title: Strategy implementation research in hospitality and tourism: Current status and future potential

text: Abstract To achieve their business objectives, hospitality and tourism organizations need effective implementation as well as consistent strategy formulation. However, the implementation aspect of strategy has attracted relatively less scholarly interest than strategic planning despite its critical role in achieving performance outcomes. Consequently, it is timely to provide an in-depth analysis of the strategy implementation literature. This is particularly the case in hospitality and tourism management where comprehensive literature reviews of strategy implementation have been lacking. To address the knowledge gap, the authors conduct a systematic literature review of 139 articles that appeared in 42 journals over the period 1988-2019. The items were grouped into six topic clusters with a view to generating novel research questions that have the potential to advance the field. We identify four main gaps that should be addressed and suggest prospective research directions.


title: Epidemiology and prevention of pediatric viral respiratory infections in health-care institutions.

text: Nosocomial viral respiratory infections cause considerable illness and death on pediatric wards. Common causes of these infections include respiratory syncytial virus and influenza. Although primarily a community pathogen, rhinovirus also occasionally results in hospitalization and serious sequelae. This article reviews effective infection control interventions for these three pathogens, as well as ongoing controversies.


title: Herintreders gebaat bij duidelijkheid en ruimte

text: Tienduizenden herintreders schieten te hulp vanwege covid-19. Hoe werk je effectief en in een positieve sfeer met hen samen?


Low prevalence of bronchial asthma and chronic obstructive lung disease among intensive care unit patients with COVID‐19


INFOGRAPHIC Title: Recommendations for perioperative Coronavirus (COVID-19) testing


title: The use of animals as a surveillance tool for monitoring environmental health hazards, human health hazards and bioterrorism

text: Abstract This review discusses the utilization of wild or domestic animals as surveillance tools for monitoring naturally occurring environmental and human health hazards. Besides providing early warning to natural hazards, animals can also provide early warning to societal hazards like bioterrorism. Animals are ideal surveillance tools to humans because they share the same environment as humans and spend more time outdoors than humans, increasing their exposure risk. Furthermore, the biologically compressed lifespans of some animals may allow them to develop clinical signs more rapidly after exposure to specific pathogens. Animals are an excellent channel for monitoring novel and known pathogens with outbreak potential given that more than 60 % of emerging infectious diseases in humans originate as zoonoses. This review attempts to highlight animal illnesses, deaths, biomarkers or sentinel events, to remind human and veterinary public health programs that animal health can be used to discover, monitor or predict environmental health hazards, human health hazards, or bioterrorism. Lastly, we hope that this review will encourage the implementation of animals as a surveillance tool by clinicians, veterinarians, ecosystem health professionals, researchers and governments.


title: Analysis of the Healthcare MERS-CoV Outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June–August 2015 Using a SEIR Ward Transmission Model

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging zoonotic coronavirus that has a tendency to cause significant healthcare outbreaks among patients with serious comorbidities. We analyzed hospital data from the MERS-CoV outbreak in King Abdulaziz Medical Center, Riyadh, Saudi Arabia, June–August 2015 using the susceptible-exposed-infectious-recovered (SEIR) ward transmission model. The SEIR compartmental model considers several areas within the hospital where transmission occurred. We use a system of ordinary differential equations that incorporates the following units: emergency department (ED), out-patient clinic, intensive care unit, and hospital wards, where each area has its own carrying capacity and distinguishes the transmission by three individuals in the hospital: patients, health care workers (HCW), or mobile health care workers. The emergency department, as parameterized has a large influence over the epidemic size for both patients and health care workers. Trend of the basic reproduction number (R(0)), which reached a maximum of 1.39 at the peak of the epidemic and declined to 0.92 towards the end, shows that until added hospital controls are introduced, the outbreak would continue with sustained transmission between wards. Transmission rates where highest in the ED, and mobile HCWs were responsible for large part of the outbreak.


Pediatric Influenza and “Universal Respiratory Etiquette”: Preparing and Protecting Your Staff and the Public


title: Comparison of the performance of 2 commercial multiplex PCR platforms for detection of respiratory viruses in upper and lower tract respiratory specimens

text: Abstract The performance of the CLART® PneumoVir system with that of the Luminex xTAG RVP Fast v1 assay for detection of most common respiratory viruses in upper and lower tract respiratory specimens (n=183) from unique patients with influenza-like syndrome or lower tract respiratory infection. Nested PCR coupled to automated sequencing was used for resolution of discrepancies. Fully concordant results were obtained for a total of 122 specimens, whereas 56 specimens gave partially (n=21) or fully discordant (n=35) results (Kappa coefficient, 0.62). The overall specificity of the Luminex xTAG RVP Fast v1 assay was slightly higher than that of the CLART® PneumoVir assay for human bocavirus, influenza A virus/H3N2, influenza B virus, human metapneumovirus, and parainfluenza virus, whereas the sensitivity of the latter was higher for most targeted viruses except, notably, for picornaviruses. This was irrespective of either the origin of the respiratory specimen or the age group to which the patients belonged.


title: Implementation and Workflow of a Telehealth Clinic in Neurosurgery During the COVID-19 Pandemic

text: • Telehealth is a viable option for ambulatory care. • Numerous benefits of telehealth implementation. • Workflow provided for telehealth clinic.


title: Electrochemical Sensors for Clinic Analysis

text: Demanded by modern medical diagnosis, advances in microfabrication technology have led to the development of fast, sensitive and selective electrochemical sensors for clinic analysis. This review addresses the principles behind electrochemical sensor design and fabrication, and introduces recent progress in the application of electrochemical sensors to analysis of clinical chemicals such as blood gases, electrolytes, metabolites, DNA and antibodies, including basic and applied research. Miniaturized commercial electrochemical biosensors will form the basis of inexpensive and easy to use devices for acquiring chemical information to bring sophisticated analytical capabilities to the non-specialist and general public alike in the future.


