates of oxygen use and mortality. Mortality associated with HCoV LRTD in HCT recipients appears to be similar to that seen with RSV, influenza virus, and PIV.


Evaluating Potential Deceased Donor Renal Transplant Recipients for Asymptomatic COVID-19


INFLUENCIA DE LA PANDEMIA POR SARS-COV-2 EN EL MANEJO DEL CÁNCER DE MAMA


title: Comparison of 3 Infrared Thermal Detection Systems and Self-Report for Mass Fever Screening

text: Despite limited evidence regarding their utility, infrared thermal detection systems (ITDS) are increasingly being used for mass fever detection. We compared temperature measurements for 3 ITDS (FLIR ThermoVision A20M [FLIR Systems Inc., Boston, MA, USA], OptoTherm Thermoscreen [OptoTherm Thermal Imaging Systems and Infrared Cameras Inc., Sewickley, PA, USA], and Wahl Fever Alert Imager HSI2000S [Wahl Instruments Inc., Asheville, NC, USA]) with oral temperatures (>100°F = confirmed fever) and self-reported fever. Of 2,873 patients enrolled, 476 (16.6%) reported a fever, and 64 (2.2%) had a confirmed fever. Self-reported fever had a sensitivity of 75.0%, specificity 84.7%, and positive predictive value 10.1%. At optimal cutoff values for detecting fever, temperature measurements by OptoTherm and FLIR had greater sensitivity (91.0% and 90.0%, respectively) and specificity (86.0% and 80.0%, respectively) than did self-reports. Correlations between ITDS and oral temperatures were similar for OptoTherm (ρ = 0.43) and FLIR (ρ = 0.42) but significantly lower for Wahl (ρ = 0.14; p<0.001). When compared with oral temperatures, 2 systems (OptoTherm and FLIR) were reasonably accurate for detecting fever and predicted fever better than self-reports.


title: Personal protective equipment in health care: Can online infection control courses transfer knowledge and improve proper selection and use?

text: We used observational evaluation to assess the ability of an online learning course to effectively transfer knowledge on personal protective equipment (PPE) selection and removal. During orientations for new hospital staff, 117 participants applied either airborne, droplet, or contact precautions in mock scenarios. Postcourse, all 3 scenarios demonstrated improvement in PPE sequence scores (P = .001); moreover, hand hygiene also was more frequent during both donning and doffing of PPE (P < .001).


title: Teledermatology for acne during COVID‐19: high patients’ satisfaction in spite of the emergency

text: Acne is a chronic inflammatory skin disease affecting the 9.4% of global population. Although it usually occurs in adolescents aged from 15 to 24 years old, it is not uncommon to develop in adults either. Boys are more frequently affected, particularly with severe forms of the disease.An adequate and continuous treatment of the disease is required in order to reduce acne lesions, prevent permanent scarring and limit the duration of the disorder.


title: Disease Transmission and Networks ☆

text: Abstract While epidemiological models have traditionally assumed that diseases spread by the mass action principle, actual contact networks within social groups do not meet this assumption. Theoretical models have shown that disease dynamics could vary considerably under different types of contact networks, but these models face challenges in terms of their evaluation due to the difficulty of collecting empirical data. The honeybee colony with its elaborate social organization and large repertoire of diseases provides an ideal setting to explore how the structure of the contact network contributes to the transmission of a disease.


title: Changes in salivary analytes in canine parvovirus: A high-resolution quantitative proteomic study

text: Abstract The present study evaluated the changes in salivary proteome in parvoviral enteritis (PVE) in dogs through a high-throughput quantitative proteomic analysis. Saliva samples from healthy dogs and dogs with severe parvovirosis that survived or perished due to the disease were analysed and compared by Tandem Mass Tags (TMT) analysis. Proteomic analysis quantified 1516 peptides, and 287 (corresponding to 190 proteins) showed significantly different abundances between studied groups. Ten proteins were observed to change significantly between dogs that survived or perished due to PVE. Bioinformatics’ analysis revealed that saliva reflects the involvement of different pathways in PVE such as catalytic activity and binding, and indicates antimicrobial humoral response as a pathway with a major role in the development of the disease. These results indicate that saliva proteins reflect physiopathological changes that occur in PVE and could be a potential source of biomarkers for this disease.


Immunology and Gene Therapy: Shoulder to Shoulder Into the Fray International Symposium: Critical Frontiers Between Immunity and Gene Therapy Pamplona, Spain, 27–28 October 2009


title: 14 Main Microbiological Pollutants of Bottled Waters and Beverages

text: Abstract Although consumption of quality drinking water should be available to anyone, without any risk, in reality, for the people living in poor countries, safe water sources are often not an option. In order to eliminate the risk of disease, people prefer to use bottled water, or even bottle beverages, considering them uncontaminated, sterile products. However, the evidence showed that some microbial species belonging to autochthonous water microbiota or even pathogenic species may contaminate and could, in certain conditions, multiply beyond measure in the bottled products. Sometimes, although the bottled water or beverages meet the quality requirements, still, they could be responsible by some water- or food-borne diseases. This chapter presents the main microbial contaminants of these products and the associated risk for waterborne/food-borne diseases.


title: In vivo transmission studies of ‘Candidatus Mycoplasma turicensis’ in the domestic cat

text: The natural transmission routes of the three feline haemotropic mycoplasmas – Mycoplasma haemofelis, ‘Candidatus Mycoplasma haemominutum’, and ‘Candidatus Mycoplasma turicensis’ (CMt) – are largely unknown. Since CMt has been detected in the saliva of infected cats using PCR, we hypothesised that direct transmission via social or aggressive contact may occur. The aim of this study was to evaluate this transmission route. CMt-positive saliva and blood samples were obtained from three prednisolone-treated specific pathogen-free (SPF) cats that were infected intraperitoneally with CMt. Five SPF cats were inoculated with CMt-positive saliva or blood subcutaneously to mimic cat bites, and five cats were inoculated orally with blood or oronasally with saliva to mimic social contact. Blood samples were monitored for CMt infection using quantitative real-time PCR and for seroconversion using a novel western blot assay. Neither oronasal nor subcutaneous inoculation with CMt-positive saliva led to CMt infection in the recipient cats, as determined by PCR, independent of prior prednisolone treatment. However, when blood containing the same CMt dose was given subcutaneously, 4 of the 5 cats became PCR-positive, while none of the 5 cats inoculated orally with up to 500 μL of CMt-positive blood became PCR-positive. Subsequently, the latter cats were successfully subcutaneously infected with blood. All 13 CMt-exposed cats seroconverted. In conclusion, CMt transmission by social contact seems less likely than transmission by aggressive interaction. The latter transmission may occur if the recipient cat is exposed to blood from an infected cat.


title: Strategies in reconfiguration of hand injuries management during COVID-19 pandemic

text: During the COVID-19 pandemic there has been a re-organisation of care provided by the Trauma and Orthopaedic services in the United Kingdom. The National Health Service England (NHSE) speciality guide forms the primary responses to this pandemic, whilst British Society for the Surgery of Hand (BSSH) provides sub-specialty guidance on management of hand trauma. The orthopaedic community's responsibility of providing a continuity of care for patients has to be balanced with measures to reduce risk of viral transmission (e.g. reduce face to face consultations) and also protect ion of both the patients and staff. We highlight the strategies applied whilst reconfiguration of hand injury management following publication of COVID-19 British Society for the Surgery of Hand and Indian Orthopaedic Association (IOA) guidelines.


title: Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety

text: There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallised into stable microparticles (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallises as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cGMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while at the same time being safe and well tolerated. Advax™ adjuvant thereby represents a novel human adjuvant with positive effects on both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action.


