title: Human Monoclonal Antibodies against Highly Conserved HR1 and HR2 Domains of the SARS-CoV Spike Protein Are More Broadly Neutralizing

text: Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.


docid: vciposnk

title: Clinical differences between respiratory viral and bacterial mono- and dual pathogen detected among Singapore military servicemen with febrile respiratory illness

text: BACKGROUND: Although it is known that febrile respiratory illnesses (FRI) may be caused by multiple respiratory pathogens, there are no population-level studies describing its impact on clinical disease. METHODS: Between May 2009 and October 2012, 7733 FRI patients and controls in the Singapore military had clinical data and nasal wash samples collected prospectively and sent for PCR testing. Patients with one pathogen detected (mono-pathogen) were compared with those with two pathogens (dual pathogen) for differences in basic demographics and clinical presentation. RESULTS: In total, 45.8% had one pathogen detected, 20.2% had two pathogens detected, 30.9% had no pathogens detected, and 3.1% had more than two pathogens. Multiple pathogens were associated with recruits, those with asthma and non-smokers. Influenza A (80.0%), influenza B (73.0%) and mycoplasma (70.6%) were most commonly associated with mono-infections, while adenovirus was most commonly associated with dual infections (62.9%). Influenza A paired with S. pneumoniae had higher proportions of chills and rigors than their respective mono-pathogens (P = 0.03, P = 0.009). H. influenzae paired with either enterovirus or parainfluenzae had higher proportions of cough with phlegm than their respective mono-pathogens. Although there were observed differences in mean proportions of body temperature, nasal symptoms, sore throat, body aches and joint pains between viral and bacterial mono-pathogens, there were few differences between distinct dual-pathogen pairs and their respective mono-pathogen counterparts. CONCLUSION: A substantial number of FRI patients have multiple pathogens detected. Observed clinical differences between patients of dual pathogen and mono-pathogen indicate the likely presence of complex microbial interactions between the various pathogens.


title: Replication of a bovine coronavirus in organ cultures of foetal trachea

text: Abstract A strain of bovine coronavirus (BC) adapted to tissue culture, was inoculated into organ cultures of bovine foetal trachea. Haemagglutinin in the fluid from infected organ cultures reached titres of 32 and characteristic coronavirus particles were observed electron microscopically. BC virus antigen was detected in frozen sections of the organ cultures by staining with fluorescent antibody. These data were evidence that BC virus replicated in organ cultures of respiratory tissue. The use of this technique for primary isolation of bovine coronaviruses from field material is discussed.


title: Association between faecal shedding of feline coronavirus and serum α1-acid glycoprotein sialylation

text: The sialylation pattern of serum α1-acid glycoprotein (AGP) in non-symptomatic cats infected by feline coronavirus (FCoV) and its possible relationship with the amount of FCoVs shed in faeces were investigated. Blood from three specific pathogen-free cats (group A) and from 10 non-symptomatic FCoV-positive cats from catteries with low (group B, three cats) or high (group C, seven cats) levels of faecal shedding were collected monthly. AGP was purified from serum and Western blotting followed by lectin-staining of α(2,3)-linked and α(2,6)-linked sialic acid. Faecal shedding was quantified in group C by quantitative polymerase chain reaction. Variations of AGP sialylation were recorded only in cats from group C, on which viral shedding peaked before the occurrence of feline infectious peritonitis (FIP) in the cattery, and decreased 1 month later, when serum AGP had an increase of α(2,3)-linked sialic acid. These results suggest that hypersialylation of AGP may be involved in host–virus interactions.


title: Therapy of ocular and visceral leishmaniasis in a cat

text: An 8‐year‐old, spayed female Domestic Short‐haired cat was referred for further evaluation of chronic lymphocytic–plasmacytic stomatitis and bilateral ocular disease. The cat had been treated with systemic glucocorticoids for several months. Initial ophthalmic examination revealed bilateral deep stromal corneal ulcers, exudative panuveitis and secondary glaucoma. Mature mild neutrophilia and monocytosis were detected on complete blood cell count. Abnormalities in the serum profile were hyperglycemia, mild azotemia, hyperglobulinemia and moderate polyclonal gammapathy. Urinalysis revealed glucosuria without ketonuria. Diabetes mellitus was diagnosed and treatment with long‐acting insulin was started. An enzyme‐linked immunosorbent assay was highly positive for leishmaniasis, and treatment with allopurinol was started. Although specific topical treatment was applied, melting ulcers progressed to corneal perforation and both eyes were enucleated. Ocular histology showed large numbers of intracellular organisms compatible with amastigotes of the genus Leishmania located in the uveal tract, cornea, sclera and retina. Results of inmunohistochemistry staining on ocular samples were positive for Leishmania. Bone marrow cytology demonstrated numerous macrophages with intracytoplasmatic Leishmania. Polymerase chain reaction results on bone marrow for Leishmania were positive. Three weeks later, hypoglycemic episodes permitted withdrawal of the insulin therapy. To the authors’ knowledge this is the first case of ocular and visceral leishmaniasis diagnosed in vivo and under systemic treatment in a cat.


title: Mouse hepatitis viral infection induces an extrathymic differentiation of the specific intrahepatic alpha beta-TCRintermediate LFA-1high T-cell population.

text: Mouse hepatitis virus type 3 (MHV3), a coronavirus, is an excellent model for the study of thymic and extrathymic T-cell subpopulation disorders induced during viral hepatitis. It was recently reported that, in addition to the intrathymic T-cell differentiation pathway, an extrathymic differentiation pathway of alpha beta-T-cell receptor (TCR) T lymphocytes exists in the liver, and becomes important under pathological situations such as autoimmune diseases, malignancies or hepatic bacterial infections. In the present study, we compared the phenotypes of resident hepatic, splenic or thymic T-cell subpopulations during the acute viral hepatitis induced by HMV3 in susceptible C57BL/6 mice. The number of liver-resident mononuclear cells (MNC) increased during the viral infection, while cellularity decreased. Single positive (SP) CD4+ cells strongly increased in both the liver and thymus, while double positive (DP) (CD4+ CD8+) cells, present in the liver and thymus of mock-infected mice, decreased in C57BL/6 mice during the viral infection. A shift of alpha beta-TCRintermediate T cells toward alpha beta-TCRhigh was evidenced in the liver and thymus of infected mice, but not in the spleen. The few alpha beta-TCRint double negative (DN) (CD4-CD8-) cells also decreased following viral infection. alpha beta-TCRint or high lymphocytes expressing high levels of leucocyte function antigen-1 (LFA-1) increased in the liver of MHV3-infected mice. In addition, liver-resident T cells expressed strongly the CD44 (Pgp-1) activation marker, suggesting that they were either activated or antigen experienced during the viral infection. No significant change in T-cell subpopulations was detected in the spleen, suggesting that MHV3 infection could induce an early in situ differentiation of resident hepatic T cells rather than a recruitment of lymphocytes from peripheral lymphoid organs.


title: Generating stable chinese hamster ovary cell clones to produce a truncated SARS‐CoV spike protein for vaccine development

text: The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS‐CoV) is important for vaccine development. S(TR2) (an 88 kDa truncated SARS‐CoV TW1 S protein carrying the S fragments S‐74‐253, S‐294‐739, and S‐1129‐1255) is capable of expressing a major form of glycoprotein as endo H‐sensitive (∼115 kDa) in CHO cells. To establish stable expressing cell clones, we transfected CHO/dhFr‐cells with the amplifiable vectors ISID (IRES‐driven dhfr) and ISIZ (SV40‐driven dhfr) to select stepwise MTX, and observed enhanced ∼115 kDa glycoform generation through gene amplification. Following stepwise MTX selection, we compared gene amplification levels between two vectors in engineered CHO cell chromosomes. These results confirm that the IRES‐driven dhfr promoter generates greater gene amplification, which in turn enhances S(TR2) expression. Our results indicate that the ∼115 kDa glycoform of S(TR2) protein was capable of increasing after gene amplification. The S(TR2) glycoform did not change between suspension and serum‐free cultures, suggesting that the stable and amplified cell clones analyzed in this study have potential for producing homologous S(TR2) on a large scale. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010


title: Specificity, kinetics and longevity of antibody responses to avian influenza A(H7N9) virus infection in humans

text: Abstract Objectives The long-term dynamics of antibody responses in patients with influenza A(H7N9) virus infection are not well understood. Methods We conducted a longitudinal serological follow-up study in patients who were hospitalized with A(H7N9) virus infection, during 2013–2018. A(H7N9) virus-specific antibody responses were assessed by hemagglutination inhibition (HAI) and neutralization (NT) assays. A random intercept model was used to fit a curve to HAI antibody responses over time. HAI antibody responses were compared by clinical severity. Results Of 67 patients with A(H7N9) virus infection, HAI antibody titers reached 40 on average 11 days after illness onset and peaked at a titer of 290 after three months, and average titers of ≥80 and ≥40 were present until 11 months and 22 months respectively. HAI antibody responses were significantly higher in patients who experienced severe disease, including respiratory failure and acute respiratory distress syndrome, compared with patients who experienced less severe illness. Conclusions Patients with A(H7N9) virus infection who survived severe disease mounted higher antibody responses that persisted for longer periods compared with those that experienced moderate disease. Studies of convalescent plasma treatment for A(H7N9) patients should consider collection of donor plasma from survivors of severe disease between 1 and 11 months after illness onset.