title: An evaluation of the global network of field epidemiology and laboratory training programmes: a resource for improving public health capacity and increasing the number of public health professionals worldwide

text: BACKGROUND: Given that many infectious diseases spread rapidly, across borders and species, there is a growing worldwide need to increase the number of public health professionals skilled in controlling infectious epidemics. Needed also are more public health professionals skilled in non-communicable disease surveillance and interventions. As a result, we surveyed all 57 field epidemiology training programmes (FETPs) that are members of the Training Program in Epidemiology and Public Health Interventions Network (TEPHINET), to evaluate the progress of the FETPs, the only global applied epidemiology network, toward increasing public health capacity globally. METHODS: Data on the FETP programmes and the training they provide were abstracted from TEPHINET membership surveys and verified with FETP directors for all FETPs that were members of TEPHINET in 2012. Data on abstracts submitted to the recent TEPHINET Global Scientific Conference, on recent accomplishments by each FETP, and on quality improvement were also compiled to provide a worldwide view of the public health human resource capacity produced by these programmes. RESULTS: A total of 6980 public health professionals worldwide have graduated from an FETP or from the Center for Disease Control and Prevention’s Epidemiology Intelligence Service (EIS). FETP residents and graduates participate in key public health prevention, control, and response activities. Each FETP has adapted its curriculum and objectives over time to align with its country’s public health priorities. FETPs are well integrated into their national public health infrastructures, and they have many partners at the national, regional and global levels. CONCLUSION: FETPs are a competent and diverse source of highly skilled public health professionals who contribute significantly to public health’s global human resource needs. This finding is evidenced by 1) the training curricula that were adapted over time to meet public health’s human resource needs, 2) the FETPs’ continued support from internal and external partners, 3) the increasing number of FETP residents and graduates and their increasing contribution to effective public health work, and 4) the increased quality improvement initiatives facilitated through the FETPs membership in one global network, TEPHINET.


title: Hydrophobic Derivatives of Glycopeptide Antibiotics as Inhibitors of Protein Kinases

text: As key regulators of cell signaling, protein kinases (PKs) are attractive targets for therapeutic intervention in a variety of diseases. Herein, we report for the first time the inhibitory activity of polycyclic peptides, particularly, derivatives of glycopeptide antibiotics teicoplanin and eremomycin, against a panel of 12 recombinant human protein kinases and two protein kinases (CK1 and CK2) isolated from rat liver. Several of the investigated compounds inhibited various PKs with IC(50) values below 10 μM and caused >90% suppression of the enzyme activity at 10 μM concentration. Kinetic analysis of the protein kinase CK2α inhibition by the teicoplanin aglycon analogue (7) demonstrated the non-competitive mechanism of inhibition (with regard to ATP). Interestingly, the inhibitory activity of some investigated compounds correlated with the earlier described antiviral activity against HIV, HCV, and other corona- and flaviviruses.


title: Prevalence of rotavirus (GARV) and coronavirus (BCoV) associated with neonatal diarrhea in calves in western Algeria

text: OBJECTIVE: To study the prevalence of bovine group A rotavirus (GARV) and bovine coronavirus (BCoV) in diarrheic feces from calves and the sensitive's parameters such as age group and sex. METHODS: Feces samples from 82 diarrheic dairy calves from farms around Tiaret (Western Algeria) were collected. These samples were tested by ELISA assay. RESULTS: The results showed that the prevalence of rotavirus and coronavirus infection are 14.63% (12.2% alone and 2.43% associated with bovine coronavirus) and 20.73% (18.3% alone and 2.43% associated with GARV), respectively. CONCLUSIONS: The present study demonstrates that the both BCoV and GARV are involved in the neonatal calves' diarrhea, where the frequency of BCoV is clearly higher than that of GARV.


title: The Network of Angiotensin Receptors in Breast Cancer

text: The renin-angiotensin system (RAS) is a network of proteins regulating many aspects of human physiology, including cardiovascular, pulmonary, and immune system physiology. The RAS is a complicated network of G-protein coupled receptors (GPCRs) (i.e., AT1R, AT2R, MASR, and MRGD) orchestrating the effects of several hormones (i.e., angiotensin II, angiotensin (1–7), and alamandine) produced by protease-based transmembrane receptors (ACE1 and ACE2). Two signaling axes have been identified in the RAS endocrine system that mediate the proliferative actions of angiotensin II (i.e., the AT1R-based pathway) or the anti-proliferative effects of RAS hormones (i.e., the AT2R-, MAS-, and MRGD-based pathways). Disruption of the balance between these two axes can cause different diseases (e.g., cardiovascular pathologies and the severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-based COVID-19 disease). It is now accepted that all the components of the RAS endocrine system are expressed in cancer, including cancer of the breast. Breast cancer (BC) is a multifactorial pathology for which there is a continuous need to identify novel drugs. Here, I reviewed the possible roles of both axes of the RAS endocrine network as potential druggable pathways in BC. Remarkably, the analysis of the current knowledge of the different GPCRs of the RAS molecular system not only confirms that AT1R could be considered a drug target and that its inhibition by losartan and candesartan could be useful in the treatment of BC, but also identifies Mas-related GPCR member D (MRGD) as a druggable protein. Overall, the RAS of GPCRs offers multifaceted opportunities for the development of additional compounds for the treatment of BC.


title: Potential Risk of Virus Carryover by Fabrics of Personal Protective Gowns

text: Personal protective gowns and coveralls are classified based on barrier efficiency that validates protection from fluid penetration under certain pressures. Materials standardized in this system have been found suitable for emergency medical practices confronting highly contagious diseases. Nevertheless, adhesion of blood, and body fluids from virus-infected patients to the surface of protective clothing still imposes a risk of pathogen transmission in the process of doffing, or undressing. We performed a small-scale experiment to test the possibility of infectious virus carryover on the surface of different fabrics used in commercially available protective gowns. Application of a lentivirus vector that expresses green fluorescent protein allowed easy monitoring of infectious viral loads on fabrics. Results indicate that fabrics of level-3 surgical gowns serve better to reduce virus transmission compared to fabrics of chemical protective clothing with the same or higher barrier efficiency. Analysis of sliding angles provided indexes of fluid repellency, which were inversely related to virus carryover potentials. Droplets of infectious body fluids may easily roll off fabrics with water-repellent finishing. Thus, virus carryover is a measurable risk factor to be considered for better choice of personal protective clothing.


title: Exploring the Nontechnical Competencies for On-scene Public Health Responders in Chemical, Biological, Radiological and Nuclear Emergencies: A Qualitative Study

text: Abstracts Objectives The purpose of this study was to define and delineate specific nontechnical competencies for first-line public health responders in Chemical, Biological, Radiological and Nuclear (CBRN) emergencies in China. Study design A qualitative study was conducted in China involving interviews with key informants in the field of health response to CBRN disasters. Methods One-on-one in-depth interviews were carried out with 20 participants, including expert members of National Medical Response Teams for CBRN Disasters, officials at emergency management authorities, and scholars of academic institutions related to CBRN emergency. Interviews were recorded with audio equipment, transcribed and coded into codable passages according to grounded theory with NVivo software. Themes were identified within the transcriptions by using thematic analysis. Results 159 codable passages were produced. Eight domains of nontechnical core competencies were identified: (1) situation awareness, (2) communication skills, (3) collaboration, (4) resource management, (5) task management, (6) cultural competency, (7) austere environment skills, and (8) physical stamina. Conclusions The study identified a variety of competencies for on-scene public health responders in CBRN emergencies. The findings of this study could specifically benefit development of strategy and improvement of content of education and training. Further research that involves input from the disaster response community at large are needed for the validation of these competencies.