title: Porcine reproductive and respiratory syndrome virus (PRRSv) interaction with Haemophilus parasuis

text: Abstract The interaction of bacteria and virus has been well demonstrated in the pathogenesis of respiratory disease in swine. The interaction between porcine respiratory and reproductive syndrome virus (PRRSv) and Haemophilus parasuis has not been studied. We initiated studies to evaluate a possible effect of the PRRSv on the pathogenesis of polyserositis caused by H. parasuis. A group of 30 three week old piglets were distributed in 4 groups. Group I (10 pigs) was inoculated with PRRSv and H. parasuis. Group II (10 pigs) was inoculated with H. parasuis alone. Group III (5 pigs) was inoculated with virus alone and group IV (5 pigs) was inoculated with culture media. Lesions consisted of a severe fibrinous polyserositis affecting 7 of 10 animals in group II and a mild fibrinous pleuritis in 1 of 10 animals of group I. Three of ten animals dually infected with the two agents died during the course of the study. These animals had pulmonary congestion and focal lung hemorrhages. No other animals died from other groups. Group III and IV had no macroscopic lesions. Microscopically group III had interstitial pneumonia. Immunomodulating virus effect may explain the differences in terms of lesions severity between groups I and II. Septic shock was suspected as cause of sudden death.


title: The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19

text: This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.


title: Review: The safe handling of a corpse (suspected) with COVID-19

text: INTRODUCTION: Countries around the world are confronted with a rising count of patients that die from COVID-19. Up to this date, there is no scientific evidence that proves that a COVID-19 corpse is still infectious. Different guidelines are being followed worldwide on how to deal with a COVID-19 positive corpse. The aim of this review is to compare different guidelines and literature on best practice for handling a COVID-19 positive corpse. RESULTS: The guidelines vary greatly in the use of PPE's and other safety measures especially during autopsy. There is great variation in the use of disinfectant and its concentration. Also recommended funeral services and contact with relatives vary greatly. CONCLUSION: In conclusion, there is very limited scientific evidence on which the researched guidelines are based. It is unclear why some guidelines propose a “business as usual” attitude and others a “code-red” attitude. More scientific evidence is needed to substantiate the handling of COVID-19 positive corpses to make an educated decision on how to safely handle a COVID-19 positive corpse.


title: The Collaborative Cross: A Systems Genetics Resource for Studying Host-Pathogen Interactions

text: Host genetic variation has a major impact on infectious disease susceptibility. The study of pathogen resistance genes, largely aided by mouse models, has significantly advanced our understanding of infectious disease pathogenesis. The Collaborative Cross (CC), a newly developed multi-parental mouse genetic reference population, serves as a tractable model system to study how pathogens interact with genetically diverse populations. In this review, we summarize progress utilizing the CC as a platform to develop improved models of pathogen-induced disease and to map polymorphic host response loci associated with variation in susceptibility to pathogens.


title: Prevalence of Newcastle disease virus and infectious bronchitis virus in avian influenza negative birds from live bird markets and backyard and commercial farms in Ivory-Coast

text: Abstract Newcastle disease (ND) and infectious bronchitis (IB) are two major viral diseases affecting the respiratory tracts of birds and whose impact on African poultry is still poorly known. In the present study we aimed at assessing NDV and IBV prevalences in Ivory-Coast by molecular screening of >22,000 avian swabs by nested PCR and by serology testing of close to 2000 avian sera from 2010 through 2012. The NDV and IBV seroprevalences over the study period reached 22% and 72%, respectively. We found 14.7% pooled swabs positive by PCR for NDV and 14.6% for IBV. Both pathogens are therefore endemic in Ivory-Coast. Economic losses associated with NDV and IBV infections still need to be evaluated.


title: Prevalence of intestinal parasites in companion dogs with diarrhea in Beijing, China, and genetic characteristics of Giardia and Cryptosporidium species

text: Companion animals including dogs are one of the important components in One Health. Parasites may cause not only diseases in pet animals but also many zoonotic diseases infecting humans. In this study, we performed a survey of intestinal parasites in fecal specimens (n = 485) collected from outpatient pet dogs with diarrhea in Beijing, China, for the entire year of 2015 by microscopic examination (all parasites) and SSU rRNA-based nested PCR detection (Giardia and Cryptosporidium). We observed a total of 124 (25.6%) parasite-positive specimens that contained one or more parasites, including Giardia duodenalis (12.8%), Cryptosporidium spp. (4.9%), Cystoisospora spp. (4.3%), trichomonads (4.3%), Toxocara canis (3.5%), Trichuris vulpis (0.6%), and Dipylidium caninum (0.2%). Among the 55 dog breeds, infection rates were significantly higher in border collies and bulldogs, but lower in poodles (p < 0.05). Risk factor analysis suggested that age was negatively correlated with the infection rate (p < 0.00001), while vaccination and deworming in the past 12 months could significantly reduce the parasite infections (p < 0.01). Among the 62 Giardia-positive specimens, 21 were successfully assigned into assemblages using glutamate dehydrogenase (gdh) and/or beta-giardin (bg) genes, including assemblage D (n = 15), C (n = 5), and F (n = 1). Among the 24 Cryptosporidium-positive specimens by SSU rRNA PCR, 20 PCR amplicons could be sequenced and identified as Cryptosporidium canis (n = 20). Collectively, this study indicates that parasites are a significant group of pathogens in companion dogs in Beijing, and companion dogs may potentially transmit certain zoonotic parasites to humans, particularly those with weak or weakened immunity.


title: Applications of enzyme-linked immunosorbent assay in veterinary medicine: A bibliography

text: During the last decade enzyme-linked immunosorbent assay has been a technique of major interest to those engaged in immunodiagnostics of human and animal diseases. Owing to its simplicity, specificity and sensitivity it has taken precedence over other conventional assays, including radioimmunoassay on the grounds of freedom from radiation hazards. Many applications of this assay have been developed in veterinary medicine and they are listed in this article.


title: Factors associated with negative conversion of viral RNA in patients hospitalized with COVID-19

text: Abstract Factors associated with negative conversion of SARS-CoV-2 RNA in hospitalized patients have not yet been systematically determined. We conducted a retrospective cohort study of COVID-19 patients in Qingdao, China. Both univariate and multivariate analysis were performed to identify independent factors for time to viral RNA negative conversion. Data on patients with re-detectable viral RNA after showing negative on RT-PCR test (intermittent negative status) were also analyzed. A total of 59 patients confirmed with COVID-19 were included in this study, with a median duration of 1 (interquartile range, IQR: 0–2) day from symptom onset to hospital admission. Median communicable period (from first day of positive nucleic acid test to first day of consecutive negative results) was 14 (IQR: 10–18) days, and 7 (IQR: 6–10) days for 10 patients with intermittent negative results. Age older than 45 years (hazard ratio, HR: 0.378; 95% confidence interval, CI: 0.205–0.698) and chest tightness (HR: 0.290; 95%CI: 0.091–0.919) were factors indecently affecting negative conversion of SARS-CoV-2 RNA. Headache (odds ratio: 7.553; 95%CI: 1.011–28.253) was significantly associated with intermittent negative status, with a predicted probability of 60%. Older age and chest tightness were independently associated with delayed clearance of SARS-CoV-2 RNA in hospitalized patients. These predictors would provide a new perspective on early identification of patients with prolonged viral shedding and facilitate optimal isolation protocols and treatment strategies.


title: Azithromycin and ciprofloxacin have a chloroquine-like effect on respiratory epithelial cells

text: There is interest in the use of chloroquine/hydroxychloroquine (CQ/HCQ) and azithromycin (AZT) in COVID-19 therapy. Employing cystic fibrosis respiratory epithelial cells, here we show that drugs AZT and ciprofloxacin (CPX) act as acidotropic lipophilic weak bases and confer in vitro effects on intracellular organelles similar to the effects of CQ. These seemingly disparate FDA-approved antimicrobials display a common property of modulating pH of endosomes and trans-Golgi network. We believe this may in part help understand the potentially beneficial effects of CQ/HCQ and AZT in COVID-19, and that the present considerations of HCQ and AZT for clinical trials should be extended to CPX.