title: Effectiveness of Ribavirin and Corticosteroids for Severe Acute Respiratory Syndrome

text: Abstract Objective Ribavirin and corticosteroids were used widely as front-line treatments for severe acute respiratory syndrome; however, previous evaluations were inconclusive. We assessed the effectiveness of ribavirin and corticosteroids as the initial treatment for severe acute respiratory syndrome using propensity score analysis. Methods We analyzed data on 1755 patients in Hong Kong and 191 patients in Toronto with severe acute respiratory syndrome using a generalized propensity score approach. Results The adjusted excess case fatality ratios of patients with severe acute respiratory syndrome receiving the combined therapy of ribavirin and corticosteroids within 2 days of admission, compared with those receiving neither treatment within 2 days of admission, were 3.8% (95% confidence interval, −1.5 to 9.2) in Hong Kong and 2.1% (95% confidence interval, −44.3 to 48.5) in Toronto. Conclusions Our results add strength to the hypothesis that the combination of ribavirin and corticosteroids has no therapeutic benefit when given early during severe acute respiratory syndrome infection. Further studies may investigate the effects of these treatments later in disease course.


title: Chapter 1 Infection Transmission by Saliva and the Paradoxical Protective Role of Saliva

text: Abstract Saliva is produced by both major (parotid and submandibular and sublingual) and minor (located in the mouth) glands, with different constituents and properties between the two groups. In the mouth saliva is a colorless, odorless, tasteless, watery liquid containing 99% water and 1% organic and inorganic substances and dissolved gases, mainly oxygen and carbon dioxide. Salivary constituents can be grouped into proteins (e.g., amylase and lysozyme), organic molecules (e.g., urea, lipids, and glucose mainly), and electrolytes (e.g., sodium, calcium, chlorine, and phosphates). Cellular elements such as epithelial cells, leukocytes and various hormones, and vitamins have also been detected. The composition of saliva is modified, depending on factors such as secreted amount, circadian rhythm, duration and nature of stimuli, diet, and medication intake, among others.


title: Characterization of SARS-CoV main protease and identification of biologically active small molecule inhibitors using a continuous fluorescence-based assay

text: Severe acute respiratory syndrome associated coronavirus main protease (SARS-CoV M(pro)) has been proposed as a prime target for anti-SARS drug development. We have cloned and overexpressed the SARS-CoV M(pro) in Escherichia coli, and purified the recombinant M(pro) to homogeneity. The kinetic parameters of the recombinant SARS-CoV M(pro) were characterized by high performance liquid chromatography-based assay and continuous fluorescence-based assay. Two novel small molecule inhibitors of the SARS-CoV M(pro) were identified by high-throughput screening using an internally quenched fluorogenic substrate. The identified inhibitors have K(i) values at low μM range with comparable anti-SARS-CoV activity in cell-based assays.


title: Spatial distribution of endemic fluorosis caused by drinking water in a high-fluorine area in Ningxia, China

text: Endemic fluorosis is widespread in China, especially in the arid and semi-arid areas of northwest China, where endemic fluorosis caused by consumption of drinking water high in fluorine content is very common. We analyzed data on endemic fluorosis collected in Ningxia, a typical high-fluorine area in the north of China. Fluorosis cases were identified in 539 villages in 1981, in 4449 villages in 2010, and in 3269 villages in 2017. These were located in 19 administrative counties. In 2017, a total of 1.07 million individuals suffered from fluorosis in Ningxia, with more children suffering from dental fluorosis and skeletal fluorosis. Among Qingshuihe River basin disease areas, the high incidence of endemic fluorosis is in Yuanzhou District and Xiji County of Guyuan City. The paper holds that the genesis of the high incidence of endemic fluorosis in Qingshui River basin is mainly caused by chemical weathering, evaporation and concentration, and dissolution of fluorine-containing rocks around the basin, which is also closely related to the semi-arid geographical region background, basin structure, groundwater chemical characteristics, and climatic conditions of the basin. The process of mutual recharge and transformation between Qingshui River and shallow groundwater in the basin is intense. There is a close coupling relationship between the power of central and southern Ningxia disease areas and Qingshui River watershed of excess fluorine water. Because the traditional drinking water source of the residents in the basin is shallow groundwater, the underground water is the main cause of the high incidence of endemic fluorosis. The results show that Xiji County and Yuanzhou District were the areas of high incidence of endemic fluorosis which gradually decreased to the middle and lower reaches of Qingshui River. In space, distribution characteristics are Qingshui River source area > Qingshui River valley basin area, tributary area > trunk stream area, upstream area > middle reaches area> downstream area of Qingshui River. This is relatively consistent with the spatial distribution of fluoride ion content in Qingshui River groundwater.


title: Cautious handling of urine from moderate to severe COVID-19 patients

text: • SARS-CoV-2 RNA can be detected in patients’ specimens. • The duration and severity of SARS-CoV-2 viral shedding in the urine is currently unknown. • We identified continuous viral shedding in the urine of a severe COVID-19 patient. • Careful handling of urine samples from patients with COVID-19 is recommended.


title: Analysis of the S1 gene of the avian infectious bronchitis virus (IBV) reveals changes in the IBV genetic groups circulating in southern Thailand

text: Abstract The new variants of the avian infectious bronchitis virus (IBV) produce a range of symptoms and cause global economic losses to the poultry industry. We investigated the S1 glycoprotein of 24 recent IBV isolates from chickens and demonstrated that two predominant genetic groups were circulating in southern Thailand between 2008 and 2013. Seven IBV variants, isolated from 2008 to 2009, were clustered in the Thailand THA001 group I while 15 IBV variants, isolated from 2009 to 2013, were classified into the QX-like group II. Moreover, a single isolate from a broiler was categorized into the Massachusetts-type, and an isolate from a layer belonged to the 4/91 type virus. Interestingly, both the IBV groups I and II were isolated from native chickens (62.5%) and caused a range of symptoms. Our results indicate that the QX-like viruses were predominant after 2009, replacing the THA001 type viruses. Furthermore, native chickens may contribute to the epidemiology of IB.


title: Recommendations for treatment of childhood non-severe pneumonia

text: WHO recommendations for early antimicrobial treatment of childhood pneumonia have been effective in reducing childhood mortality, but the last major revision was over 10 years ago. The emergence of antimicrobial resistance, new pneumonia pathogens, and new drugs have prompted WHO to assemble an international panel to review the literature on childhood pneumonia and to develop evidence-based recommendations for the empirical treatment of non-severe pneumonia among children managed by first-level health providers. Treatment should target the bacterial causes most likely to lead to severe disease, including Streptoccocus pneumoniae and Haemophilus influenzae. The best first-line agent is amoxicillin, given twice daily for 3–5 days, although co-trimoxazole may be an alternative in some settings. Treatment failure should be defined in a child who develops signs warranting immediate referral or who does not have a decrease in respiratory rate after 48–72 h of therapy. If failure occurs, and no indication for immediate referral exists, possible explanations for failure should be systematically determined, including non-adherence to therapy and alternative diagnoses. If failure of the first-line agent remains a possible explanation, suitable second-line agents include high-dose amoxicillin–clavulanic acid with or without an affordable macrolide for children over 3 years of age.


title: Investigation of pneumonia-causing pathogenic organisms in children and the usefulness of tebipenem pivoxil for their treatment

text: We investigated the usefulness of the novel oral carbapenem antibiotic tebipenem pivoxil (TBPM-PI) for treating bacterial pneumonia in children. Sputum and nasopharyngeal swabs were collected simultaneously, and causative organisms were identified by conventional bacterial culture together with exhaustive bacterial and viral identification by real-time polymerase chain reaction (PCR). The subjects were eight patients diagnosed with mild or moderate pneumonia at Sotobo Children’s Clinic Outpatient Department between October 2006 and June 2007. TBPM-PI was administered at the recommended clinical dose of 4 mg/kg b.i.d. to five patients and at a high dose of 6 mg/kg b.i.d. to three patients. Sputum was collected from all patients, and 11 strains were detected from washed sputum culture. Causative organisms were mainly Streptococcus pneumoniae (3 strains) and Haemophilus influenzae (6 strains), and nasopharyngeal swabs showed the same organisms as coughed-up sputum. Real-time PCR for individual viruses and Mycoplasma pneumoniae identified four cases of only bacterial infection, one case of M. pneumoniae coinfection, two cases of viral coinfection, and one case of both viral and M. pneumoniae coinfection. The clinical results indicated efficacy in all patients, and causative organisms were 100% eliminated. In the four patients with only bacterial infection, the average fever of 38.9°C at the start of treatment normalized the following day, showing excellent efficacy. No clinically problematic adverse events occurred, and compliance was good. We consider that these cases provide valuable insights into the identity of pathogenic organisms of pneumonia in children and the possible role of TBPM-PI in outpatient treatment.