Can I Get Force Majeure from a Novel Coronavirus?


Universal testing for COVID-19 in pregnant women admitted for delivery: prevalence of peripartum infection and rate of asymptomatic carriers at four New York hospitals within an integrated healthcare system


title: Amino acids 1 to 422 of the spike protein of SARS associated coronavirus are required for induction of cyclooxygenase-2

text: The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV). To evaluate the molecular mechanisms involved in the viral infection, in this study, we investigated the role of SARS-CoV Spike (S) protein in the regulation of cyclooxygenase-2 (COX-2). Expression of COX-2 stimulated by the S protein was verified by RT-PCR and western blot assay. To explore the relationship between S and COX-2, we constructed a series of plasmids containing truncated N-terminal fragments of the SARS-CoV S gene (designated from Sa to Si), which encoded truncated S proteins, and investigated whether these truncated proteins could induce effective expression of COX-2 in 293T cells. Our results showed that S(d) that encoded a truncated S protein with 422 amino acid residues (from 1 to 422 aa), a part of 672 amino-acid S1 subunit is crucial for the induction of COX-2 expression. Immunofluorescence examinations also give the evidence that these N terminal 422 amino acids of the S protein were also required for the correct localization of the protein. We also compared S protein sequences of SARS-CoV isolated during the SARS break with that from palm civets, a possible source of SARS-CoV found in humans. S protein residues (344, 360), which mutated in the epitome from palm civet to human being were characterized in 3D modeling of 252–375 amino acid fragment. Collectively, these results indicate that S protein of SARS-CoV induces the expression of COX-2 and an N-terminal fragment of the Spike protein is crucial for the induction. Our finding may provide clue for the induction of inflammation by SARS-CoV and cast insight into the severity of the SARS epidemic.


title: Viral etiology of acute lower respiratory tract infections in hospitalized young children in Northern Taiwan

text: Background Lower respiratory tract infections (LRTIs) comprise a great proportion of diagnoses among hospitalized children. This study identifies the viral pathogens causing LRTIs in young children and compares their clinical features and disease severity. Methods Children younger than 36 months old, hospitalized at a medical center in Northern Taiwan with acute bronchiolitis or pneumonia from April to December 2007, were prospectively enrolled. Nasopharyngeal aspiration fluid samples were sent for virus culture, for direct immunofluorescence test of respiratory syncytial virus (RSV), for rapid influenza viral identification, and for polymerase chain reaction of human metapneumovirus (hMPV), human boca virus (hBoV), and human corona virus. The clinical features and laboratory findings were recorded and analyzed. Results A total of 48 children were enrolled. RSV was the most common pathogen (41.7%), followed by hMPV (27.1%), hBoV, and enterovirus (both 6.3%). There were no significant differences in clinical presentation and disease severity between the RSV and hMPV groups. However, the hMPV group had a higher mixed infection rate (p = 0.038). Fourteen children had no identifiable viruses. Children with single, dual, and triple pathogens numbered 26, 7, and 1, respectively. The mixed infection rate reached 23.5% among 34 children with identifiable viruses. Children with a higher severity score had greater chance to develop asthma in the next 2 years (p = 0.042). Conclusion RSV is the most common pathogen causing LRTIs in young children, followed by hMPV. The hMPV group had higher mixed infection rate than RSV group. hBoV does circulate in northern Taiwan.


title: Rhinoviruses, Allergic Inflammation, and Asthma

text: Viral infections affect wheezing and asthma in children and adults of all ages. In infancy, wheezing illnesses are usually viral in origin, and children with more severe wheezing episodes are more likely to develop recurrent episodes of asthma and to develop asthma later in childhood. Children who develop allergen-specific immunoglobulin E (allergic sensitization), and those who wheeze with rhinoviruses (HRV) are at especially high risk for asthma. In older children and adults, HRV infections generally cause relatively mild respiratory illnesses and yet contribute to acute and potentially severe exacerbations in patients with asthma. These findings underline the importance of understanding the synergistic nature of allergic sensitization and infections with HRV in infants relative to the onset of asthma and in children and adults with respect to exacerbations of asthma. This review discusses clinical and experimental evidence of virus/allergen interactions and evaluates theories which relate immunologic responses to respiratory viruses and allergens to the pathogenesis and disease activity of asthma. Greater understanding of the relationship between viral respiratory infections, allergic inflammation, and asthma is likely to suggest new strategies for the prevention and treatment of asthma.


title: Breakdown of the Blood–Retinal Barrier

text: Macular edema that results from blood–retinal barrier (BRB) breakdown is a cause of significant visual loss associated with a variety of ocular disorders. BRB breakdown is a complex process that is regulated by multiple factors and involves different mechanisms. A variety of therapeutic approaches have shown modest suppression of macular edema, but to obtain greater efficacy, it is likely that multiple molecules, operating through distinct mechanisms, may need to be targeted. Studies aimed at identifying key target molecules and the optimal strategies for inhibiting them are ongoing in several laboratories.


title: When will the battle against novel coronavirus end in Wuhan: A SEIR modeling analysis

text: BACKGROUND: Recent outbreak of 2019-nCoV in Wuhan raised serious public health concerns. By February 15, 2020 in Wuhan, the total number of confirmed infection cases has reached 37 914, and the number of deaths has reached 1123, accounting for 56.9% of the total confirmed cases and 73.7% of the total deaths in China. People are eager to know when the epidemic will be completely controlled and when people's work and life will be on the right track. METHOD: In this study we analyzed the epidemic dynamics and trend of 2019-nCoV in Wuhan by using the data after the closure of Wuhan city till February 12, 2020 based on the SEIR modeling method. RESULTS: The optimal parameters were estimated as R(0) = 1.44 (interquartile range: 1.40-1.47), TI = 14 (interquartile range = 14-14) and TE = 3.0 (interquartile range = 2.8-3.1). Based on these parameters, the number of infected individuals in Wuhan city may reach the peak around February 19 at about 47 000 people. Once entering March, the epidemic would gradually decline, and end around the late March. It is worth noting that the above prediction is based on the assumption that the number of susceptible population N = 200 000 will not increase. If the epidemic situation is not properly controlled, the peak of infected number can be further increased and the peak time will be a little postponed. It was expected that the epidemic would subside in early March, and disappear gradually towards the late March. CONCLUSIONS: The epidemic situation of 2019-nCoV in Wuhan was effectively controlled after the closure of the city, and the disease transmission index also decreased significantly. It is expected that the peak of epidemic situation would be reached in late February and end in March.