title: Patterns of HIV prevalence among injecting drug users in the cross-border area of Lang Son Province, Vietnam, and Ning Ming County, Guangxi Province, China

text: BACKGROUND: To assess patterns of injecting drug use and HIV prevalence among injecting drug users (IDUs) in an international border area along a major heroin trans-shipment route. METHODS: Cross-sectional surveys of IDUs in 5 sites in Lang Son Province, Vietnam (n = 348) and 3 sites in Ning Ming County, Guangxi Province, China (n = 308). Respondents were recruited through peer referral ("snowball") methods in both countries, and also from officially recorded lists of IDUs in Vietnam. A risk behavior questionnaire was administered and HIV counseling and testing conducted. RESULTS: Participants in both countries were largely male, in their 20s, and unmarried. A majority of subjects in both countries were members of ethnic minority groups. There were strong geographic gradients for length of drug injecting and for HIV seroprevalence. Both mean years injecting and HIV seroprevalence declined from the Vietnamese site farthest from the border to the Chinese site farthest from the border. 10.6% of participants in China and 24.5% of participants in Vietnam reported crossing the international border in the 6 months prior to interview. Crossing the border by IDUs was associated with (1) distance from the border, (2) being a member of an ethnic minority group, and (3) being HIV seropositive among Chinese participants. CONCLUSION: Reducing the international spread of HIV among IDUs will require programs at the global, regional, national, and "local cross border" levels. At the local cross border level, the programs should be coordinated on both sides of the border and on a sufficient scale that IDUs will be able to readily obtain clean injection equipment on the other side of the border as well as in their country of residence.


title: Directly transmitted viral diseases: modeling the dynamics of transmission

text: A key hurdle in understanding the spread and control of infectious diseases is to capture appropriately the dynamics of pathogen transmission. As people and goods travel increasingly rapidly around the world, so do pathogens; we must be prepared to understand their spread, in terms of the contact network between hosts, viral life history and within-host dynamics. This will require collaborative work that takes into account viral life history, strategy and evolution, and host genetics, demographics and immunodynamics. Mathematical models are a useful tool for integrating the data and analyses from diverse fields that contribute to our understanding of viral transmission dynamics in heterogeneous host populations.


title: It is time to put hurricane preparedness on the radar for individuals living with spinal cord injury

text: Hurricane Dorian’s devastating trajectory over the Northwest Bahamas was the most recent Atlantic storm to call attention to the catastrophic impact of climate change. Although disasters create adversities for all members of the affected population, people with disabilities and special medical needs are disproportionately challenged by such events and are more vulnerable to the conditions they create. This point-counterpoint series highlights the hardships faced by individuals living with spinal cord injury (SCI) when disasters strike. This commentary focuses on the time-urgent need to improve storm readiness among at-risk individuals living with SCI before the start of the upcoming hurricane season. We review the evidence indicating that tropical cyclones are becoming increasingly destructive in the era of climate change and consider how this trend may magnify the difficulties that those with SCI may experience before, during, and in the aftermath of a hurricane. We then review the ways in which health professionals caring for individuals with SCI can help them better prepare for hurricanes while also enhancing their own readiness to provide care during and after an extreme storm.


title: Bird feathers as potential sources of pathogenic microorganisms: a new look at old diseases

text: This article describes methods of treatment for avian zoonoses, modern antibiotic therapy and drug resistance of selected pathogens, which pose a threat to the population’s health. A tabular form has been used to present the current data from the European Union from 2011 to 2017 regarding human morbidity and mortality and the costs incurred by national health systems for the treatment of zoonoses occurring in humans and animals. Moreover, the paper includes descriptions of selected diseases, which indirectly affect birds. Scientists can obtain information regarding the occurrence of particular diseases, their aetiology, epidemiology, incubation period and symptoms caused by dangerous microorganisms and parasites. This information should be of particular interest for people who have frequent contact with birds, such as ornithologists, as well as veterinarians, farm staff, owners of accompanying animals and zoological workers. This paper presents a review used for identification and genetic characterization of bacterial strains isolated from a variety of environmental sources, e.g., bird feathers along with their practical application. We describe the bacterial, viral and fungal serotypes present on avian feathers after the slaughter process. This review also enables us to effectively identify several of the early stages of infectious diseases from heterogeneous avian research material.


title: Eosinophilic granulomatosis with polyangiitis mimicking COVID‐19: a case report

text: Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, is currently spreading worldwide, causing the worst pandemic experienced this century. During the present outbreak, reports have been accumulating that various types of cutaneous manifestations were observed in COVID‐19 patients. We read with interest the recent article by Amatore et al. describing a COVID‐19 case who presented with a febrile rash consisting of annular, polycyclic, and circinate erythema, presumably specific to COVID‐19.


title: The countries getting it right

text: The world can learn lessons from how China, South Korea and Singapore have handled covid-19, the WHO's Bruce Aylward tells Jessica Hamzelou


title: Recombinant Canine Coronaviruses in Dogs, Europe

text: Coronaviruses of potential recombinant origin with porcine transmissible gastroenteritis virus (TGEV), referred to as a new subtype (IIb) of canine coronavirus (CCoV), were recently identified in dogs in Europe. To assess the distribution of the TGEV-like CCoV subtype, during 2001–2008 we tested fecal samples from dogs with gastroenteritis. Of 1,172 samples, 493 (42.06%) were positive for CCoV. CCoV-II was found in 218 samples, and CCoV-I and CCoV-II genotypes were found in 182. Approximately 20% of the samples with CCoV-II had the TGEV-like subtype; detection rates varied according to geographic origin. The highest and lowest rates of prevalence for CCoV-II infection were found in samples from Hungary and Greece (96.87% and 3.45%, respectively). Sequence and phylogenetic analyses showed that the CCoV-IIb strains were related to prototype TGEV-like strains in the 5′ and the 3′ ends of the spike protein gene.


title: Management of diabetic persons with foot ulceration during COVID-19 health care emergency: effectiveness of a new triage pathway

text: Abstract Aim To define the outcomes of persons with diabetes and foot ulcers (DFUs) managed through a specific triage pathway during the COVID-19 crisis. Methods Patients who had an active DFU during the COVID-19 emergency were included. All participants were managed using a specific triage system driven both by ulcer’severity and concomitant co-diseases. Subjects with severely complicated DFUs were urgently referred to hospital regardless of the concomitant comorbidities. Subjects with complicated DFUs received outpatient evaluation (within 48-72 hours) and were admitted to hospital if required (revascularization, surgical intervention, intravenous antibiotic therapy); after the first outpatient visit or hospitalization, patients were followed according to the number of comorbidities (in the case of 3 or more comorbidities patiente were followed up by telemedicine). Patients with uncomplicated DFUs were managed by telemedicine after outpatient evaluation. Healing, major amputation, death and rate of COVID-19 infection were evaluated. The minimum follow-up was 1 month. Results The study group included 151 patients. The mean age was 69.9±14.2 years, 58.9% were male and 91.4% had type 2 diabetes; 58.7% had severely complicated, 21% complicated and 20.3% uncomplicated DFUs. Among those, 78.8% presented with 3 or more comorbidities. One hundred and six patients had regular clinical follow-ups, while 45 were managed through telemedicine. Forty-one (27.1%) patients healed, 3 (1.9%) had major amputations and 3 (1.9%) died. One patient (0.6%) reported COVID-19 positivity due to infection aquired at home. Conclusion The triage pathway adopted during the COVID-19 pandemic showed adequate management of DFUs and no cases of hospital virus exposure.


title: Genetic Variation and Population Differentiation in a Medical Herb Houttuynia cordata in China Revealed by Inter-Simple Sequence Repeats (ISSRs)

text: Houttuynia cordata is an important traditional Chinese herb with unresolved genetics and taxonomy, which lead to potential problems in the conservation and utilization of the resource. Inter-simple sequence repeat (ISSR) markers were used to assess the level and distribution of genetic diversity in 226 individuals from 15 populations of H. cordata in China. ISSR analysis revealed low genetic variations within populations but high genetic differentiations among populations. This genetic structure probably mainly reflects the historical association among populations. Genetic cluster analysis showed that the basal clade is composed of populations from Southwest China, and the other populations have continuous and eastward distributions. The structure of genetic diversity in H. cordata demonstrated that this species might have survived in Southwest China during the glacial age, and subsequently experienced an eastern postglacial expansion. Based on the results of genetic analysis, it was proposed that as many as possible targeted populations for conservation be included.