The Golgi complex: In vitro veritas?


title: Chaos in a nonautonomous eco-epidemiological model with delay

text: Abstract In this paper, we propose and analyze a nonautonomous predator-prey model with disease in prey, and a discrete time delay for the incubation period in disease transmission. Employing the theory of differential inequalities, we find sufficient conditions for the permanence of the system. Further, we use Lyapunov’s functional method to obtain sufficient conditions for global asymptotic stability of the system. We observe that the permanence of the system is unaffected due to presence of incubation delay. However, incubation delay affects the global stability of the positive periodic solution of the system. To reinforce the analytical results and to get more insight into the system’s behavior, we perform some numerical simulations of the autonomous and nonautonomous systems with and without time delay. We observe that for the gradual increase in the magnitude of incubation delay, the autonomous system develops limit cycle oscillation through a Hopf-bifurcation while the corresponding nonautonomous system shows chaotic dynamics through quasi-periodic oscillations. We apply basic tools of non-linear dynamics such as Poincaré section and maximum Lyapunov exponent to confirm the chaotic behavior of the system.


title: The most eagerly awaited summer of the Anthropocene: A perspective of SARS-CoV-2 decay and seasonal change

text: Abstract To date, the world perhaps has never waited for the summer so impatiently in the entire Anthropocene, owing to the debate whether increasing temperature and humidity will decrease the environmental endurance of SARS-CoV-2. We present the perspective on the seasonal change on SARS-CoV-2 decay and COVID-19 spread. Our arguments are based on: i) structural similarity of coronavirus with several enteric viruses, and its vulnerability; ii) reports related to decay of those similar transmissible gastroenteritis viruses (TGEV) like norovirus and iii) improvement in the human immunity during summer with respect to winter. We present reasons why we can be optimistic about the slowdown of corona in the upcoming summer.


title: Alterations in lipid profile in neonatal calves affected by diarrhea

text: AIM: The aim of this study was to determine the alterations in the lipid profile, plasma alkaline phosphatase (ALP) activity, total and direct bilirubin levels of neonatal calves with diarrhea. MATERIALS AND METHODS: A total of 25 calves with diarrhea as experimental group and 10 healthy calves as control group, 1-30 days old, were enrolled in the study. Blood samples were collected from jugular vein in tubes with anticoagulant agent to evaluate the concentration of triglycerides, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), ALP, total and direct bilirubin. Very low-density lipoprotein-cholesterol (VLDL-C) and low-density lipoprotein-cholesterol (LDL-C) levels were calculated according to the Friedewald formula. RESULTS: Significant increases in the plasma levels of ALP (p<0.05), total and direct bilirubin, triglycerides, and VLDL-C (p<0.01) were determined, whereas significant decreases in the levels of total cholesterol, HDL-C and LDL-C (p<0.01) were observed in neonatal calves with diarrhea. CONCLUSION: According to the findings of this study, liver functions impaired and, therefore, lipid profile is affected negatively in neonatal calves with diarrhea.


title: SARS-CoV-2: Is it the newest spark in the TORCH?

text: Abstract Amid the rapidly evolving global coronavirus disease 2019 (COVID-19) pandemic that has already had profound effects on public health and medical infrastructure globally, many questions remain about its impact on child health. The unique needs of neonates and children, and their role in the spread of the virus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) should be included in preparedness and response plans. Fetuses and newborn infants may be uniquely vulnerable to the damaging consequences of congenitally- or perinatally-acquired SARS-CoV-2 infection, but data are limited about outcomes of COVID-19 disease during pregnancy. Therefore, information on illnesses associated with other highly pathogenic coronaviruses (i.e., severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome [MERS]), as well as comparisons to common congenital infections, such as cytomegalovirus (CMV), are warranted. Research regarding the potential routes of acquisition of SARS-CoV-2 infection in the prenatal and perinatal setting is of a high public health priority. Vaccines targeting women of reproductive age, and in particular pregnant patients, should be evaluated in clinical trials and should include the endpoints of neonatal infection and disease.


title: Applications of Gold Nanoparticles in the Detection and Identification of Infectious Diseases and Biothreats

text: The situation of infectious diseases and biothreats all over the world remains serious. The effective identification of such diseases plays a very important role. In recent years, gold nanoparticles have been widely used in biosensor design to improve the performance for the detection of infectious diseases and biothreats. Here, recent advances of gold‐nanoparticle‐based biosensors in this field are summarized.


Pathways to COVID-19 ‘community protection’


title: Lipidation increases antiviral activities of coronavirus fusion-inhibiting peptides

text: Abstract Coronaviruses (CoVs) can cause life-threatening respiratory diseases. Their infectious entry requires viral spike (S) proteins, which attach to cell receptors, undergo proteolytic cleavage, and then refold in a process that catalyzes virus-cell membrane fusion. Fusion-inhibiting peptides bind to S proteins, interfere with refolding, and prevent infection. Here we conjugated fusion-inhibiting peptides to various lipids, expecting this to secure peptides onto cell membranes and thereby increase antiviral potencies. Cholesterol or palmitate adducts increased antiviral potencies up to 1000-fold. Antiviral effects were evident after S proteolytic cleavage, implying that lipid conjugates affixed the peptides at sites of protease-triggered fusion activation. Unlike lipid-free peptides, the lipopeptides suppressed CoV S protein-directed virus entry taking place within endosomes. Cell imaging revealed intracellular peptide aggregates, consistent with their endocytosis into compartments where CoV entry takes place. These findings suggest that lipidations localize antiviral peptides to protease-rich sites of CoV fusion, thereby protecting cells from diverse CoVs.


title: The World Health Organization and Global Health Governance: post-1990

text: Abstract This article takes a historical perspective on the changing position of WHO in the global health architecture over the past two decades. From the early 1990s a number of weaknesses within the structure and governance of the World Health Organization were becoming apparent, as a rapidly changing post Cold War world placed more complex demands on the international organizations generally, but significantly so in the field of global health. Towards the end of that decade and during the first half of the next, WHO revitalized and played a crucial role in setting global health priorities. However, over the past decade, the organization has to some extent been bypassed for funding, and it lost some of its authority and its ability to set a global health agenda. The reasons for this decline are complex and multifaceted. Some of the main factors include WHO's inability to reform its core structure, the growing influence of non-governmental actors, a lack of coherence in the positions, priorities and funding decisions between the health ministries and the ministries overseeing development assistance in several donor member states, and the lack of strong leadership of the organization.


docid: ymddmqkb

title: FIP and coronavirus 7b protein antibodies


Genes & cells: Drug candidate may stop MERS: Chemical disrupts assembly centers of coronaviruses


title: Creating COVID-19 Stigma by Referencing the Novel Coronavirus as the “Chinese virus” on Twitter: Quantitative Analysis of Social Media Data

text: BACKGROUND: Stigma is the deleterious, structural force that devalues members of groups that hold undesirable characteristics. Since stigma is created and reinforced by society—through in-person and online social interactions—referencing the novel coronavirus as the “Chinese virus” or “China virus” has the potential to create and perpetuate stigma. OBJECTIVE: The aim of this study was to assess if there was an increase in the prevalence and frequency of the phrases “Chinese virus” and “China virus” on Twitter after the March 16, 2020, US presidential reference of this term. METHODS: Using the Sysomos software (Sysomos, Inc), we extracted tweets from the United States using a list of keywords that were derivatives of “Chinese virus.” We compared tweets at the national and state levels posted between March 9 and March 15 (preperiod) with those posted between March 19 and March 25 (postperiod). We used Stata 16 (StataCorp) for quantitative analysis, and Python (Python Software Foundation) to plot a state-level heat map. RESULTS: A total of 16,535 “Chinese virus” or “China virus” tweets were identified in the preperiod, and 177,327 tweets were identified in the postperiod, illustrating a nearly ten-fold increase at the national level. All 50 states witnessed an increase in the number of tweets exclusively mentioning “Chinese virus” or “China virus” instead of coronavirus disease (COVID-19) or coronavirus. On average, 0.38 tweets referencing “Chinese virus” or “China virus” were posted per 10,000 people at the state level in the preperiod, and 4.08 of these stigmatizing tweets were posted in the postperiod, also indicating a ten-fold increase. The 5 states with the highest number of postperiod “Chinese virus” tweets were Pennsylvania (n=5249), New York (n=11,754), Florida (n=13,070), Texas (n=14,861), and California (n=19,442). Adjusting for population size, the 5 states with the highest prevalence of postperiod “Chinese virus” tweets were Arizona (5.85), New York (6.04), Florida (6.09), Nevada (7.72), and Wyoming (8.76). The 5 states with the largest increase in pre- to postperiod “Chinese virus” tweets were Kansas (n=697/58, 1202%), South Dakota (n=185/15, 1233%), Mississippi (n=749/54, 1387%), New Hampshire (n=582/41, 1420%), and Idaho (n=670/46, 1457%). CONCLUSIONS: The rise in tweets referencing “Chinese virus” or “China virus,” along with the content of these tweets, indicate that knowledge translation may be occurring online and COVID-19 stigma is likely being perpetuated on Twitter.


COVID‐19, sweat, tears… and myopia?


docid: avhiqlgy

title: Ultra-Low-Dose Chest CT in Patients with Neutropenic Fever and Hematologic Malignancy: Image Quality and Its Diagnostic Performance

text: PURPOSE: The aim of this study was to evaluate the image quality of ultra-low-dose computed tomography (ULDCT) and its diagnostic performance in making a specific diagnosis of pneumonia in febrile neutropenic patients with hematological malignancy. MATERIALS AND METHODS: ULDCT was performed prospectively in 207 febrile neutropenic patients with hematological malignancy. Three observers independently recorded the presence of lung parenchymal abnormality, and also indicated the cause of the lung parenchymal abnormality between infectious and noninfectious causes. If infectious pneumonia was considered the cause of lung abnormalities, they noted the two most appropriate diagnoses among four infectious conditions, including fungal, bacterial, viral, and Pneumocystis pneumonia. Sensitivity for correct diagnoses and receiver operating characteristic (ROC) curve analysis for evaluation of diagnostic accuracy were calculated. Interobserver agreements were determined using intraclass correlation coefficient. RESULTS: Of 207 patients, 139 (67%) had pneumonia, 12 had noninfectious lung disease, and 56 had no remarkable chest computed tomography (CT) (20 with extrathoracic fever focus and 36 with no specific disease). Mean radiation expose dose of ULDCT was 0.60±0.15 mSv. Each observer regarded low-dose CT scans as unacceptable in only four (1.9%), one (0.5%), and three (1.5%) cases of ULDCTs. Sensitivity and area under the ROC curve in making a specific pneumonia diagnosis were 63.0%, 0.65 for reader 1; 63.0%, 0.61 for reader 2; and 65.0%, 0.62 for reader 3; respectively CONCLUSION: ULDCT, with a sub-mSv radiation dose and acceptable image quality, provides ready and reasonably acceptable diagnostic information for pulmonary infection in febrile neutropenic patients with hematologic malignancy


title: A secure location-based alert system with tunable privacy-performance trade-off

text: Monitoring location updates from mobile users has important applications in many areas, ranging from public health (e.g., COVID-19 contact tracing) and national security to social networks and advertising. However, sensitive information can be derived from movement patterns, thus protecting the privacy of mobile users is a major concern. Users may only be willing to disclose their locations when some condition is met, for instance in proximity of a disaster area or an event of interest. Currently, such functionality can be achieved using searchable encryption. Such cryptographic primitives provide provable guarantees for privacy, and allow decryption only when the location satisfies some predicate. Nevertheless, they rely on expensive pairing-based cryptography (PBC), of which direct application to the domain of location updates leads to impractical solutions. We propose secure and efficient techniques for private processing of location updates that complement the use of PBC and lead to significant gains in performance by reducing the amount of required pairing operations. We implement two optimizations that further improve performance: materialization of results to expensive mathematical operations, and parallelization. We also propose an heuristic that brings down the computational overhead through enlarging an alert zone by a small factor (given as system parameter), therefore trading off a small and controlled amount of privacy for significant performance gains. Extensive experimental results show that the proposed techniques significantly improve performance compared to the baseline, and reduce the searchable encryption overhead to a level that is practical in a computing environment with reasonable resources, such as the cloud.