title: Metagenomics for neurological infections — expanding our imagination

text: Over the past two decades, the diagnosis rate for patients with encephalitis has remained poor despite advances in pathogen-specific testing such as PCR and antigen assays. Metagenomic next-generation sequencing (mNGS) of RNA and DNA extracted from cerebrospinal fluid and brain tissue now offers another strategy for diagnosing neurological infections. Given that mNGS simultaneously assays for a wide range of infectious agents in an unbiased manner, it can identify pathogens that were not part of a neurologist’s initial differential diagnosis either because of the rarity of the infection, because the microorganism has not been previously associated with a clinical phenotype or because it is a newly discovered organism. This Review discusses the technical advantages and pitfalls of cerebrospinal fluid mNGS in the context of patients with neuroinflammatory syndromes, including encephalitis, meningitis and myelitis. We also speculate on how mNGS testing potentially fits into current diagnostic testing algorithms given data on mNGS test performance, cost and turnaround time. Finally, the Review highlights future directions for mNGS technology and other hypothesis-free testing methodologies that are in development.


title: Addressing Injecting Drug Use in Asia and Eastern Europe

text: While the global HIV incidence dropped about 20 % in the past 10 years, HIV incidences among people who inject drugs (PWID) in Asia and Europe continue to increase and to account for high proportions of new HIV infections among PWID globally. Great changes have been observed in this region, such as progressing from rejection to acceptance of harm reduction strategies in Asian countries, but no such change has occurred in Eastern European countries. China has quickly scaled up harm reduction activities nationwide, resulting in the decline of HIV incidence and HIV prevalence among PWID since 2006. However, insufficient scaling up of harm reduction programs in other countries has failed to slow down their HIV epidemics. In Eastern European countries where the spread of HIV among PWID is the most severe, only about 15 % of funding for harm reduction programs are from domestic sources. Strong political and financial commitment from countries in this region is urgently needed to quickly scale up evidence-based harm reduction strategies in order to prevent the HIV epidemic from spreading rapidly from PWID to the heterosexual general population.


title: Protective immunity by an engineered DNA vaccine for Mayaro virus

text: Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge.


title: Practical synthesis of peptide C-terminal aldehyde on a solid support

text: We have investigated practical synthetic routes for the preparation of peptide aldehyde on a solid support. Peptide aldehyde was synthesized via efficient transformation of acetal/thioacetal structures.


title: The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions

text: The novel corona virus disease has shaken the entire world with its deadly effects and rapid transmission rates, posing a significant challenge to the healthcare authorities to develop suitable therapeutic solution to save lives on earth. The review aims to grab the attention of the researchers all over the globe, towards the role of ACE2 in COVID-19 disease. ACE2 serves as a molecular target for the SARS-CoV-2, to enter the target cell, by interacting with the viral glycoprotein spikes. However, the complexity began when numerous studies identified the protective response of ACE2 in abbreviating the harmful effects of vasoconstrictor, anti-inflammatory peptide, angiotensin 2, by mediating its conversion to angiotensin-(1–7), which exercised antagonistic actions to angiotensin 2. Furthermore, certain investigations revealed greater resistance among children as compared to the geriatrics, towards COVID-19 infection, despite the elevated expression of ACE2 in pediatric population. Based upon such evidences, the review demonstrated possible therapeutic interventions, targeting both the protective and deleterious effects of ACE2 in COVID-19 disease, primarily inhibiting ACE2-virus interactions or administering soluble ACE2. Thus, the authors aim to provide an opportunity for the researchers to consider RAAS system to be a significant element in development of suitable treatment regime for COVID-19 pandemic.


title: Investigation into the causes of canine infectious respiratory disease: antibody responses to canine respiratory coronavirus and canine herpesvirus in two kennelled dog populations

text: Two training centres for working dogs were monitored for one year to determine the presence of viruses and viral antibodies and their association with canine infectious respiratory disease (CIRD). Tonsillar swabs and serum were obtained from dogs on entry into the kennels and in regular intervals thereafter. Additional samples were collected during outbreaks of CIRD. The swabs were examined by virus culture and PCR for canine parainfluenza virus, canine adenovirus, canine herpesvirus (CHV) and canine respiratory coronavirus (CRCoV). Furthermore the prevalence of antibodies to CHV and CRCoV was determined. During this study CIRD was reported mainly in one of the two kennels investigated. In that kennel antibody responses to CRCoV indicated a seasonal occurrence of the virus, which coincided with two outbreaks of respiratory disease. CHV antibody responses were detected throughout the year. In the other kennel, which reported few cases of CIRD a high prevalence of antibodies to CRCoV was detected on entry but only sporadic seroconversions to CRCoV or CHV. By PCR three dogs were found positive for CRCoV in one kennel whereas all PCR tests for other viruses were negative for both kennels. Virus culture failed to detect any viruses in either kennel.


title: Toll-like receptors in immunity and inflammatory diseases: Past, present, and future

text: Abstract The immune system is a very diverse system of the host that evolved during evolution to cope with various pathogens present in the vicinity of environmental surroundings inhabited by multicellular organisms ranging from achordates to chordates (including humans). For example, cells of immune system express various pattern recognition receptors (PRRs) that detect danger via recognizing specific pathogen-associated molecular patterns (PAMPs) and mount a specific immune response. Toll-like receptors (TLRs) are one of these PRRs expressed by various immune cells. However, they were first discovered in the Drosophila melanogaster (common fruit fly) as genes/proteins important in embryonic development and dorso-ventral body patterning/polarity. Till date, 13 different types of TLRs (TLR1-TLR13) have been discovered and described in mammals since the first discovery of TLR4 in humans in late 1997. This discovery of TLR4 in humans revolutionized the field of innate immunity and thus the immunology and host-pathogen interaction. Since then TLRs are found to be expressed on various immune cells and have been targeted for therapeutic drug development for various infectious and inflammatory diseases including cancer. Even, Single nucleotide polymorphisms (SNPs) among various TLR genes have been identified among the different human population and their association with susceptibility/resistance to certain infections and other inflammatory diseases. Thus, in the present review the current and future importance of TLRs in immunity, their pattern of expression among various immune cells along with TLR based therapeutic approach is reviewed.