title: Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease

text: Inclusion body disease (IBD) is an infectious fatal disease of snakes typified by behavioral abnormalities, wasting, and secondary infections. At a histopathological level, the disease is identified by the presence of large eosinophilic cytoplasmic inclusions in multiple tissues. To date, no virus or other pathogen has been definitively characterized or associated with the disease. Using a metagenomic approach to search for candidate etiologic agents in snakes with confirmed IBD, we identified and de novo assembled the complete genomic sequences of two viruses related to arenaviruses, and a third arenavirus-like sequence was discovered by screening an additional set of samples. A continuous boa constrictor cell line was established and used to propagate and isolate one of the viruses in culture. Viral nucleoprotein was localized and concentrated within large cytoplasmic inclusions in infected cells in culture and tissues from diseased snakes. In total, viral RNA was detected in 6/8 confirmed IBD cases and 0/18 controls. These viruses have a typical arenavirus genome organization but are highly divergent, belonging to a lineage separate from that of the Old and New World arenaviruses. Furthermore, these viruses encode envelope glycoproteins that are more similar to those of filoviruses than to those of other arenaviruses. These findings implicate these viruses as candidate etiologic agents of IBD. The presence of arenaviruses outside mammals reveals that these viruses infect an unexpectedly broad range of species and represent a new reservoir of potential human pathogens.


title: Apoptosis and loss of virus-specific CD8+ T-cell memory

text: Abstract CD8+ T-cell memory to viruses is stable in the absence but volatile in the presence of other infections. Apoptotic events that occur early in acute infections delete pre-existing memory T cells, leaving the host with reduced memory (except for cross-reactive responses) to previously encountered viruses. Apoptotic events also silence the acute immune response, leaving the host with a residual population of memory T cells. Persistent infections can induce apoptotic deletions of memory T cells that are specific to the persisting virus and to previously encountered pathogens.


title: Rapid Evolution of PARP Genes Suggests a Broad Role for ADP-Ribosylation in Host-Virus Conflicts

text: Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.


title: Poly(amidoamine) Dendrimer Nanocarriers and Their Aerosol Formulations for siRNA Delivery to the Lung Epithelium

text: [Image: see text] Small interfering RNA (siRNA)-based therapies have great promise in the treatment of a number of prevalent pulmonary disorders including lung cancer, asthma and cystic fibrosis. However, progress in this area has been hindered due to the lack of carriers that can efficiently deliver siRNA to lung epithelial cells, and also due to challenges in developing oral inhalation (OI) formulations for the regional administration of siRNA and their carriers to the lungs. In this work we report the ability of generation four, amine-terminated poly(amidoamine) (PAMAM) dendrimer (G4NH2)–siRNA complexes (dendriplexes) to silence the enhanced green fluorescent protein (eGFP) gene on A549 lung alveolar epithelial cells stably expressing eGFP. We also report the formulation of the dendriplexes and their aerosol characteristics in propellant-based portable OI devices. The size and gene silencing ability of the dendriplexes was seen not to be a strong function of the N/P ratio. Silencing efficiencies of up to 40% are reported. Stable dispersions of the dendriplexes encapsulated in mannitol and also in a biodegradable and water-soluble co-oligomer were prepared in hydrofluoroalkane (HFA)-based pressurized metered-dose inhalers (pMDIs). Their aerosol characteristics were very favorable, and conducive to deep lung deposition, with respirable fractions of up to 77%. Importantly, siRNA formulated as dendriplexes in pMDIs was shown to keep its integrity after the particle preparation processes, and also after long-term exposures to HFA. The relevance of this study stems from the fact that this is the first work to report the formulation of inhalable siRNA with aerosol properties suitable to deep lung deposition using pMDIs devices that are the least expensive and most widely used portable inhalers. This study is relevant because, also for the first time, it shows that siRNA–G4NH2 dendriplexes can efficiently target lung alveolar epithelial A549 cells and silence genes even after siRNA has been exposed to the propellant environment.


Management of the airway and lung isolation for thoracic surgery during the COVID‐19 pandemic: a reply


title: Chapter 21 The Viruses of the Gut Microbiota

text: Abstract The gut virome is the viral component of the gut microbiome. Knowledge regarding its composition, interindividual and temporal variability is increasing, and the significance of its impact on human health, both in homeostasis and disease is being recognized. Here we review the recent advances in this field, and the questions that arise in the context of the rapidly increasing information regarding its composition and function. With the extending collection of human data, the power of next generation sequencing, and functional studies, the factors that influence the composition of the gut virome and its impact on human health will be further refined in the coming years.


title: FIP's response to the COVID-19 pandemic: Global pharmacy rises to the challenge

text: The International Pharmaceutical Federation (FIP), as the global leadership body for pharmacists, pharmaceutical scientists and pharmaceutical educators, coordinated and produced as of January 2020 an international response to the COVID-19 pandemic. FIP's response included professional guidance, a programme of digital events and other resources, as well as advocacy and policy tools to support national pharmacists' associations and academic institutions, as well as individual practitioners, in their response at country level. This article describes the strategy adopted by FIP in collaboration with an international group of experts to support the valuable service that pharmacists and their teams provide to communities throughout the pandemic, and their important contribution to easing the huge strain being placed on health systems around the world.


title: Parechovirus A Pathogenesis and the Enigma of Genotype A-3

text: Parechovirus A is a species in the Parechovirus genus within the Picornaviridae family that can cause severe disease in children. Relatively little is known on Parechovirus A epidemiology and pathogenesis. This review aims to explore the Parechovirus A literature and highlight the differences between Parechovirus A genotypes from a pathogenesis standpoint. In particular, the curious case of Parechovirus-A3 and the genotype-specific disease association will be discussed. Finally, a brief outlook on Parechovirus A research is provided.


title: Obesity and Outcomes in COVID-19: When an Epidemic and Pandemic Collide

text: Abstract Obesity has reached epidemic proportions in the United States and in much of the Westernized World, contributing to considerable morbidity. Several of these obesity-related morbidities are associated with greater risk of death with Coronavirus 2019 (COVID-19). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates human cells through direct binding with angiotensin-converting enzyme (ACE) 2 receptors on the cell surface. ACE2 expression in adipose tissue is higher than that in lung tissue, which means that adipose tissue may be vulnerable to COVID-19 infection. Obese patients also have worse outcomes with COVID-19, including respiratory failure, need for mechanical ventilation, and higher mortality. Clinicians need to be more aggressive when treating obese, especially severely obese, patients with COVID-19.


title: Fusion resistance and decreased infectability as major host cell determinants of coronavirus persistence

text: Abstract Mouse hepatitis virus persists in cultures of a subline (designated LM-K) of mouse LM cells but produces a lytic infection in L-2 cells. Persistence in the LM-K cells was not accompanied by production of is mutants or of soluble anti-MHV factors. Infectious center assay demonstrated an approximately 500-fold lower level of infectibility by MHV of the LM-K cells as compared to L-2 cells. On an infected cell basis, production levels of infectious progeny and viral RNA were comparable between the two cell lines. The extent of virus-induced cell-cell fusion, however, was markedly reduced in the LM-K cells. Cell-mixing experiments showed that both infected L-2 and LM-K cells have the capacity of fusing with neighboring uninfected L-2 cells but not with uninfected LM-K cells. This suggests that the decreased level of fusion observed in the LM-K infection is due not to absence of viral fusion protein at the cell surface, but rather to an inherent resistance of the LM-K cell membrane to MHV-induced fusion. It is believed that such fusion resistance in LM-K cells moderates virus dissemination throughout the culture, thereby contributing to a state of virus persistence.


title: A Bibliometric Analysis of Publications on Pluripotent Stem Cell Research

text: OBJECTIVE: Human pluripotent stem cells are self-renewing cells with the ability to differentiate into a variety of cells and are viewed to have great potential in the field of regenerative medicine. Research in pluripotent stem cells holds great promise for patient specific therapy in various diseases. In this study, pluripotent stem cell articles published from 1991 to 2012 were screened and retrieved from Science Citation Index Expanded (SCI-EXPANDED). MATERIALS AND METHODS: In this retrospective study, the publication trend, citation trends for top articles, distributions of journals and Web of Science categories were analyzed. Five bibliometric indicators including total articles, independent articles, collaborative articles, first author articles, and corresponding author articles were applied to compare publications between countries and institutions. RESULTS: The impact of top articles changed from year to year. Top cited articles in previous publication years were not the same as recent years. "Induced pluripotent stem cell (s)" and "embryonic stem cell (s)" were the most used author keywords in pluripotent stem cell research. In addition, the winner of the Nobel Prize in physiology or medicine in 2012, Prof. Shinya Yamanaka, published four of the top ten most frequently cited articles. CONCLUSION: The comprehensive analysis of highly cited articles in the stem cell field could identify milestones and important contributors, giving a historic perspective on scientific progress.