title: Human Neural Precursor Cells Promote Neurologic Recovery in a Viral Model of Multiple Sclerosis

text: Using a viral model of the demyelinating disease multiple sclerosis (MS), we show that intraspinal transplantation of human embryonic stem cell-derived neural precursor cells (hNPCs) results in sustained clinical recovery, although hNPCs were not detectable beyond day 8 posttransplantation. Improved motor skills were associated with a reduction in neuroinflammation, decreased demyelination, and enhanced remyelination. Evidence indicates that the reduced neuroinflammation is correlated with an increased number of CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) within the spinal cords. Coculture of hNPCs with activated T cells resulted in reduced T cell proliferation and increased Treg numbers. The hNPCs acted, in part, through secretion of TGF-β1 and TGF-β2. These findings indicate that the transient presence of hNPCs transplanted in an animal model of MS has powerful immunomodulatory effects and mediates recovery. Further investigation of the restorative effects of hNPC transplantation may aid in the development of clinically relevant MS treatments.


title: Cellular evasion strategies of Helicobacter pylori in regulating its intracellular fate

text: Abstract Helicobacter pylori colonizes human stomach mucosa and its infection causes gastrointestinal diseases with variable severity. Bacterial infection stimulates autophagy, which is a part of innate immunity used to eliminate intracellular pathogens. Several intracellular bacteria have evolved multipronged strategies to circumvent this conserved system and thereby enhance their chance of intracellular survival. Nonetheless, studies on H. pylori have produced inconsistent results, showing either elevated or reduced clearance efficiency of intracellular bacteria through autophagy. In this review, we summarize recent studies on the mechanisms involved in autophagy induced by H. pylori and the fate of intracellular bacteria.


title: Adverse effects of isolation in hospitalised patients: a systematic review

text: Summary The use of transmission precautions such as contact isolation in patients known to be colonised or infected with multidrug-resistant organisms is recommended in healthcare institutions. Although essential for infection control, contact isolation has recently been associated with adverse effects in patients. We undertook a systematic review to determine whether contact isolation leads to psychological or physical problems for patients. Studies were included if (1) hospitalised patients were placed under isolation precautions for an underlying medical indication, and (2) any adverse events related to the isolation were evaluated. We found 16 studies that reported data regarding the impact of isolation on patient mental well-being, patient satisfaction, patient safety or time spent by healthcare workers in direct patient care. The majority showed a negative impact on patient mental well-being and behaviour, including higher scores for depression, anxiety and anger among isolated patients. A few studies also found that healthcare workers spent less time with patients in isolation. Patient satisfaction was adversely affected by isolation if patients were kept uninformed of their healthcare. Patient safety was also negatively affected, leading to an eight-fold increase in adverse events related to supportive care failures. We found that contact isolation may negatively impact several dimensions of patient care. Well-validated tools are necessary to investigate these results further. Large studies examining a number of safety indicators to assess the adverse effects of isolation are needed. Patient education may be an important step to mitigate the adverse psychological effects of isolation and is recommended.


title: IFN-λ4 is associated with increased risk and earlier occurrence of gastrointestinal, respiratory and malarial infections in Malian children

text: Genetic polymorphisms within the IFNL3/IFNL4 genomic region, which encodes type III interferons, have been strongly associated with impaired clearance of hepatitis C virus (HCV) infection. We hypothesized that type III interferons might be important for the immune response to other pathogens as well. In a cohort of 914 Malian children, we analyzed episodes of malaria, gastrointestinal and respiratory infections using information for 30,626 clinic visits from birth through up to 5 years of follow-up. Genetic polymorphisms IFNL4-rs368234815 and IFNL3-rs4803217 that functionally affect type III interferons were genotyped with TaqMan assays. For both genetic variants and each infection, we evaluated time-to-first episode and calculated odds ratios (ORs) for the risk of an infection episode during follow-up, controlling for relevant covariates. Compared to children with the rs368234815-TT/TT genotype (IFN-λ4-Null), each copy of the rs368234815-dG allele was associated with an earlier first episode of a gastrointestinal infection (p=0.003) and respiratory infection (p=0.045). The risk of experiencing an infection episode during the follow-up was also significantly increased with each copy of the rs368234815-dG allele – for gastrointestinal infections (OR=1.53, 95%CI (1.13-2.07), p=0.005) and malaria (OR=1.30, 95%CI (1.02-1.65), p=0.033). IFNL4-rs368234815 and IFNL3-rs4803217 were in moderate linkage disequilibrium in this population (r2=0.78), and all the associations for rs4803217 were weaker and lost significance after adjusting for rs368234815, implicating IFN-λ4 and not IFN-λ3 as the primary cause of these associations. We conclude that the ability to produce IFN-λ4 may have broad health-related implications by negatively affecting the immune response and clinical outcomes of several common infections.


title: SSW Library: An SIMD Smith-Waterman C/C++ Library for Use in Genomic Applications

text: BACKGROUND: The Smith-Waterman algorithm, which produces the optimal pairwise alignment between two sequences, is frequently used as a key component of fast heuristic read mapping and variation detection tools for next-generation sequencing data. Though various fast Smith-Waterman implementations are developed, they are either designed as monolithic protein database searching tools, which do not return detailed alignment, or are embedded into other tools. These issues make reusing these efficient Smith-Waterman implementations impractical. RESULTS: To facilitate easy integration of the fast Single-Instruction-Multiple-Data Smith-Waterman algorithm into third-party software, we wrote a C/C++ library, which extends Farrar’s Striped Smith-Waterman (SSW) to return alignment information in addition to the optimal Smith-Waterman score. In this library we developed a new method to generate the full optimal alignment results and a suboptimal score in linear space at little cost of efficiency. This improvement makes the fast Single-Instruction-Multiple-Data Smith-Waterman become really useful in genomic applications. SSW is available both as a C/C++ software library, as well as a stand-alone alignment tool at: https://github.com/mengyao/Complete-Striped-Smith-Waterman-Library. CONCLUSIONS: The SSW library has been used in the primary read mapping tool MOSAIK, the split-read mapping program SCISSORS, the MEI detector TANGRAM, and the read-overlap graph generation program RZMBLR. The speeds of the mentioned software are improved significantly by replacing their ordinary Smith-Waterman or banded Smith-Waterman module with the SSW Library.


Essais cliniques en période de pandémie: garantir la sécurité des patients et maintenir l’accès à l’innovation


docid: tweqxttb

title: Neutrophil calprotectin identifies severe pulmonary disease in COVID-19

text: Severe cases of coronavirus disease 2019 (COVID-19) are regularly complicated by respiratory failure. While it has been suggested that elevated levels of blood neutrophils associate with worsening oxygenation in COVID-19, it is unknown whether neutrophils are drivers of the thrombo-inflammatory storm or simple bystanders. We now report that patients with COVID-19 (n=96) have markedly elevated levels of the neutrophil activation marker S100A8/A9 (calprotectin) in their blood. Calprotectin tracked with other acute phase reactants including C-reactive protein, D-dimer, ferritin, and absolute neutrophil count, but was superior in identifying patients requiring mechanical ventilation. In longitudinal samples, calprotectin rose as oxygenation worsened. When tested on day 1 or 2 of hospitalization (n=52 patients), calprotectin levels were significantly higher in patients who progressed to severe COVID-19 requiring mechanical ventilation (7805 +/- 7585, n=23) as compared to those who remained free of intubation (3123 +/- 2990, p=0.0059). In summary, serum calprotectin levels track closely with current and future COVID-19 severity, strongly implicating neutrophils as active perpetuators of inflammation and respiratory compromise in COVID-19.


title: Delivering extracorporeal membrane oxygenation for patients with COVID‐19: what, who, when and how?

text: On 11 March 2020, the World Health Organization (WHO) declared novel coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus-2 (SARS-CoV-2), a worldwide pandemic. Although most patients with SARS-CoV-2 are asymptomatic or experience only mild disease, approximately 14% develop severe disease associated with a high case fatality rate [1-3]. Patients with severe respiratory failure refractory to tracheal intubation, positive pressure ventilation, prone positioning, deep sedation, neuromuscular blockade and other conventional strategies might be considered for venovenous extracorporeal membrane oxygenation (VV-ECMO).


title: Marine Sponges as Pharmacy

text: Marine sponges have been considered as a gold mine during the past 50 years, with respect to the diversity of their secondary metabolites. The biological effects of new metabolites from sponges have been reported in hundreds of scientific papers, and they are reviewed here. Sponges have the potential to provide future drugs against important diseases, such as cancer, a range of viral diseases, malaria, and inflammations. Although the molecular mode of action of most metabolites is still unclear, for a substantial number of compounds the mechanisms by which they interfere with the pathogenesis of a wide range of diseases have been reported. This knowledge is one of the key factors necessary to transform bioactive compounds into medicines. Sponges produce a plethora of chemical compounds with widely varying carbon skeletons, which have been found to interfere with pathogenesis at many different points. The fact that a particular disease can be fought at different points increases the chance of developing selective drugs for specific targets.