title: A retrospective clinical and epidemiological study on feline coronavirus (FCoV) in cats in Istanbul, Turkey

text: Abstract The presence of antibodies to feline coronavirus (FCoV) and feline immunodeficiency virus (FIV), together with feline leukemia virus (FeLV) antigen was investigated in 169 ill household and stray cats attending a veterinary surgery in Istanbul in 2009–14. The estimated FCoV and FIV seroprevalence (95% confidence intervals) were 37% (30–45%) and 11% (6–16%), respectively and FeLV prevalence was 1% (0–3%). FCoV seroprevalence increased until 2 years of age, was highest in 2014 and among household cats living with other cats and with outdoor access, and was lower in FIV seropositive compared to seronegative cats. Symptoms typically associated with wet feline infectious peritonitis (FIP) including ascites, abdominal distention or pleural effusion, coupled in many cases with non-antibiotic responsive fever, were observed in 19% (32/169) of cats, and 75% (24/32) of these cats were FCoV seropositive. FCoV seropositivity was also associated with a high white blood cell count, high plasma globulin, low plasma albumin and low blood urea nitrogen. The percentage of FCoV seropositive and seronegative cats that died in spite of supportive veterinary treatment was 33% (21/63) and 12% (13/106), respectively. These results indicate that FCoV is widespread and has a severe clinical impact in cats from Istanbul. Moreover, the incidence of FCoV infections could be rising, and in the absence of effective vaccination cat owners need to be made aware of ways to minimize the spread of this virus.


title: Glycyrrhetinic acid and its derivatives as potential alternative medicine to relieve symptoms in nonhospitalized COVID‐19 patients

text: SARS‐CoV‐2 is highly infectious, and infection by this virus results in COVID‐19, manifesting predominantly symptoms in the lower respiratory system. Detection of viral genomic materials by RT‐PCR is the gold standard for diagnosis. Suspected COVID‐19 patients who had a documented history of exposure and exhibited symptoms, but did not have positive PCR test results, were generally self‐quarantined with prescriptions aiming to help attenuate their symptoms. These prescriptions are however neither specific nor highly effective for COVID‐19 treatment. Given the rapidly growing pandemic and the overwhelmed medical system, the number of self‐quarantined patients is increasing. There is an urgent need of alternative medicine to help patients relieve symptoms during self‐quarantine, and to potentially help increase their chances of survival and recovery from the infection. We report here a case of severe COVID‐19 that never had a positive PCR test result during disease progression but was confirmed with antibody test post recovery. This patient was self‐quarantined and received diammonium glycyrrhizinate (DG), a steroid‐like molecule, in combination with vitamin C as alternative medicine. This patient went through severe COVID‐19 but eventually recovered upon the implementation of this treatment regimen, suggesting potential therapeutic effects of DG as alternative medicine to help relieve COVID‐19 symptoms.


title: Scoring function for DNA–drug docking of anticancer and antiparasitic compounds based on spectral moments of 2D lattice graphs for molecular dynamics trajectories

text: Abstract We introduce here a new class of invariants for MD trajectories based on the spectral moments πk (L) of the Markov matrix associated to lattice network-like (LN) graph representations of Molecular Dynamics (MD) trajectories. The procedure embeds the MD energy profiles on a 2D Cartesian coordinates system using simple heuristic rules. At the same time, we associate the LN with a Markov matrix that describes the probabilities of passing from one state to other in the new 2D space. We construct this type of LNs for 422 MD trajectories obtained in DNA–drug docking experiments of 57 furocoumarins. The combined use of psoralens+ultraviolet light (UVA) radiation is known as PUVA therapy. PUVA is effective in the treatment of skin diseases such as psoriasis and mycosis fungoides. PUVA is also useful to treat human platelet (PTL) concentrates in order to eliminate Leishmania spp. and Trypanosoma cruzi. Both are parasites that cause Leishmaniosis (a dangerous skin and visceral disease) and Chagas disease, respectively; and may circulate in blood products collected from infected donors. We included in this study both lineal (psoralens) and angular (angelicins) furocoumarins. In the study, we grouped the LNs on two sets; set1: DNA–drug complex MD trajectories for active compounds and set2: MD trajectories of non-active compounds or no-optimal MD trajectories of active compounds. We calculated the respective πk (L) values for all these LNs and used them as inputs to train a new classifier that discriminate set1 from set2 cases. In training series the model correctly classifies 79 out of 80 (specificity=98.75%) set1 and 226 out of 238 (Sensitivity=94.96%) set2 trajectories. In independent validation series the model correctly classifies 26 out of 26 (specificity=100%) set1 and 75 out of 78 (sensitivity=96.15%) set2 trajectories. We propose this new model as a scoring function to guide DNA-docking studies in the drug design of new coumarins for anticancer or antiparasitic PUVA therapy.


Vaccinating against COVID-19: The quest for the Grail?


title: Analysis of the Genome Sequence and Prediction of B-Cell Epitopes of the Envelope Protein of Middle East Respiratory Syndrome-Coronavirus

text: The outbreak of Middle East respiratory syndrome-coronavirus (MERS-CoV) in South Korea in April 2015 led to 186 infections and 37 deaths by the end of October 2015. MERS-CoV was isolated from the imported patient in China. The envelope (E) protein, a small structural protein of MERS-CoV, plays an important role in host recognition and infection. To identify the conserved epitopes of the E protein, sequence analysis was performed by comparing the E proteins from 42 MERS-CoV strains that triggered severe pandemics and infected humans in the past. To predict the potential B cell epitopes of E protein, three most effective online epitope prediction programs, the ABCpred, Bepipred, and Protean programs from the LaserGene software were used. All the nucleotides and amino acids sequences were obtained from the NCBI Database. One potential epitope with a suitable length (amino acids 58–82) was confirmed and predicted to be highly antigenic. This epitope had scores of >0.80 in ABCpred and level 0.35 in Bepipred programs. Due to the lack of X-ray crystal structure of the E protein in the PDB database, the simulated 3D structure of the E protein were also predicted using PHYRE 2 and Pymol programs. In conclusion, using bioinformatics methods, we analyzed the genome sequence of MERS-CoV and identified a potential B-cell epitope of the E protein, which might significantly improve our current MERS vaccine development strategies.


title: International Travelers and Infectious Disease

text: Abstract International travelers have an increased risk of exposure to illness from infectious diseases caused by bacteria, viruses, and parasites. Nurse practitioners in primary and emergency care settings should have a working knowledge of common infectious diseases found in international destinations. It is important to maintain a high degree of suspicion for infectious causes when examining patients after travel with common complaints. The need to refer patients to travel health clinics and infectious disease specialists for pretravel consultation and post-travel red flags are important considerations for practice.