title: SARS – Pandemie und Emerging Disease

text: The SARS-epidemic of 2002/2003 with worldwide 8.096 cases and 774 fatalities was the first pandemia of the 21(st) century. SARS, the severe acute respiratory syndrome, arose in southern China and spread from Southeast-Asia finally over all five continents. It caused heavy pneumonia with pulmonal failure and enteric involvement in man. The causative agent was a novel coronavirus (SARS-CoV), which was transmitted from bats to small carnivores and from them to man. The mutations of the viral receptor gene thus allowed the infection of man and the transmission from man to man. The SARS-pandemia can therefore be regarded as a model of an emerging disease.


title: Role of Tissue Engineering in COVID-19 and Future Viral Outbreaks

text: In light of the current novel coronavirus (COVID-19) pandemic, as well as other viral outbreaks in the 21st century, there is a dire need for new diagnostic and therapeutic strategies to combat infectious diseases worldwide. As a convergence science, tissue engineering has traditionally focused on the application of engineering principles to biological systems, collaboration across disciplines, and rapid translation of technologies from the benchtop to the bedside. Given these strengths, tissue engineers are particularly well suited to apply their skill set to the current crisis and viral outbreaks in general. This work introduces the basics of virology and epidemiology for tissue engineers, and highlights important developments in the field of tissue engineering relevant to the current pandemic, including in vitro model systems, vaccine technology, and small-molecule drug delivery. COVID-19 serves as a call to arms for scientists across all disciplines, and tissue engineers are well trained to be leaders and contributors in this time of need. IMPACT STATEMENT: Given the steep mortality caused by the recent novel coronavirus (COVID-19) pandemic, there is clear need for advances in diagnostics and therapeutics for viral outbreaks. Tissue engineering has the potential for critical impact on clinical outcomes in viral outbreaks. Tissue engineers, if mobilized, could play key roles as leaders in the outbreak, given their ability to apply engineering principles to biological processes, experience in collaborative environments, and penchant for technological translation from benchtop to bedside. In this work, three areas pioneered by tissue engineers that could be applied to the current COVID-19 crisis and future viral outbreaks are highlighted.


title: A chemokine gene expression signature derived from meta-analysis predicts the pathogenicity of viral respiratory infections

text: BACKGROUND: During respiratory viral infections host injury occurs due in part to inappropriate host responses. In this study we sought to uncover the host transcriptional responses underlying differences between high- and low-pathogenic infections. RESULTS: From a compendium of 12 studies that included responses to influenza A subtype H5N1, reconstructed 1918 influenza A virus, and SARS coronavirus, we used meta-analysis to derive multiple gene expression signatures. We compared these signatures by their capacity to segregate biological conditions by pathogenicity and predict pathogenicity in a test data set. The highest-performing signature was expressed as a continuum in low-, medium-, and high-pathogenicity samples, suggesting a direct, analog relationship between expression and pathogenicity. This signature comprised 57 genes including a subnetwork of chemokines, implicating dysregulated cell recruitment in injury. CONCLUSIONS: Highly pathogenic viruses elicit expression of many of the same key genes as lower pathogenic viruses but to a higher degree. This increased degree of expression may result in the uncontrolled co-localization of inflammatory cell types and lead to irreversible host damage.


title: COVID-19 the showdown for mass casualty preparedness and management: the Cassandra Syndrome

text: Since December 2019, the world is potentially facing one of the most difficult infectious situations of the last decades. COVID-19 epidemic warrants consideration as a mass casualty incident (MCI) of the highest nature. An optimal MCI/disaster management should consider all four phases of the so-called disaster cycle: mitigation, planning, response, and recovery. COVID-19 outbreak has demonstrated the worldwide unpreparedness to face a global MCI. This present paper thus represents a call for action to solicitate governments and the Global Community to actively start effective plans to promote and improve MCI management preparedness in general, and with an obvious current focus on COVID-19.


title: Type I interferon receptor-independent and -dependent host transcriptional responses to mouse hepatitis coronavirus infection in vivo

text: BACKGROUND: The role of type I IFNs in protecting against coronavirus (CoV) infections is not fully understood. While CoVs are poor inducers of type I IFNs in tissue culture, several studies have demonstrated the importance of the type I IFN response in controlling MHV infection in animals. The protective effectors against MHV infection are, however, still unknown. RESULTS: In order to get more insight into the antiviral gene expression induced in the brains of MHV-infected mice, we performed whole-genome expression profiling. Three different mouse strains, differing in their susceptibility to infection with MHV, were used. In BALB/c mice, which display high viral loads but are able to control the infection, 57 and 121 genes were significantly differentially expressed (≥ 1.5 fold change) upon infection at 2 and 5 days post infection, respectively. Functional association network analyses demonstrated a strong type I IFN response, with Irf1 and Irf7 as the central players. At 5 days post infection, a type II IFN response also becomes apparent. Both the type I and II IFN response, which were more pronounced in mice with a higher viral load, were not observed in 129SvEv mice, which are much less susceptible to infection with MHV. 129SvEv mice lacking the type I interferon receptor (IFNAR-/-), however, were not able to control the infection. Gene expression profiling of these mice identified type I IFN-independent responses to infection, with IFN-γ as the central player. As the BALB/c and the IFNAR-/- 129SvEv mice demonstrated very similar viral loads in their brains, we also compared their gene expression profiles upon infection with MHV in order to identify type I IFN-dependent transcriptional responses. Many known IFN-inducible genes were detected, several of which have previously been shown to play an important protective role against virus infections. We speculate that the additional type I IFN-dependent genes that we discovered may also be important for protection against MHV infection. CONCLUSION: Transcriptional profiling of mice infected with MHV demonstrated the induction of a robust IFN response, which correlated with the viral load. Profiling of IFNAR-/- mice allowed us to identify type I IFN-independent and -dependent responses. Overall, this study broadens our present knowledge of the type I and II IFN-mediated effector responses during CoV infection in vivo.


title: Rhesus Theta Defensin 1 Promotes Long Term Survival in Systemic Candidiasis by Host Directed Mechanisms

text: Invasive candidiasis is an increasingly frequent cause of serious and often fatal infections in hospitalized and immunosuppressed patients. Mortality rates associated with these infections have risen sharply due to the emergence of multidrug resistant (MDR) strains of C. albicans and other Candida spp., highlighting the urgent need of new antifungal therapies. Rhesus theta (θ) defensin-1 (RTD-1), a natural macrocyclic antimicrobial peptide, was recently shown to be rapidly fungicidal against clinical isolates of MDR C. albicans in vitro. Here we found that RTD-1 was rapidly fungicidal against blastospores of fluconazole/caspofungin resistant C. albicans strains, and was active against established C. albicans biofilms in vitro. In vivo, systemic administration of RTD-1, initiated at the time of infection or 24 h post-infection, promoted long term survival in candidemic mice whether infected with drug-sensitive or MDR strains of C. albicans. RTD-1 induced an early (4 h post treatment) increase in neutrophils in naive and infected mice. In vivo efficacy was associated with fungal clearance, restoration of dysregulated inflammatory cytokines including TNF-α, IL-1β, IL-6, IL-10, and IL-17, and homeostatic reduction in numbers of circulating neutrophils and monocytes. Because these effects occurred using peptide doses that produced maximal plasma concentrations (Cmax) of less than 1% of RTD-1 levels required for in vitro antifungal activity in 50% mouse serum, while inducing a transient neutrophilia, we suggest that RTD-1 mediates its antifungal effects in vivo by host directed mechanisms rather than direct fungicidal activity. Results of this study suggest that θ-defensins represent a new class of host-directed compounds for treatment of disseminated candidiasis.


title: Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice

text: Abstract Houttuynia cordata polysaccharide (HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg(kg−1(d−1. H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.