Incidental SARS-CoV-2-related findings in asymptomatic patients in [(18)F]-FDG-PET/CT—potential insights


title: Comparison of 9 different PCR primers for the rapid detection of severe acute respiratory syndrome coronavirus using 2 RNA extraction methods

text: Abstract The sensitivity and specificity of various severe acute respiratory syndrome coronavirus (SARS-CoV) PCR primer and probe sets were evaluated through the use of commercial kits and in-house amplification formats. Conventional and real-time PCR assays were performed using a heat-block thermocycler ABI 9600, the Roche LightCycler™ version 1.2, or the ABI 7000 Sequence Detection System. The sensitivity of all primers was between 0.0004 and 0.04 PFU with viral cell lysate and between 0.004 and 0.4 PFU in spiked stool specimen per PCR assay. The primer sets for real-time PCR assays were at one least 1 log more sensitive than the primer sets used in the conventional PCR. A panel of viruses including swine gastroenteritis virus, bovine coronavirus, avian bronchitis virus (Connecticut strain), avian bronchitis virus (Massachusetts strain), human coronaviruses 229E and OC43, parainfluenza virus (type III), human metapneumovirus, adenovirus, respiratory syncytial virus, and influenza A were tested by all assays. All real-time PCR assays used probe-based detection, and no cross-reactivity was observed. With conventional PCR, analysis was performed using agarose gel electrophoresis and multiple nonspecific bands were observed. Two commercial extraction methods, magnetic particle capture and silica-based procedure were evaluated and the results were comparable. The former was less laborious with shorter time for completion and can easily be adapted to an automated system such as the MagNa Pure-LC, which can extract nucleic acid from clinical samples and load it into the sample capillaries of the LightCycler™. As exemplified by this study, the continued refinement and evaluation of PCR procedures will greatly benefit the diagnostic laboratory during an outbreak of SARS.


title: Clear communication helps with transition to online learning

text: Tracey Forman, Assistant Director of Disability Resources at Texas A&M University, led an effort to share information students with disabilities needed during the rapid move to online instruction resulting from the COVID‐19 pandemic. She shared her unit's process for creating resources.


title: Patients with Sickle cell disease and suspected COVID‐19 in a pediatric ICU

text: Concern has been raised on sickle cell disease (SCD) patients and the new viral infection with SARS‐COV‐2 since SCD patients are particularly prone to infectious diseases and acute chest syndrome (ACS). Although case reports have been published to describe COVID‐19 related ACS in adult patients (1–4), pediatric data are lacking.


title: Recombination in viruses: Mechanisms, methods of study, and evolutionary consequences

text: Abstract Recombination is a pervasive process generating diversity in most viruses. It joins variants that arise independently within the same molecule, creating new opportunities for viruses to overcome selective pressures and to adapt to new environments and hosts. Consequently, the analysis of viral recombination attracts the interest of clinicians, epidemiologists, molecular biologists and evolutionary biologists. In this review we present an overview of three major areas related to viral recombination: (i) the molecular mechanisms that underlie recombination in model viruses, including DNA-viruses (Herpesvirus) and RNA-viruses (Human Influenza Virus and Human Immunodeficiency Virus), (ii) the analytical procedures to detect recombination in viral sequences and to determine the recombination breakpoints, along with the conceptual and methodological tools currently used and a brief overview of the impact of new sequencing technologies on the detection of recombination, and (iii) the major areas in the evolutionary analysis of viral populations on which recombination has an impact. These include the evaluation of selective pressures acting on viral populations, the application of evolutionary reconstructions in the characterization of centralized genes for vaccine design, and the evaluation of linkage disequilibrium and population structure.


Correction to Lancet Infect Dis 2020; Published online March 23, 2020 https://doi.org/10.1016/S1473-3099(20)30226-7


docid: bcxkycjh

title: Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks

text: BACKGROUND: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. METHODS: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. RESULTS: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. CONCLUSIONS: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.


Comment on “Dermatology Residents and the Care of COVID-19 Patients”


docid: uwioxloc

title: COVID-19 Pandemic along with Pandemic of Lifestyle-Associated Diseases Victimizes Patients in an Inflammation Context!


title: Porcine parvovirus VP1/VP2 on a time series epitope mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens

text: Porcine parvovirus (PPV) is a DNA virus that causes reproductive failure in gilts and sows, resulting in embryonic and fetal losses worldwide. Epitope mapping of PPV is important for developing new vaccines. In this study, we used spot synthesis analysis for epitope mapping of the capsid proteins of PPV (NADL-2 strain) and correlated the findings with predictive data from immunoinformatics. The virus was exposed to three conditions prior to inoculation in pigs: native (untreated), high hydrostatic pressure (350 MPa for 1 h) at room temperature and high hydrostatic pressure (350 MPa for 1 h) at − 18 °C, and was compared with a commercial vaccine produced using inactivated PPV. The screening of serum samples detected 44 positive spots corresponding to 20 antigenic sites. Each type of inoculated antigen elicited a distinct epitope set. In silico prediction located linear and discontinuous epitopes in B cells that coincided with several epitopes detected in spot synthesis of sera from pigs that received different preparations of inoculum. The conditions tested elicited antibodies against the VP1/VP2 antigen that differed in relation to the response time and the profile of structurally available regions that were recognized. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-019-1165-1) contains supplementary material, which is available to authorized users.


title: Evidence of human coronavirus HKU1 and human bocavirus in Australian children

text: Abstract Undiagnosed cases of respiratory tract disease suspected of an infectious aetiology peak during the winter months. Since studies applying molecular diagnostic assays usually report reductions in the number of undiagnosed cases of infectious disease compared to traditional techniques, we applied PCR assays to investigate the role of two recently described viruses, namely human coronavirus (HCoV) HKU1 and human bocavirus (HBoV), in a hospital-based paediatric population. Both viruses were found among Australia children with upper or lower respiratory tract disease during the autumn and winter of 2004, contributing to 21.1% of all microbial diagnoses, with individual incidences of 3.1% (HCoV-HKU1) and 5.6% (HBoV) among 324 specimens. HBoV was found to coincide with another virus in more than half of all instances and displayed a single genetic lineage, whilst HCoV-HKU1 was more likely to occur in the absence of another microbe and strains could be divided into two genetic lineages which we propose be termed HCoV-HKU1 type A and type B. Children under the age of 2 years were most at risk of infection by these viruses which contribute significantly to the microbial burden among patients with respiratory tract disease during the colder months.


title: Nasal Swab Sampling for SARS-CoV-2: a Convenient Alternative in Times of Nasopharyngeal Swab Shortage

text: Nasopharyngeal swab is the reference sampling method to detect SARS CoV2, as recommended by world Health Organization (WHO) (1).….


title: Using Social Media and Technology to Communicate in Pediatric HIV Research: Qualitative Study With Young Adults Living With or Exposed to Perinatal HIV

text: BACKGROUND: As young adults living with perinatal HIV (PHIV) or perinatal HIV exposure but uninfected (PHEU) grow older and manage the challenges and competing demands of young adulthood, new approaches are needed to facilitate their retention in longitudinal research and clinical care beyond in-person clinic visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel virus that causes coronavirus disease (COVID-19), emerged in the United States in January 2020 and has underscored this need; studies are adapting to remote communication with and data collection from participants. However, there are limited data on communication preferences among young adults who are living with PHIV or PHEU. OBJECTIVE: The objectives of this qualitative study were to describe participants’ perceptions and use of social media and technology in their personal lives and in the context of participating in longitudinal pediatric HIV research and to describe the implications of the use of technology and social media for communication and retention purposes within a longitudinal pediatric study about HIV. METHODS: We conducted 6 focus group discussions with 31 young adults living with PHIV and 13 in-depth interviews with 6 young adults living with PHIV and 7 living with PHEU. We asked about their preferences for the use of social media and digital technology in the Adolescent Master Protocol, a US-based longitudinal cohort study of youth affected by HIV. RESULTS: Participants’ willingness to use social media platforms, telephone calls, SMS text messages, and video calls within the context of HIV research varied due to fears of HIV stigma and inadvertent disclosure. However, trusting relationships with clinical staff positively impacted their willingness to use these platforms. CONCLUSIONS: Our findings offer insight into how pediatric studies and clinics can communicate with participants as they age, even as new technologies and social media platforms emerge and replace old ones. For optimal retention, pediatric clinical staff should consider communication approaches offering flexible and tailored options for young adults participating in HIV research.


title: Induction and suppression of innate antiviral responses by picornaviruses

text: Abstract The family Picornaviridae comprises of small, non-enveloped, positive-strand RNA viruses and contains many human and animal pathogens including enteroviruses (e.g. poliovirus, coxsackievirus, enterovirus 71 and rhinovirus), cardioviruses (e.g. encephalomyocarditis virus), hepatitis A virus and foot-and-mouth disease virus. Picornavirus infections activate a cytosolic RNA sensor, MDA5, which in turn, induces a type I interferon response, a crucial component of antiviral immunity. Moreover, picornaviruses activate the formation of stress granules (SGs), large aggregates of preassembled mRNPs (messenger ribonucleoprotein particles) to temporarily store these molecules upon cellular stress. Meanwhile, picornaviruses actively suppress these antiviral responses to ensure efficient replication. In this review we provide an overview of the induction and suppression of the MDA5-mediated IFN-α/β response and the cellular stress pathway by picornaviruses.