title: A genome-wide association study identifies major loci affecting the immune response against infectious bronchitis virus in chicken

text: Abstract Coronaviruses are a hot research topic because they can cause severe diseases in humans and animals. Infectious bronchitis virus (IBV), belonging to gamma-coronaviruses, causes a highly infectious respiratory viral disease and can result in catastrophic economic losses to the poultry industry worldwide. Unfortunately, the genetic basis of the host immune responses against IBV is poorly understood. In the present study, the antibody levels against IBV post-immunization were measured by an enzyme-linked immunosorbent assay in the serum of 511 individuals from a commercial chicken (Gallus gallus) population. A genome-wide association study using 43,211 single nucleotide polymorphism markers was performed to identify the major loci affecting the immune response against IBV. This study detected 20 significant (P <1.16×10−6) effect single nucleotide polymorphisms for the antibody level against IBV. These single nucleotide polymorphisms were distributed on five chicken chromosomes (GGA), involving GGA1, GGA3, GGA5, GGA8, and GGA9. The genes in the 1-Mb windows surrounding each single nucleotide polymorphism with significant effect for the antibody level against IBV were associated with many biological processes or pathways related to immunity, such as the defense response and mTOR signaling pathway. A genomic region containing a cluster of 13 beta-defensin (GAL1–13) and interleukin-17F genes on GGA3 probably plays an important role in the immune response against IBV. In addition, the major loci significantly associated with the antibody level against IBV on GGA1 and GGA5 could explain about 12% and 13% of the phenotypic variation, respectively. This study suggested that the chicken genome has several important loci affecting the immune response against IBV, and increases our knowledge of how to control outbreaks of infectious bronchitis.


title: Evolving Transmission Network Dynamics of COVID-19 Cluster Infections in South Korea: a descriptive study

text: Background. Extensive contact tracing and testing in South Korea allows us to investigate the transmission dynamics of the COVID-19 into diverse local communities. Objective. Understand the critical aspects of transmission dynamics in a different age, sex, and clusters with various activities. Methods. We conducted a retrospective observational study with 3,127 confirmed cases' contact tracing data from the Center for Disease and Prevention (CDC) of South Korea. We investigated network property concerning infected persons' demographics and different infection clusters. Findings. Overall, women had higher centrality scores than men after week four, when the confirmed cases rapidly increased. Older adults have higher centrality than young/middle-aged adults after week 9. In the infection clusters, young/middle-aged adults' infection clusters (such as religious gatherings and gym facilities) have higher average path lengths and diameter than older adults' nursing home infection clusters. Interpretation. Some women had higher reproduction numbers and bridged successive transmission than men when the confirmed cases rapidly increased. Similarly, some older adults (who were not residents of nursing homes) had higher reproduction numbers and bridged successive transmission than young/middle-aged adults after the peak has passed. The young/middle-aged adults' religious gatherings and group workout have caused long successive transmissions. In contrast, the older adults' nursing homes were a small world where the transmissions within a few steps can reach out to many persons.


docid: setmifik

title: Suppression subtractive hybridization method for the identification of a new strain of murine hepatitis virus from xenografted SCID mice

text: During attempts to clone retroviral determinants associated with a mouse model of Langerhans cell histiocytosis (LCH), suppression subtractive hybridization (SSH) was used to identify unique viruses in the liver of severe combined immunodeficiency (SCID) mice transplanted with LCH tissues. A partial genomic sequence of a murine coronavirus was identified, and the whole genome (31428 bp) of the coronavirus was subsequently sequenced using PCR cloning techniques. Nucleotide sequence comparisons revealed that the genome sequence of the new virus was 91-93 % identical to those of known murine hepatitis viruses (MHVs). The predicted open reading frame from the nucleotide sequence encoded all known proteins of MHVs. Analysis at the protein level showed that the virus was closely related to the highly virulent MHV-JHM strain. The virus strain was named MHV-MI. No type D retroviruses were found. Degenerate PCR targeting of type D retrovirus and 5′-RACE targeting of other types of retroviruses confirmed the absence of any retroviral association with the LCH xenografted SCID mice.


title: Study on the motion law of aerosols produced by human respiration under the action of thermal plume of different intensities

text: Abstract Predicting influence of human thermal plume on the diffusion of respiration-produced particles is an important issue for improving indoor air quality through eliminating infectious microbes efficiently. In this study, the Large Eddy Simulation was utilized to predict the effects of thermal plume of different intensities on particle diffusion. Three postures of the human body model and three room temperatures were considered. The results show that the convective heat transfer coefficient on the surface of the human body varies greatly with different postures. The coefficient is the largest when the model is in sitting posture, leading to the greatest heat transfer rate. Meanwhile, the thermal plume generated by bending the thigh increases the size of the facial thermal plume in horizon direction. The increase of the difference between indoor temperature and skin temperature causes an increase of the convective heat transfer of the manikin, leading to stronger airflow in front of the face. The thicker and faster the human thermal plume is, the more difficult it is penetrated by aerosols produced by nasal breathing, finally resulting in most particles distributed within 0.2 m thick under the roof.


title: Psychological crisis intervention response to the COVID 19 pandemic: A Tunisian centralised Protocol

text: Abstract In order to manage the urgent psychological need for support in response to the anticipated reaction of the population to the COVID-19 pandemic, we developed a new psychological crisis intervention model by implementing a centralised psychological support system for all of Tunisia. We set up a helpline which is accessible throughout the country, including those without access to Internet. This model integrates medical students, child and adolescent psychiatrists, psychiatrists, psychologists and social services to provide psychological intervention to the general population and medical staff. It will make a sound basis for developing a more effective psychological crisis intervention response system.


title: The crystal structure of nsp10-nsp16 heterodimer from SARS-CoV-2 in complex with S-adenosylmethionine

text: SARS-CoV-2 is a member of the coronaviridae family and is the etiological agent of the respiratory Coronavirus Disease 2019. The virus has spread rapidly around the world resulting in over two million cases and nearly 150,000 deaths as of April 17, 2020. Since no treatments or vaccines are available to treat COVID-19 and SARS-CoV-2, respiratory complications derived from the infections have overwhelmed healthcare systems around the world. This virus is related to SARS-CoV-1, the virus that caused the 2002-2004 outbreak of Severe Acute Respiratory Syndrome. In January 2020, the Center for Structural Genomics of Infectious Diseases implemented a structural genomics pipeline to solve the structures of proteins essential for coronavirus replication-transcription. Here we show the first structure of the SARS-CoV-2 nsp10-nsp16 2’-O-methyltransferase complex with S-adenosylmethionine at a resolution of 1.80 Å. This heterodimer complex is essential for capping viral mRNA transcripts for efficient translation and to evade immune surveillance.