title: Structure-based identification of functional residues in the nucleoside-2′-O-methylase domain of Bluetongue virus VP4 capping enzyme

text: Bluetongue virus (BTV) encodes a single capping protein, VP4, which catalyzes all reactions required to generate cap1 structures on nascent viral transcripts. Further, structural analysis by X-ray crystallography indicated each catalytic reaction is arranged as a discrete domain, including a nucleoside-2′-O-methyltransferase (2′-O MTase). In this study, we have exploited the structural information to identify the residues that are important for the catalytic activity of 2′-O MTase of VP4 and their influence on BTV replication. The effect of these mutations on GMP binding, guanylyltransferase (GTase) and methylase activities were analysed by a series of in vitro biochemical assays using recombinant mutant proteins; subsequently their effects on virus replication were assessed by introducing the same mutations in replicating viral genome using a reverse genetics system. Our data showed that single substitution mutations in the catalytic tetrad K-D-K-E were sufficient to abolish 2′-O MTase activity in vitro and to completely abrogate BTV replication in cells; although these mutants retained the upstream GMP binding, GTase and guanine-N7-methyltransferase activities. Mutations of the surrounding substrate-binding pocket (predicted to recruit cap0) had variable effects on in vitro VP4 capping activity. Only triple but not single substitution mutations of these residues in genome resulted in reduced virus replication kinetics. This is the first report investigating the importance of 2′-O MTase function for any member of the Reoviridae and highlights the significance of K-D-K-E tetrad and surrounding residues for the efficiency of 2′-O MTase activity and in turn, for virus fitness.


Response to “Risks of Hydroxychloroquine use for COVID-19 prophylaxis”


A career in a Kingdom: Journeys in infection, Mass Gathering Medicine and public health diplomacy


title: Chapter 8 Infectious Disease Surveillance and Early Warning System During Beijing Olympic Games

text: Abstract To detect the outbreak or epidemic earlier and ensure the public health security during Olympic Games in Beijing, Beijing Olympic Games Infectious Disease Surveillance System (BOG-IDSS) was established based on a series of routine surveillance systems. Early warning algorithms were applied to early detect aberrations. Results showed that BOG-IDSS, especially the newly established Syndromic Surveillance System for Beijing Olympic Games could effectively protect the security of public health during mass gatherings.


title: Neonatal Immunity, Respiratory Virus Infections, and the Development of Asthma

text: Infants are exposed to a wide range of potential pathogens in the first months of life. Although maternal antibodies acquired transplacentally protect full-term neonates from many systemic pathogens, infections at mucosal surfaces still occur with great frequency, causing significant morbidity and mortality. At least part of this elevated risk is attributable to the neonatal immune system that tends to favor T regulatory and Th2 type responses when microbes are first encountered. Early-life infection with respiratory viruses is of particular interest because such exposures can disrupt normal lung development and increase the risk of chronic respiratory conditions, such as asthma. The immunologic mechanisms that underlie neonatal host–virus interactions that contribute to the subsequent development of asthma have not yet been fully defined. The goals of this review are (1) to outline the differences between the neonatal and adult immune systems and (2) to present murine and human data that support the hypothesis that early-life interactions between the immune system and respiratory viruses can create a lung environment conducive to the development of asthma.


title: Fluorescent Quantum Dots-Zika Virus Hybrid Nanoconjugates for Biolabeling, Bioimaging, and Tracking Host-Cell Interactions

text: The earliest possible diagnosis and understanding of the infection mechanisms play a crucial role in the outcome of fighting viral diseases. Thus, we designed and developed for the first time, novel bioconjugates made of Ag-In-S@ZnS (ZAIS) fluorescent quantum dots coupled with ZIKA virus via covalent amide bond with carboxymethylcellulose (CMC) biopolymer for labeling and bioimaging the virus-host cell interactions mechanisms through confocal laser scanning microscopy. This work offers relevant insights regarding the profile of the ZIKA virus-nanoparticle conjugates interactions with VERO cells, which can be applied as a nanoplatform to elucidate the infection mechanisms caused by this viral disease.


title: CNS Penetration Ability: A Critical Factor for Drugs in the Treatment of SARS-CoV-2 Brain Infection

text: Now, it has been evidenced that Covid19 (SARS-CoV-2) infects the brain tissues. Along with this, a challenge has been raised for research professionals to find effective drugs for its treatment since the recent spread of this virus from Wuhan, China. Targeting the treatment of brain infection, it has also been a challenge that the clinical drug should have good CNS penetration ability to cross the blood–brain barrier.


title: Life threatening pneumonia in a lupus patient: a case report

text: We report a case of systemic lupus erythematosus (SLE) in a 44-year old Caucasian woman complicated with pneumonia and severe respiratory failure requiring ICU treatment and mechanical ventilation. Symptoms developed in a generally well controlled SLE course after sudden stop in immunosupresant therapy (methotrexate, cyclosporin and methylprednisolone). A fulminant course of the disease, an interstitial pattern in a high resolution computed tomography (HRCT) and negative repeated sputum, blood and bronchoaspirate cultures enabled diagnosis of fulminant lupus pneumonitis. The response to pulses of cyclophosphamide and methylprednisolone was good but complicated with a significant leukopenia. HRCT confirmed significant remission of pulmonary changes. Fulminant lupus pneumonitis is a rare but potentially life threatening complication of SLE. Differential diagnosis requires exclusion of pneumonia induced by pathogens such as Pneumocystis jirovevecii (carinii) and Mycobacterium sp. Intensive immunosuppressive therapy and close cooperation between ICU, pulmonology and rheumatology departments is necessary in such a case to minimalize the risk of fatal outcome.


title: A newly reported human polyomavirus, KI virus, is present in the respiratory tract of Australian children

text: Abstract Background Recently, Allander and co-workers reported the discovery of a new human polyomavirus, KI virus, in respiratory secretions from patients with acute respiratory tract infection (ARTI). Objective We examined 951 respiratory samples collected in Queensland, Australia, between November 2002 and August 2003 from patients with respiratory infection, for the presence of the KI virus. Results Twenty-four (2.5%) samples were positive for KI virus with 20 (83%) of these from children younger than 5 years. In six (25%) patients KI was co-detected with another virus. Full genome sequencing of three isolates shows a high degree of conservation between the Queensland isolates and the original isolates reported from Swedish patients. Conclusions The newly described KI polyomavirus may commonly be found in the respiratory tract of patients with ARTI, particularly children, and results indicate that the virus has global presence.


title: Near-patient assays for diagnosis of influenza virus infection in adult patients

text: Rapid and reliable diagnosis of influenza is essential for identification of contagious patients and effective patient management. Near-patient assays allow establishment of the diagnosis within minutes in young children, and this study aimed to evaluate near-patient assays in relation to the patient’s age. A total of 194 patients with laboratory-confirmed influenza A/H3N2 virus infection, diagnosed within a prospective cohort study, were included. Cryopreserved nasopharyngeal swabs collected from these patients were tested by four near-patient assays (Binax Now Influenza A&B, Quick S-Influ A/B, Influ-A&B Respi-Strip, and Actim Influenza A&B). The main outcome measure was sensitivity of the near-patient assays in relation to the age of patients. The Binax Now, Quick S-Influ, Influ-A&B Respi-Strip and Actim assays had overall sensitivities of 19%, 18%, 26%, and 40%, respectively. The estimated sensitivity for influenza A/H3N2 virus detection in nasopharyngeal swabs was 17–56% in children 1 year of age and decreased to 8–22% in patients 80 years of age (logistic regression). The sensitivity of the Influ-A&B Respi-Strip and Actim assays decreased significantly with increasing age (p 0.014 and p 0.033, respectively (logistic regression)), a trend for decrease was observed for the Binax Now assay (p 0.074 (logistic regression)), and the low sensitivity of the Quick S-Influ assay was similar in children and adults. Less than one-fourth of diagnosed influenza A/H3N2 virus infections can be identified in elderly patients using a near-patient assay. Consequently, near-patient assays are of limited value for confirming the diagnosis when influenza is clinically suspected in adults. Antiviral therapy and additional diagnostic procedures cannot be withheld on the basis of a negative near-patient assay result, particularly in adult patients.