title: 2015 MERS outbreak in Korea: hospital-to-hospital transmission

text: The distinct characteristic of the Middle East Respiratory Syndrome (MERS) outbreak in South Korea is that it not only involves intra-hospital transmission, but it also involves hospital-to-hospital transmission. It has been the largest MERS outbreak outside the Middle East, with 186 confirmed cases and, among them, 36 fatal cases as of July 26, 2015. All confirmed cases are suspected to be hospital-acquired infections except one case of household transmission and two cases still undergoing examination. The Korean health care system has been the major factor shaping the unique characteristics of the outbreak. Taking this as an opportunity, the Korean government should carefully assess the fundamental problems of the vulnerability to hospital infection and make short- as well as long-term plans for countermeasures. In addition, it is hoped that this journal, Epidemiology and Health, becomes a place where various topics regarding MERS can be discussed and shared.


title: A review of coccidiosis in South American camelids

text: Camelids (llamas, alpacas, vicuñas, guanacos) are important for the economy of South America and Eimeria infections are important as cause of mortality in camelids. Of the five most prevalent species of Eimeria in South American camelids, Eimeria macusaniensis, Eimeria lamae, Eimeria alpacae, Eimeria punoensis, and Eimeria ivitaensis, E. macusaniensis is considered the most pathogenic. There is considerable confusion concerning the endogenous developmental stages of Eimeria spp. in camelids. Many papers on camelid coccidiosis were published in local Peruvian journals, not easily accessible to wider audience. The objective of the present paper is to summarize information on history, validity of Eimeria species, life cycle, pathogenicity, prevalence, epidemiology, diagnosis, and control of coccidiosis in camelids.


If Everything Has Changed, Why Such a Focus on Bailing Out Capitalism? The Somber Reality Underpinning Covid-19


title: COVID-19 Virulence in Aged Patients Might Be Impacted by the Host Cellular MicroRNAs Abundance/Profile

text: The World health organization (WHO) declared Coronavirus disease 2019 (COVID-19) a global pandemic and a severe public health crisis. Drastic measures to combat COVID-19 are warranted due to its contagiousness and higher mortality rates, specifically in the aged patient population. At the current stage, due to the lack of effective treatment strategies for COVID-19 innovative approaches need to be considered. It is well known that host cellular miRNAs can directly target both viral 3'UTR and coding region of the viral genome to induce the antiviral effect. In this study, we did in silico analysis of human miRNAs targeting SARS (4 isolates) and COVID-19 (29 recent isolates from different regions) genome and correlated our findings with aging and underlying conditions. We found 848 common miRNAs targeting the SARS genome and 873 common microRNAs targeting the COVID-19 genome. Out of a total of 848 miRNAs from SARS, only 558 commonly present in all COVID-19 isolates. Interestingly, 315 miRNAs are unique for COVID-19 isolates and 290 miRNAs unique to SARS. We also noted that out of 29 COVID-19 isolates, 19 isolates have identical miRNA targets. The COVID-19 isolates, Netherland (EPI_ISL_422601), Australia (EPI_ISL_413214), and Wuhan (EPI_ISL_403931) showed six, four, and four unique miRNAs targets, respectively. Furthermore, GO, and KEGG pathway analysis showed that COVID-19 targeting human miRNAs involved in various age-related signaling and diseases. Recent studies also suggested that some of the human miRNAs targeting COVID-19 decreased with aging and underlying conditions. GO and KEGG identified impaired signaling pathway may be due to low abundance miRNA which might be one of the contributing factors for the increasing severity and mortality in aged individuals and with other underlying conditions. Further, in vitro and in vivo studies are needed to validate some of these targets and identify potential therapeutic targets.


title: Differential localization and turnover of infectious bronchitis virus 3b protein in mammalian versus avian cells

text: Abstract Infectious bronchitis virus (IBV) 3b protein is highly conserved among group 3 coronaviruses, suggesting that it is important for infection. A previous report (Virology 2003, 311:16–27) indicated that transfected IBV 3b localized to the nucleus in mammalian cells using a vaccinia-virus expression system. Although we confirmed these findings, we observed cytoplasmic localization of IBV 3b with apparent exclusion from the nucleus in avian cells (IBV normally infects chickens). IBV 3b was virtually undetectable by microscopy in mammalian cells transfected without vaccinia virus and in IBV-infected mammalian cells because of a greatly reduced half-life in these cells. A proteasome inhibitor stabilized IBV 3b in mammalian cells, but had little effect on IBV 3b in avian cells, suggesting that rapid turnover of IBV 3b in mammalian cells is proteasome-dependent while turnover in avian cells may be proteasome-independent. Our results highlight the importance of using cells derived from the natural host when studying coronavirus non-structural proteins.


title: Setting realistic goals for feeding infants when their mothers have suspected or confirmed COVID‐19

text: The pandemic is a stressful time for everyone, including mothers and healthcare providers who are concerned about the best and safest way to feed babies born to mothers with suspected or confirmed COVID‐19. There is lack of consensus regarding mother‐infant contact, unless the mother definitely has COVID‐19 and even then there is a distinct lack of data to devise protocols for everyday clinical practice.(1,2)


title: Syndromic Surveillance: Hospital Emergency Department Participation During the Kentucky Derby Festival

text: Introduction Electronic syndromic surveillance may have value in detecting emerging pathogens or a biological weapons release. Hospitals that have an agile process to evaluate chief complaints of patients seeking emergency care may be able to more quickly identify subtle changes in the community's health. An easily adaptable prototype system was developed to monitor emergency department patient visits during the Kentucky Derby Festival in Louisville, Kentucky, from April 16–May 14, 2002. Use of the system was continued during the same festival periods in 2003 and 2004. Method Twelve area hospitals in Louisville, Kentucky, participated in a prospective analysis of the chief symptoms of patients who sought care in the emergency department during the Kentucky Derby Festival during 2002. Six hospitals were classified as computer record groups (CRG) and used their existing computerized record capabilities. The other 6 hospitals used a personal digital assistant (PDA) with customized software (PDA group). Data were evaluated by the health department epidemiologist using SaTScan, a modified version of a cancer cluster detection program, to look for clusters of cases above baseline over time and by Zip code. Results All 12 hospitals were able to collect and provide data elements during the study period. The 6 CRG hospitals were able to perform daily data transmission; however, 3 CRG hospitals were unable to interpret their data because it was transmitted in pure text format. In contrast, data from all 6 PDA group hospitals were interpretable. Real-time data analysis was compared with postevent data, and it was found that the real-time evaluation correctly identified no unusual disease activity during the study period. Conclusions The 12 hospitals participating in this study demonstrated that community-wide surveillance using computerized data was possible and that the 6 study hospitals using a PDA could quickly interpret emergency department patients' chief complaints. The emergency department chief complaints group could serve as a disease sentinel for the community.


title: The nucleocapsid proteins of mouse hepatitis virus and severe acute respiratory syndrome coronavirus share the same IFN-β antagonizing mechanism: attenuation of PACT-mediated RIG-I/MDA5 activation

text: Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5). Further studies showed that both MHV and SARS-CoV N proteins directly interacted with protein activator of protein kinase R (PACT), a cellular dsRNA-binding protein that can bind to RIG-I and MDA5 to activate IFN production. The N–PACT interaction sequestered the association of PACT and RIG-I/MDA5, which in turn inhibited IFN-β production. However, the N proteins from porcine epidemic diarrhea virus (PEDV) and porcine reproductive and respiratory syndrome virus (PRRSV), which are also classified in the order Nidovirales, did not interact and counteract with PACT. Taken together, our present study confirms that both MHV and SARS-CoV N proteins can perturb the function of cellular PACT to circumvent the innate antiviral response. However, this strategy does not appear to be used by all CoVs N proteins.


title: Containing the spread of coronavirus disease 2019 (COVID-19): Meteorological factors and control strategies

text: Abstract The novel coronavirus disease 2019 (COVID-19) has spread globally and the meteorological factors vary greatly across the world. Understanding the effect of meteorological factors and control strategies on COVID-19 transmission is critical to contain the epidemic. Using individual-level data in mainland China, Hong Kong, and Singapore, and the number of confirmed cases in other regions, we explore the effect of temperature, relative humidity, and control measures on the spread of COVID-19. We find that high temperature mitigates the transmission of the disease. High relative humidity promotes COVID-19 transmission when temperature is low, but tends to reduce transmission when temperature is high. Implementing classical control measures can dramatically slow the spread of the disease. However, due to the occurrence of pre-symptomatic infections, the effect of the measures to shorten treatment time is markedly reduced and the importance of contact quarantine and social distancing increases.


title: An Aberration Detection-Based Approach for Sentinel Syndromic Surveillance of COVID-19 and Other Novel Influenza-Like Illnesses

text: Coronavirus Disease 2019 (COVID-19) has emerged as a significant global concern, triggering harsh public health restrictions in a successful bid to curb its exponential growth. As discussion shifts towards relaxation of these restrictions, there is significant concern of second-wave resurgence. The key to managing these outbreaks is early detection and intervention, and yet there is significant lag time associated with usage of laboratory confirmed cases for surveillance purposes. To address this, syndromic surveillance can be considered to provide a timelier alternative for first-line screening. Existing syndromic surveillance solutions are however typically focused around a known disease and have limited capability to distinguish between outbreaks of individual diseases sharing similar syndromes. This poses a challenge for surveillance of COVID-19 as its active periods are tend to overlap temporally with other influenza-like illnesses. In this study we explore performing sentinel syndromic surveillance for COVID-19 and other influenza-like illnesses using a deep learning-based approach. Our methods are based on aberration detection utilizing autoencoders that leverages symptom prevalence distributions to distinguish outbreaks of two ongoing diseases that share similar syndromes, even if they occur concurrently. We first demonstrate that this approach works for detection of outbreaks of influenza, which has known temporal boundaries. We then demonstrate that the autoencoder can be trained to not alert on known and well-managed influenza-like illnesses such as the common cold and influenza. Finally, we applied our approach to 2019–2020 data in the context of a COVID-19 syndromic surveillance task to demonstrate how implementation of such a system could have provided early warning of an outbreak of a novel influenza-like illness that did not match the symptom prevalence profile of influenza and other known influenza-like illnesses.