title: Establishment and maintenance of a persistent infection of L132 cells by human coronavirus strain 229E

text: A persistent infection by human coronavirus 229E (HCV/229E) was established in a human continuous cell line (L132). Following the initial infection with stock HCV/229E, several cultures were established of which two (HV1 and HV4) have been maintained by continuous passage for two years. These cultures have shed high titres of infectious virus continuously into the supernatant fluid since their initiation. The persistently infected cells were resistant to homologous super-infection but supported polio virus replication to normal titres. Preliminary tests indicated that 50–100 percent of the cells contain virus. Neither interferon nor reverse transcriptase could be detected in these cultures and the presence of defective interfering particles could not be demonstrated. VH1 and VH4 coronaviruses, isolated from these persistently infected cultures (HV) and identified by 229E antiserum neutralization, were more cytocidal than the parent virus as judged by plaque characteristics and CPE however, they were indistinguishable on the basis of density, EM morphology, and genome size. Present evidence indicates that temperature plays an important but as yet undetermined role in the establishment and maintenance of stable 229E persistently infected cell cultures.


Pet theory comes to the fore in fight against SARS


docid: eweoofdk

title: Prevalence and molecular typing of Cryptosporidium in dairy cattle in England and Wales and examination of potential on-farm transmission routes

text: Abstract An average of 70 samples were collected from 80 dairy farms in England and Wales, from cattle, co-grazed sheep, wildlife and farm wastes, to investigate prevalence, potential sources and transmission routes of Cryptosporidium. At least one positive sample was detected on 74 of the farms (92.5%) by IFAT microscopy. The prevalence in cattle was 10.2% (95% CI 9.4–11.1%), with greater prevalences detected in calf samples, especially from those under 1 month (45.1%). Young calves were also more likely to be shedding Cryptosporidium parvum and larger concentrations of oocysts, whereas older calves and adult cattle were more likely to be shedding Cryptosporidium bovis and Cryptosporidium andersoni, respectively. The C. parvum subtypes detected were predominantly from types commonly identified in UK cattle (67% were either IIaA15G2R1 or IIaA17G1R1). A novel subtype, IIaA17G1R2, was identified from one cattle sample. The prevalence in co-grazed sheep was low (4%). Birds and rodents may represent significant reservoirs of Cryptosporidium due to high prevalence, large oocyst concentrations, and the detection of a C. parvum subtype known to be present in human populations, identified in samples from these wildlife. Cryptosporidium were detected in dirty water and manure, and also from pasture samples where slurry had been spread. On 64% of the farms, identical Cryptosporidium species were detected (mainly C. parvum or C. bovis) from different cattle groups on the farms, although no direct or indirect contact between the groups were recorded, apart from sharing staff. The same Cryptosporidium species were found in cattle, farm wastes and bird samples on the same farms, but rarely, or not at all, present in sheep or rodent samples. The matching of species/subtypes was also related to the proximity of the different sample sources which may indicate a potential transmission route.


The Syrian refugees crisis brings challenges to the health authorities in Europe: hepatitis A virus is a case in point


title: Elucidating the molecular physiopathology of acute respiratory distress syndrome in severe acute respiratory syndrome patients

text: Abstract Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury. It is a response to various diseases of variable etiology, including SARS-CoV infection. To date, a comprehensive study of the genomic physiopathology of ARDS (and SARS) is lacking, primarily due to the difficulty of finding suitable materials to study the disease process at a tissue level (instead of blood, sputa or swaps). Hereby we attempt to provide such study by analyzing autopsy lung samples from patient who died of SARS and showed different degrees of severity of the pulmonary involvement. We performed real-time quantitative PCR analysis of 107 genes with functional roles in inflammation, coagulation, fibrosis and apoptosis; some key genes were confirmed at a protein expression level by immunohistochemistry and correlated to the degree of morphological severity present in the individual samples analyzed. Significant expression levels were identified for ANPEP (a receptor for CoV), as well as inhibition of the STAT1 pathway, IFNs production and CXCL10 (a T-cell recruiter). Other genes unassociated to date with ARDS/SARS include C1Qb, C5R1, CASP3, CASP9, CD14, CD68, FGF7, HLA-DRA, IGF1, IRF3, MALAT-1, MSR1, NFIL3, SLPI, USP33, CLC, GBP1 and TAC1. As a result, we proposed to therapeutically target some of these genes with compounds such as ANPEP inhibitors, SLPI and dexamethasone. Ultimately, this study may serve as a model for future, tissue-based analyses of fibroinflammatory conditions affecting the lung.


title: The impact of respiratory protective equipment on difficult airway management: a randomised, crossover, simulation study

text: The current international COVID‐19 health crisis underlines the importance of adequate and suitable personal protective equipment for clinical staff during acute airway management. This study compares the impacts of standard air‐purifying respirators and powered air‐purifying respirators during simulated difficult airway scenarios. Twenty‐five anaesthetists carried out four different standardised difficult intubation drills, either unprotected (control), or wearing a standard or a powered respirator. Treatment times and wearer comfort were determined and compared. In the wearer comfort evaluation form, operators rated mobility, noise, heat, vision and speech intelligibility. All anaesthetists accomplished the treatment objectives of all study arms without adverse events. Total mean (SD) intubation times for the four interventions did not show significant differences between the powered and the standard respirator groups, being 16.4 (8.6) vs. 19.2 (5.2) seconds with the Airtraq™; 11.4 (3.4) vs. 10.0 (2.1) seconds with the videolaryngoscope; 39.2 (4.5) vs. 40.1 (4.8) seconds with the fibreoptic bronchoscope scope; and 15.4 (5.7) vs. 15.1 (5.0) seconds for standard tracheal intubation by direct laryngoscopy, respectively. Videolaryngoscopy allowed the shortest intubation times regardless of the respiratory protective device used. Anaesthetists rated heat and vision significantly higher in the powered respirator group; however, noise levels were perceived to be significantly lower than in the standard respirator group. We conclude that standard and powered respirators do not significantly prolong simulated advanced intubation procedures.