Lessons learned from the coronavirus health crisis in Madrid, Spain: How COVID-19 has changed our lives in the last two weeks


title: Impact of temperature on the dynamics of the COVID-19 outbreak in China

text: Abstract A COVID-19 outbreak emerged in Wuhan, China at the end of 2019 and developed into a global pandemic during March 2020. The effects of temperature on the dynamics of the COVID-19 epidemic in China are unknown. Data on COVID-19 daily confirmed cases and daily mean temperatures were collected from 31 provincial-level regions in mainland China between Jan. 20 and Feb. 29, 2020. Locally weighted regression and smoothing scatterplot (LOESS), distributed lag nonlinear models (DLNMs), and random-effects meta-analysis were used to examine the relationship between daily confirmed cases rate of COVID-19 and temperature conditions. The daily number of new cases peaked on Feb. 12, and then decreased. The daily confirmed cases rate of COVID-19 had a biphasic relationship with temperature (with a peak at 10 °C), and the daily incidence of COVID-19 decreased at values below and above these values. The overall epidemic intensity of COVID-19 reduced slightly following days with higher temperatures with a relative risk (RR) was 0.96 (95% CI: 0.93, 0.99). A random-effect meta-analysis including 28 provinces in mainland China, we confirmed the statistically significant association between temperature and RR during the study period (Coefficient = −0.0100, 95% CI: −0.0125, −0.0074). The DLNMs in Hubei Province (outside of Wuhan) and Wuhan showed similar patterns of temperature. Additionally, a modified susceptible-exposed-infectious-recovered (M-SEIR) model, with adjustment for climatic factors, was used to provide a complete characterization of the impact of climate on the dynamics of the COVID-19 epidemic.


title: How to improve adherence with quarantine: Rapid review of the evidence

text: Abstract Objectives The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to ‘self-isolate’ if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design Rapid evidence review. Methods We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.


title: Neonatal Late Onset Infection with Severe Acute Respiratory Syndrome Coronavirus 2

text: Objective To date, no information on late-onset infection in newborns to mother with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contracted in pregnancy are available. This study aimed to evaluate postdischarge SARS-CoV-2 status of newborns to mothers with COVID-19 in pregnancy that, at birth, were negative to SARS-CoV-2. Study Design This is an observational study of neonates born to mothers with coronavirus disease 2019 (COVID-19). Results Seven pregnant women with documented SARS-CoV-2 infection have been evaluated in our institution. One woman had a spontaneous abortion at 8 weeks of gestational age, four women recovered and are still in follow-up, and two women delivered. Two newborns were enrolled in the study. At birth and 3 days of life, newborns were negative to SARS-CoV-2. At 2-week follow-up, one newborn tested positive although asymptomatic. Conclusion Our findings highlight the importance of follow-up of newborns to mothers with COVID-19 in pregnancy, since they remain at risk of contracting the infection in the early period of life and long-term consequences are still unknown. Key Points: Newborns to mothers with coronavirus disease 2019 (COVID-19) in pregnancy can acquire the infection later after birth. Newborns to mothers with COVID-19 in pregnancy need a long-term follow-up, even if they tested negative at birth. Specific guidelines for the long-term follow-up of newborns to mothers with COVID-19 in pregnancy are needed.


title: Porcine epidemic diarrhea virus induces caspase-independent apoptosis through activation of mitochondrial apoptosis-inducing factor

text: Abstract The present study sought to investigate whether porcine epidemic diarrhea virus (PEDV) induces apoptosis and to elucidate the mechanisms associated with apoptotic cell death after PEDV infection. PEDV-infected cells showed evidence of apoptosis in vitro and in vivo. However, experimental data indicated that the caspase cascade is not involved in PEDV-induced apoptotic cell death. Interestingly, mitochondrial apoptosis-inducing factor (AIF) was found to translocate to the nucleus during PEDV infection, and AIF relocalization was completely abrogated by the presence of cyclosporin A (CsA), an inhibitor of cyclophilin D (CypD) that is an essential component of the mitochondrial permeabilization transition pore (mPTP) complex. CsA treatment resulted in significant inhibition of PEDV-triggered apoptosis and suppressed PEDV replication. Furthermore, direct inhibition of AIF strongly impaired PEDV infection and virus-induced apoptosis. Altogether, our results indicate that a caspase-independent mitochondrial AIF-mediated pathway plays a central role in PEDV-induced apoptosis to facilitate viral replication and pathogenesis.


Neuroinfecciones en tiempos de COVID-19


title: H7 virus-like particles assembled by hemagglutinin containing H3N2 transmembrane domain and M1 induce broad homologous and heterologous protection in mice

text: Influenza A H7N9 virus has caused five outbreak waves of human infections in China since 2013 and posed a dual challenge to public health and poultry industry. There is an urgent need to develop an effective vaccine to reduce its pandemic potential. In the present study, we evaluated the biochemical characteristics and immunogenicity of two H7 virus-like particles (VLPs) composed of the matrix 1 (M1) and hemagglutinin of wild-type (HA-WT) or hemagglutinin of whose transmembrane domain replaced by that from H3N2 subtype (HA-TM). H7 VLPs-WT and H7 VLPs-TM could assemble and release into the supernatant of Sf9 cells and they had similar morphological characteristics. However, compared to H7 VLPs-WT, H7 VLPs-TM had more trimeric HA proteins and could better resist thermal changes. In mice H7 VLPs-TM induced higher titers of HI, IgG, IgG2a and IFN-γ, and provided better protection against homologous and heterologous H7N9 viruses (no matter belonging to Yangtze River Delta or Pearl River Delta) challenge with less weight loss and higher survival rate. In summary, H7 VLPs-TM represents a potential strategy for the development of H7N9 vaccines.


title: Whole-genome patenting

text: Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. When these patents are analysed and compared to those for other biological entities, it becomes clear that genome patents seek to exploit the genome as an information base and are part of a broader shift towards intangible intellectual property in genomics.


title: Intrusion of software robots into journalism: The public's and journalists' perceptions of news written by algorithms and human journalists

text: Abstract This study adopted a two (author: algorithm or journalist) by two (notification of author: real or inverse) between subject design to investigate how the public and journalists perceive the quality of algorithms-written articles compared with human journalist's work. Findings showed that both the public and journalists' evaluations were varied by the manipulation of author notification. That is, the public gave higher scores to the algorithm's work when it was notified as the real author, but they gave lower scores to the algorithm's work when the author was notified as a journalist. It confirmed the public's negative attitude toward journalists' credibility and craving for new information and communication technology (ICT) products/services in Korea. Based on journalists' resistance to change and innovation and the theory of prejudice, it was expected that journalists would be favorable to another journalist's work and unfavorable to an algorithm's work. However, contrary to the hypothetical expectation, journalists also gave higher scores to an algorithm's work and lower scores to a journalist's work. Implications relating to the intrusion of algorithm-written articles into journalism were discussed.


Antibody-Mediated Virus Clearance from Neurons of Rats Infected with Hemagglutinating Encephalomyelitis Virus


title: SARS coronavirus spike polypeptide DNA vaccine priming with recombinant spike polypeptide from Escherichia coli as booster induces high titer of neutralizing antibody against SARS coronavirus

text: Different forms of SARS coronavirus (SARS-CoV) spike protein-based vaccines for generation of neutralizing antibody response against SARS-CoV were compared using a mouse model. High IgG levels were detected in mice immunized with intraperitoneal (i.p.) recombinant spike polypeptide generated by Escherichia coli (S-peptide), mice primed with intramuscular (i.m.) tPA-optimize800 DNA vaccine (tPA-S-DNA) and boosted with i.p. S-peptide, mice primed with i.m. CTLA4HingeSARS800 DNA vaccine (CTLA4-S-DNA) and boosted with i.p. S-peptide, mice primed with oral live-attenuated Salmonella typhimurium (Salmonella-S-DNA-control) and boosted with i.p. S-peptide, mice primed with oral live-attenuated S. typhimurium that contained tPA-optimize800 DNA vaccine (Salmonella-tPA-S-DNA) and boosted with i.p. S-peptide, and mice primed with oral live-attenuated S. typhimurium that contained CTLA4HingeSARS800 DNA vaccine (Salmonella-tPA-S-DNA) and boosted with i.p. S-peptide. No statistical significant difference was observed among the Th1/Th2 index among these six groups of mice with high IgG levels. Sera of all six mice immunized with i.p. S-peptide, i.m. DNA vaccine control and oral Salmonella-S-DNA-control showed no neutralizing antibody against SARS-CoV. Sera of the mice immunized with i.m. tPA-S-DNA, i.m. CTLA4-S-DNA, oral Salmonella-S-DNA-control boosted with i.p. S-peptide, oral Salmonella-tPA-S-DNA, oral Salmonella-tPA-S-DNA boosted with i.p S-peptide, oral Salmonella-CTLA4-S-DNA and oral Salmonella-CTLA4-S-DNA boosted with i.p. S-peptide showed neutralizing antibody titers of <1:20–1:160. Sera of all the mice immunized with i.m. tPA-S-DNA boosted with i.p. S-peptide and i.m. CTLA4-S-DNA boosted with i.p. S-peptide showed neutralizing antibody titers of ≥1:1280. The present observation may have major practical value, such as immunization of civet cats, since production of recombinant proteins from E. coli is far less expensive than production of recombinant proteins using eukaryotic systems.