Falsely Low Fibrinogen Levels in COVID-19 Patients on Direct Thrombin Inhibitors


title: Development and in vitro evaluation of chloroquine gels as microbicides against HIV-1 infection

text: Abstract The potential success of a microbicide candidate in resource-poor countries will depend to a large extent on its availability and cost. Chloroquine is an inexpensive antimalarial drug that also exerts anti-HIV activity. The purpose of this study was to develop and characterize a vaginal formulation for chloroquine with preservation of its anti-HIV-1 activity. Gels containing the nonionic polymer hydroxyethyl cellulose were loaded with concentrations of the diphosphate salt of chloroquine (0.3–30 mg/g), that were 102- to 104-fold higher than typical in vitro anti-HIV-1 IC50-values of chloroquine (ca. 6 μg/ml). The gels were clear and homogeneous and displayed an osmolality of 300 mOsm/kg, a pH of 4.6 and a viscosity of 1.4 Pa s. Gel characteristics were preserved for at least 3 months at 40 °C and 75% relative humidity. Importantly, the chloroquine gels exerted a dose-dependent anti-HIV-1 activity in vitro (mean IC50 from 23 to 0.4 mg gel/ml) and the intrinsic activity of chloroquine was not affected by formulation factors. The in vitro efficacy of the chloroquine gel formulations warrants further testing of this drug as an anti-HIV-1 microbicide candidate.


For the life after COVID-19 pandemic – A gynecologist’s call to action


COVID 19 and low-glucose levels : is there a link ?


On the molecular determinants the SARS-CoV-2 attack


title: Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

text: Abstract Nucleos(t)ide analogues play pivotal roles as antiviral, cytotoxic or immunosuppressive agents. Here, we review recent reports of nucleoside analogues that exhibit broad-spectrum activity towards multiple life-threatening RNA and DNA viruses. We also present a discussion about nucleoside antimetabolites—approved antineoplastic agents—that have recently been shown to have antiviral and/or antibacterial activity. The approved drugs and drug combinations, as well as recently identified candidates for investigation and/or experimentation, are discussed. Several examples of repurposed drugs that have already been approved for use are presented. This strategy can be crucial for the first-line treatment of acute infections or coinfections and for the management of drug-resistant strains.


title: Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?

text: PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.


title: Methodology for assessment of public health emergency preparedness and response synergies between institutional authorities and communities

text: BACKGROUND: This paper describes a participatory methodology that supports investigation of the synergistic collaboration between communities affected by infectious disease outbreak events and relevant official institutions. The core principle underlying the methodology is the recognition that synergistic relationships, characterised by mutual trust and respect, between affected communities and official institutions provide the most effective means of addressing outbreak situations. METHODS: The methodological approach and lessons learned were derived from four qualitative case studies including (i) two tick-borne disease events (Crimean-Congo haemorrhagic fever in Spain, 2016, and tick-borne encephalitis in the Netherlands, 2016); and (ii) two outbreaks of acute gastroenteritis (norovirus in Iceland, 2017, and verocytotoxin-producing Escherichia coli [VTEC] in Ireland, 2018). An after-event qualitative case study approach was taken using mixed methods. The studies were conducted in collaboration with the respective national public health authorities in the affected countries by the European Centre for Disease Prevention and Control (ECDC). The analysis focused on the specific actions undertaken by the participating countries’ public health and other authorities in relation to community engagement, as well as the view from the perspective of affected communities. RESULTS: Lessons highlight the critical importance of collaborating with ECDC National Focal Points during preparation and planning and with anthropological experts. Field work for each case study was conducted over one working week, which although limiting the number of individuals and institutions involved, still allowed for rich data collection due to the close collaboration with local authorities. The methodology enabled efficient extraction of synergies between authorities and communities. Implementing the methodology required a reflexivity among fieldworkers that ackowledges that different versions of reality can co-exist in the social domain. The method allowed for potential generalisability across studies. Issues of extra attention included insider-outsider perspectives, politically sensitivity of findings, and how to deal with ethical and language issues. CONCLUSIONS: The overall objective of the assessment is to identify synergies between institutional decision-making bodies and community actors and networks before, during and after an outbreak response to a given public health emergency. The methodology is generic and could be applied to a range of public health emergencies, zoonotic or otherwise.


title: Feline Virome—A Review of Novel Enteric Viruses Detected in Cats

text: Recent advances in the diagnostic and metagenomic investigations of the feline enteric environment have allowed the identification of several novel viruses that have been associated with gastroenteritis in cats. In the last few years, noroviruses, kobuviruses, and novel parvoviruses have been repetitively detected in diarrheic cats as alone or in mixed infections with other pathogens, raising a number of questions, with particular regards to their pathogenic attitude and clinical impact. In the present article, the current available literature on novel potential feline enteric viruses is reviewed, providing a meaningful update on the etiology, epidemiologic, pathogenetic, clinical, and diagnostic aspects of the infections caused by these pathogens.


title: Structural Flexibility of the Pentameric SARS Coronavirus Envelope Protein Ion Channel

text: Coronaviruses contain a small envelope membrane protein with cation-selective ion channel activity mediated by its transmembrane domain (ETM). In a computational study, we proposed that ion channel activity can be explained by either of two similar ETM homopentameric transmembrane α-helical bundles, related by a ∼50° rotation of the helices. Later, we tested this prediction, using site-specific infrared dichroism of a lysine-flanked isotopically labeled ETM peptide from the virus responsible for the severe acute respiratory syndrome, SARS, reconstituted in lipid bilayers. However, the data were consistent with the presence of a kink at the center of the ETM α-helix, and it did not fit completely either computational model. Herein, we have used native ETM, without flanking lysines, and show that the helix orientation is now consistent with one of the predicted models. ETM only produced one oligomeric form, pentamers, in the lipid-mimic detergent dodecylphosphocholine and in perfluorooctanoic acid. We thus report the correct backbone model for the pentameric α-helical bundle of ETM. The disruptive effects caused by terminal lysines probably highlight the conformational flexibility required during ion channel function.


title: Organoid culture systems to study host–pathogen interactions

text: Recent advances in host–microbe interaction studies in organoid cultures have shown great promise and have laid the foundation for much more refined future studies using these systems. Modeling of Zika virus (ZIKV) infection in cerebral organoids have helped us understand its association with microcephaly. Similarly, the pathogenesis of bacterial (Helicobacter pylori, Clostridium difficile) and viral (Norovirus, Rotaviruses) infections have been precisely dissected in organoid cultures. Additionally, direct associations between microbial colonization of tissues and diseases like cancer have also been deciphered. Here we discuss the most recent and striking studies on host–microbe interactions in organoid cultures, highlighting various methods which can be used for developing microbe-organoid co-culture systems.


title: Fluorogenic RT–PCR assay (TaqMan) for detection and classification of bovine viral diarrhea virus

text: Abstract A single tube fluorogenic RT–PCR-based ‘TaqMan’ assay was developed for detection and classification of bovine viral diarrhea virus (BVDV). TaqMan–PCR was optimized to quantify BVD virus using the ABI PRISM 7700 sequence detection system and dual-labeled fluorogenic probes. Two different gene specific labeled fluorogenic probes for the 5′ untranslated region (5′ UTR) were used to differentiate between BVD types I and II. Sensitivity of the single tube TaqMan assay was compared with two-tube TaqMan assay and standard RT–PCR using 10-fold dilutions of RNA. Single tube TaqMan assay was 10–100-fold more sensitive than the two-tube TaqMan assay and the standardized single tube RT–PCR. Specificity of the assay was evaluated by testing different BVD virus strains and other bovine viruses. A total of 106 BVD positive and negative pooled or single serum samples, field isolates and reference strains were tested. Quantitation of cRNA from types I and II BVD virus was accomplished by a standard curve plotting cycle threshold values (C T) versus copy number. Single tube TaqMan–PCR assay was sensitive, specific and rapid for detection, quantitation and classification of BVD virus.


title: Current literature in mass spectrometry

text: In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books, Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (6 Weeks journals ‐ Search completed at 4th. Oct. 2006)


title: The prophylactic effect of different levels of positive endexpiratory pressure on the incidence rate of atelectasis after cardiac surgery: A Randomized Controlled Trial

text: Background: The use of positive end-expiratory pressure (PEEP) can have an important role as one of the ways to prevent and treat atelectasis, but it seems that there is still no consensus about its beneficial level. The aim of this study was to determine the effect of different levels of PEEP on the incidence of atelectasis after heart surgery. Methods: This is a double-blind randomized controlled trial that was adopted from a research project recorded in the Iranian Registry of Clinical Trials. This paper is the result of a research project undertaken at Fatemeh Zahra Hospital (Mazandaran Heart Center) in 2015. 180 patients underwent open heart surgery were selected and were divided randomly into three groups: control, PEEP=8, and PEEP=10 (60 in each group). The patients in the two PEEP8 and PEEP10 intervention groups separately received 8 cm H2O and 10 cm H2O PEEP, respectively, 30 minutes after admission to the ICU for 4 hours and then received 5 cm H2O PEEP until extubation. Atelectasis was examined two hours after the extubation and on the third day after surgery. Results: The incidence rates of atelectasis two hours after extubation on the first day of surgery were 22 (36.7%), 20 (33.3%) and 10 (16.7%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were statistically significant among the three groups (p=0.035). The incidence rates of atelectasis on the third day after surgery were 39 (65%), 36 (60%) and 21 (35%) patients in the control, PEEP8 and PEEP10 groups, respectively. The differences were also statistically significant among the three groups (p=0.003). Conclusion: The use of 10 cm H2O PEEP can lead to a reduction in the incidence of atelectasis, intubation time at the ICU and length of ICU and hospital stay. Given that this level of PEEP is effective, this method is recommended to be used in postoperative care of patients.


title: Hindsight: A re-analysis of the severe acute respiratory syndrome outbreak in Beijing

text: Summary Objective To review the severe acute respiratory syndrome (SARS) epidemic in Beijing using basic epidemiological principles omitted from the original analysis. Study design Analysis of Prospective surveillance data for Beijing collected during the outbreak. Methods Surveillance data were reclassified according to World Health Organization criteria. Cases previously excluded without date of onset of illness were included in the epidemic curve from estimates using the average time between date of onset and date of hospitalization for cases with both dates. Cases who failed to give a contact history were now included; 7% ( n = 5 ) of cases during the import phase and 61% ( n = 365 ) during the peak phase. Previously excluded cases were included for plotting on an epidemic curve, and basic spot mapping for distribution of cases was used from attack rates recalculated for age, gender, occupation, residential location, date of onset of illness and demographics. Results The spot map effectively illustrated clusters by residency, with the inner-city sustaining the highest attack rate (33.42 per 100,000), followed by an easterly distribution 5–30km away (21.62 per 10,000), and lowest in districts 60–160km away (9.21 per 100,000). The new epidemic curve shows the outbreak commencing 10 days earlier than initially reported, with a three-fold greater increase in cases during the escalation phase than previously estimated. Conclusion In hindsight, the investigation of the Beijing SARS would have benefited from the use of spot maping as an essential outbreak tool for early identification of specific geographical area(s) for quarantining. If a spot map of incidence density rates was used during the early phase of the outbreak, the inner city might have been identified as a major risk factor requiring rapid quarantining. Contact history became uncommon as the outbreak progressed, suggesting that hospitals were over-burdened or pathogenesis and environment risk factors changed, strengthening the usefulness of early spot mapping and the need to modify risk factors included as contact history as the epidemic progresses.


title: Molecular epidemiology and phylogenetic analysis of diverse bovine astroviruses associated with diarrhea in cattle and water buffalo calves in China

text: Astroviruses are the principal causative agents of gastroenteritis in humans and have been associated with diarrhea in other mammals as well as birds. However, astroviral infection of animals had been poorly studied. In the present study, 211 rectal swabs collected from cattle and water buffalo calves with mild to severe diarrhea were tested for bovine astrovirus (BAstV) by RT-PCR. Results: 92/211 (43.6%) samples were positive for BAstV, at a rate of 46.10% (71/154) in cattle and 36.84% (21/57) in water buffalo. Phylogenetic analysis based on the partial and full-length of 25 ORF2 amino acid sequences obtained in this study classified the Guangxi BAstVs isolates into five subgroups under the genus of Mamastrovirus, genotype MAstV33, which suggested that the water buffalo was a new host of this genogroup that previously included only cattle and roe deer. Despite the origin of the host, the Guangxi BAstV isolates were closely related to the BAstV Hong Kong isolates (B18/HK and B76-2/HK), but highly divergent from the BAstV NeuroS1 isolate previously associated with neurologic disease in cattle in the U.S.A. Nucleotide sequence-based characterization of the ORF1b/ORF2 junction and corresponding overlapping regions showed distinctive properties, which may be common to BAstVs. Our results suggested that cattle and water buffalo are prone to infection of closely related astroviruses, which probably evolved from the same ancestor. The current study described astroviruses in water buffalo for the first time and is thus far among the largest epidemiological investigations of BAstV infection in cattle conducted in China.


docid: mgegswvn

title: Enzyme-linked immunosorbent assay for the detection of the coronavirus-like agent and its antibodies in pigs with porcine epidemic diarrhea

text: Abstract An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of the coronavirus-like agent in feces of pigs naturally affected with porcine epidemic diarrhea (PED) or experimentally infected with the CV777 isolate. The assay was specific and more sensitive than electron microscopy. An ELISA blocking assay is described for the detection and titration of antibodies. Specific antibody formation was demonstrated in pigs experimentally infected with CV777 and in swine naturally affected with PED.


title: Histophilosis as a Natural Disease

text: Histophilus somni is responsible for sporadic disease worldwide in cattle and, to a lesser extent, in small ruminants, bighorn sheep (Ovis canadensis), and North American bison (Bison bison). The importance of H. somni diseases can be attributed to improved clinical and laboratory recognition, combined with the growth in intensive management practices for cattle. Although outbreaks of bovine histophilosis can occur year-round, in northern and southern hemispheres, it is most frequent in late fall and early winter. Weather, stress, dietary changes, and comingling of cattle are likely to be major triggers for outbreaks. The most frequent clinical expressions of histophilosis include undifferentiated fever, fibrinosuppurative pneumonia, encephalitis-leptomeningitis, necrotizing myocarditis, and diffuse pleuritis. Neurological disease occurs either as thrombotic meningoencephalitis (TME) or as suppurative meningitis with ventriculitis. Acute myocarditis is characteristically necrotizing and generally involves one or both papillary muscles in the left ventricular myocardium. Biofilm-like aggregates of bacteria occur in capillaries and veins in myocardium, in the central nervous system, and on endocardial surfaces. H. somni is a component of bovine respiratory disease (BRD) complex. In our experience, it is most commonly diagnosed in subacute-to-chronic polymicrobial pulmonary infections in combination with Mannheimia haemolytica, Trueperella pyogenes, Pasteurella multocida, or Mycoplasma bovis. Other, less common forms of H. somni disease present as polyarthritis/tenosynovitis, abortion with placentitis and fetal septicemia, epididymitis-orchitis, and ocular infections. It is likely that H. somni is under-recognized clinically and diagnostically. Most state and provincial laboratories in North America rely on bacterial isolation to confirm infection. The use of more sensitive detection methods on field cases of histophilosis will help resolve the pathogenesis of H. somni in natural outbreaks, and whether the disease is as common elsewhere as it is in Canada.


title: Triterpenoids from the stems of Tripterygium regelii

text: Abstract Three new triterpenoids, triregelolides A, B (1, 2), and triregeloic acid (3), were isolated from the stems of Tripterygium regelii along with twenty known triterpene analogues (4–23). The structures of three new compounds were identified by analyzing their NMR spectroscopic and HRESIMS data. Compounds 4, 7, 8, 10, 13, 14, 17, 21–23 were isolated from T. regelii for the first time. Compounds 3, 5, 6, 8, 9, 10, 14 and 16 showed inhibitory effects on the proliferation of human breast cancer cells MCF-7 by 24.1%, 69.6%, 72.8%, 21.6%, 23.1%, 43.3%, 25.5% and 23.5% (p <0.05) at a concentration of 10μM, respectively.


title: Sore throat in COVID‐19: Comment on “Clinical characteristics of hospitalized patients with SARS‐CoV‐2 infection: A single arm meta‐analysis”

text: We read with interest the recent meta-analysis by Sun et al.1 that included 50466 patients with Coronavirus Disease 2019 (COVID-19). The author found that fever and cough were the most common symptoms, and several subjects had muscle soreness or fatigue. In addition, they reported that "by reading the included literature, we found that diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare".1 This article is protected by copyright. All rights reserved.


docid: mpmneelo

title: The New Public Health Hegemony: Response to Severe Acute Respiratory Syndrome (SARS) in Toronto

text: The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak presented a challenging period for public health in Toronto. Many old and new public health measures were implemented at local, national and global levels, in an attempt to control the outbreak of the disease. Among these, surveillance mechanisms dominated, which involved new epidemiological techniques and statistical profiling strategies. In this paper, Gramsci's concept of hegemony is used to further understandings of public health governance during the outbreak of emerging infectious diseases. Specifically, the function of the discourse of ‘risk’ in public health governance is examined, along with public health as a ‘moral agent’ in the naturalization of specific public health measures. In addition, the pervasive discourse of ‘security’ is discussed in relation to current public health practices. These characteristics of public health are examined with consideration of their potential for propagating social exclusion and stigmatization of individuals and communities. The specific case of SARS in Toronto is used to examine the implications of public health as a mechanism for social control and reproduction rather than the promotion of equality in health throughout the population.


title: Forecasting the incidence of tuberculosis in China using the seasonal auto-regressive integrated moving average (SARIMA) model

text: Abstract Objectives The aims of this study were to develop a forecasting model for the incidence of tuberculosis (TB) and analyze the seasonality of infections in China; and to provide a useful tool for formulating intervention programs and allocating medical resources. Methods Data for the monthly incidence of TB from January 2004 to December 2015 were obtained from the National Scientific Data Sharing Platform for Population and Health (China). The Box–Jenkins method was applied to fit a seasonal auto-regressive integrated moving average (SARIMA) model to forecast the incidence of TB over the subsequent six months. Results During the study period of 144 months, 12,321,559 TB cases were reported in China, with an average monthly incidence of 6.4426 per 100,000 of the population. The monthly incidence of TB showed a clear 12-month cycle, and a seasonality with two peaks occurring in January and March and a trough in December. The best-fit model was SARIMA (1,0,0)(0,1,1)12, which demonstrated adequate information extraction (white noise test, p> 0.05). Based on the analysis, the incidence of TB from January to June 2016 were 6.6335, 4.7208, 5.8193, 5.5474, 5.2202 and 4.9156 per 100,000 of the population, respectively. Conclusions According to the seasonal pattern of TB incidence in China, the SARIMA model was proposed as a useful tool for monitoring epidemics.