title: Importance de la PCR dans la gestion d’une épidémie à Mycoplasma pneumoniae au centre hospitalier de Béthune (Pas-de-Calais)

text: Résumé Objet La biologie moléculaire (PCR) constitue une aide rapide et spécifique pour le diagnostic différentiel des infections respiratoires à mycoplasme, première cause de pneumonies communautaires chez l’enfant de plus de cinq ans. Méthode Positivité de la PCR (Chlamylège®, Argène) (aspiration nasopharyngée, prélèvements respiratoires, écouvillonnage nasophayngé) et/ou du sérodiagnostic (Elisa). Résultats Trente-neuf cas diagnostiqués : 31 entre septembre et décembre 2008 (30 enfants et un adulte) et huit depuis juin 2009 (trois adultes et cinq enfants). Les enfants (âge moyen : 3,6 ans) ont été hospitalisés dans 88,6 % des cas pendant 2,9 jours pour atteinte respiratoire haute ou basse, avec surtout échec de traitement aux β-lactamines (65,7 % des cas). Les quatre adultes (âge moyen : 29,5 ans) ont présenté une pneumopathie, avec hospitalisation pour trois d’entre eux dont un en réanimation. Vingt-huit PCR sur 32 se sont avérées positives (87 %) : sans sérologie associée (13), sérologies négatives (huit), IgG et IgM positives (cinq) et IgG seules (deux). Pour sept patients, seule la sérologie a été réalisée : IgM±IgG. Pour deux enfants, IgM positive isolément, avec une PCR probablement faussement négative (prélèvement paucicellulaire). Conclusion La sensibilité de la sérologie dans le diagnostic des infections à mycoplasmes reste limitée : les IgM qui apparaissent généralement une semaine après le début des signes cliniques sont le plus souvent absentes chez l’adulte et élévation tardive des IgG. Le diagnostic précoce des pneumopathies de l’enfant par PCR a permis de caractériser rapidement ce phénomène épidémique et d’adapter les thérapeutiques. Abstract Subject Molecular amplification (PCR) provides adequate rapid and specific diagnosis of Mycoplasma pneumoniae infection (first agent responsible for community-wide bacterial pneumonia in children above 5 years of age). Method Positive (Chlamylège®, Argène) PCR in nasopharyngeal aspirate, respiratory samples and nasopharyngeal swab and/or positive serological test (ELISA). Results Diagnosis of M. pneumoniae infection in 39 cases: 31 between September and December 2008 (30 children and one adult) and eight since June 2009 (three adults and five children). Children (mean age: 3.6years) were hospitalized in 88.6% of cases, mean hospitalization duration was 2.9 days for respiratory tract infections, mainly due to lack of response to β-lactamines therapy (65.7%). Four adults (mean age: 29.5 years) presented a pneumonia, with hospitalization for three of them with one in intensive care unit. Twenty-eight PCR have proved positive (87%): without associated serology (13), eight negative serologies, IgG and IgM positive (five), and IgG alone (two). Seven patients had only serological test for diagnosis: IgM±IgG. For two children, IgM positive only in isolation, with a PCR probably false negative. Conclusion The sensitivity of the serology in the diagnosis of mycoplasma infection is limited: IgM, which appear traditionally 1 week after clinical signs are mostly inexistent for adults and IgG rise at a later stage. Early diagnosis of child pneumoniae by PCR helped rapidly characterize this epidemic phenomenon and adapt the treatment.


title: Flying the Unfriendly Skies: A Case Report

text: Abstract We report the case of an older adult foreign national with severe respiratory failure who was brought via a commercial airline to the United States. Hospitalized and orally intubated in his home country, his son, a US citizen, decided to translocate his father to the United States. He purchased tickets for adjoining seats on a prominent international commercial airline and brought his orally intubated, stretcher-bound father onto the plane without any accompanying medical professionals, security screening, or preapproved transport. Despite this, they traveled to New York and phoned 911 upon landing, allowing him to bypass the standard customs procedures.


COVID-19, healthcare workers and future mental health issues


title: Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long‐wavelength ultraviolet light

text: BACKGROUND: Viral contamination of platelet (PLT) concentrates can result in transfusion‐transmitted diseases. A photochemical treatment (PCT) process with amotosalen‐HCl and long‐wavelength ultraviolet light (UVA), which cross‐links nucleic acids, was developed to inactivate viruses and other pathogens in PLT concentrates. STUDY DESIGN AND METHODS: High titers of pathogenic or blood‐borne viruses, representing 10 different families, were added to single‐donor PLT concentrates containing 3.0 × 10(11) to 6.0 × 10(11) PLTs in approximately 300 mL of 35 percent plasma and 65 percent PLT additive solution (InterSol). After PCT with 150 µmol per L amotosalen and 3 J per cm(2) UVA, residual viral infectivity was assayed by sensitive cell culture or animal systems. RESULTS: Enveloped viruses were uniformly sensitive to inactivation by PCT whereas nonenveloped viruses demonstrated variable inactivation. Log reduction of enveloped viruses for cell‐free HIV‐1 was >6.2; for cell‐associated HIV‐1, >6.1; for clinical isolate HIV‐1, >3.4; for clinical isolate HIV‐2, >2.5; for HBV, >5.5; for HCV, >4.5; for DHBV, >6.2; for BVDV, >6.0; for HTLV‐I, 4.2; for HTLV‐II, 4.6; for CMV, >5.9; for WNV, >5.5; for SARS‐HCoV, >5.8; and for vaccinia virus, >4.7. Log reduction of nonenveloped viruses for human adenovirus 5 was >5.2; for parvovirus B19, 3.5‐>5.0; for bluetongue virus, 5.6‐5.9; for feline conjunctivitis virus, 1.7‐2.4; and for simian adenovirus 15, 0.7‐2.3. CONCLUSION: PCT inactivates a broad spectrum of pathogenic, blood‐borne viruses. Inactivation of viruses in PLT concentrates with amotosalen and UVA offers the potential to prospectively prevent the majority of PLT transfusion‐associated viral diseases.


title: Genetic host specificity of hepatitis E virus

text: Hepatitis E virus (HEV) causes epidemic and sporadic cases of hepatitis worldwide. HEV genotypes 3 (HEV3) and 4 (HEV4) infect humans and animals, with swine being the primary reservoir. The relevance of HEV genetic diversity to host adaptation is poorly understood. We employed a Bayesian network (BN) analysis of HEV3 and HEV4 to detect epistatic connectivity among protein sites and its association with the host specificity in each genotype. The data imply coevolution among ~70% of polymorphic sites from all HEV proteins and association of numerous coevolving sites with adaptation to swine or humans. BN models for individual proteins and domains of the nonstructural polyprotein detected the host origin of HEV strains with accuracy of 74–93% and 63–87%, respectively. These findings, taken together with lack of phylogenetic association to host, suggest that the HEV host specificity is a heritable and convergent phenotypic trait achievable through variety of genetic pathways (abundance), and explain a broad host range for HEV3 and HEV4.