title: Alzheimer's Disease: APP, Gamma Secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, and MS4A2, and Their Relationships with Herpes Simplex, C. Pneumoniae, Other Suspect Pathogens, and the Immune System

text: Alzheimer's disease susceptibility genes, APP and gamma-secretase, are involved in the herpes simplex life cycle, and that of other suspect pathogens (C. pneumoniae, H. pylori, C. neoformans, B. burgdorferri, P. gingivalis) or immune defence. Such pathogens promote beta-amyloid deposition and tau phosphorylation and may thus be causative agents, whose effects are conditioned by genes. The antimicrobial effects of beta-amyloid, the localisation of APP/gamma-secretase in immunocompetent dendritic cells, and gamma secretase cleavage of numerous pathogen receptors suggest that this network is concerned with pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer's disease, may well be antibodies to pathogens, due to homology between human autoantigens and pathogen proteins. NGF or tau antibodies promote beta-amyloid deposition, neurofibrillary tangles, or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. Pathogen elimination in the ageing population and removal of culpable autoantibodies might reduce the incidence and offer hope for a cure in this affliction.


title: Experimental infection of a US spike-insertion deletion porcine epidemic diarrhea virus in conventional nursing piglets and cross-protection to the original US PEDV infection

text: Although the original US porcine epidemic diarrhea virus (PEDV) was confirmed as highly virulent by multiple studies, the virulence of spike-insertion deletion (S-INDEL) PEDV strains is undefined. In this study, 3–4 day-old conventional suckling piglets were inoculated with S-INDEL PEDV Iowa106 (4 pig litters) to study its virulence. Two litters of age-matched piglets were inoculated with either the original US PEDV PC21A or mock as positive and negative controls, respectively. Subsequently, all pigs were challenged with the original US PEDV PC21A on 21–29 days post-inoculation (dpi) to assess cross-protection. All S-INDEL Iowa106- and the original US PC21A-inoculated piglets developed diarrhea. However, the severity of clinical signs, mortality (0–75%) and fecal PEDV RNA shedding titers varied among the four S-INDEL Iowa106-inoculated litters. Compared with the original PC21A, piglets euthanized/died acutely from S-INDEL Iowa106 infection had relatively milder villous atrophy, lower antigen scores and more limited intestinal infection. Two of four S-INDEL Iowa106-infected sows and the original PC21A-infected sow showed anorexia and watery diarrhea for 1–4 days. After the original PC21A challenge, a subset (13/16) of S-INDEL Iowa106-inoculated piglets developed diarrhea, whereas all (5/5) and no (0/4) pigs in the mock and original PC21A-inoculated pigs had diarrhea, respectively. Our results suggest that the virulence of S-INDEL PEDV Iowa106 was less than the original US PEDV PC21A in suckling pigs, with 100% morbidity and 18% (6/33) overall (0–75%) mortality in suckling pigs depending on factors such as the sow’s health and lactation and the piglets’ birth weight. Prior infection by S-INDEL Iowa106 provided partial cross-protection to piglets against the original PC21A challenge at 21–29 dpi.


title: Two cases of coronavirus 2019–related cardiomyopathy in pregnancy

text: At our institution, 2 of the initial 7 pregnant patients with confirmed coronavirus disease 2019 severe infection (28.6%; 95% CI, 8.2%–64.1%) developed cardiac dysfunction with moderately reduced left ventricular ejection fractions of 40%–45% and hypokinesis. Viral myocarditis and cardiomyopathy have also been reported in nonpregnant coronavirus disease 2019 patients. A case series of nonpregnant patients with coronavirus disease 2019 found that 33% of those in intensive care developed cardiomyopathy. More data are needed to ascertain the incidence of cardiomyopathy from coronavirus disease 2019 in pregnancy, in all pregnant women with coronavirus disease 2019, and those with severe disease (eg, pneumonia). We suggest an echocardiogram in pregnant women with coronavirus disease 2019 pneumonia, in particular those necessitating oxygen, or those who are critically ill, and we recommend the use of handheld, point-of-care devices where possible to minimize contamination of staff and traditional large echocardiogram machines.


title: Inclusive innovation in telehealth

text: It has been 30 years since the passage of the Americans with Disabilities Act and technological development has drastically changed the future for those with disabilities. As healthcare evolves toward promoting telehealth and patient-centered care, leaders must embrace persons with disabilities and caregivers as valued partners in design and implementation, not as passive “end-users”. We call for a new era of inclusive innovation, a term proposed in this publication to describe accessible technological design for all. The next 30 years of the ADA leading to year 2050, should reflect a new era of access, whereby digital health surmounts geographic, social, and economic barriers toward an inclusive virtual society.


NON-COVID-19 VISITS TO EMERGENCY DEPARTMENTS DURING THE PANDEMIC: THE IMPACT OF FEAR


title: Resource Re-Allocation During the COVID-19 Pandemic in a Suburban Hospital System: Implications for Outpatient Hip and Knee Arthroplasty

text: Abstract The COVID pandemic of 2020 has emerged as a global threat to patients, healthcare providers and to the global economy. Due to this particular novel and highly infectious strain of coronavirus, the rapid community spread and clinical severity of the subsequent respiratory syndrome created a substantial strain on hospitals and healthcare systems around the world. The rapid surge of patients presenting over a small time period for emergent clinical care, admission to the hospital and intensive care units with many requiring mechanically assisted ventilators for respiratory support demonstrated the potential to overwhelm healthcare workers, hospitals and healthcare systems. The purpose of our article is to describe an effective system for re-deployment of healthcare supplies, resources and personnel to hospitals within a suburban academic hospital system to optimize the care of COVID patients, while treating orthopaedic patients in an equally ideal setting to maximize their surgical and clinical care. This article will provide a particular focus on the current and future role of a specialty hip and knee hospital and its partnering ambulatory surgery center in the context of an outpatient arthroplasty program.


title: Assessment of N95 respirator decontamination and re-use for SARS-CoV-2

text: The unprecedented pandemic of SARS-CoV-2 has created worldwide shortages of personal protective equipment, in particular respiratory protection such as N95 respirators. SARS-CoV-2 transmission is frequently occurring in hospital settings, with numerous reported cases of nosocomial transmission highlighting the vulnerability of healthcare workers. In general, N95 respirators are designed for single use prior to disposal. Here, we have analyzed four readily available and often used decontamination methods: UV, 70% ethanol, 70C heat and vaporized hydrogen peroxide for inactivation of SARS-CoV-2 on N95 respirators. Equally important we assessed the function of the N95 respirators after multiple wear and decontamination sessions.


Receptor-Independent Infection of Mouse Hepatitis Virus: Analysis by Spinoculation


title: The psychiatric impact of the novel coronavirus outbreak

text: • We must be aware of the challenge and concerns brought by 2019-nCoV. Every effort should be put to understand and control the disease. • Patients with confirmed or suspected 2019-nCoV (new coronavirus disease) may experience fear of the consequences of being infected with a potentially fatal new virus, and those in quarantine might experience boredom, loneliness, and anger. • In the intervention with staff and patients, we found the stress-adaptation model particularly relevant.


title: Mouse Models as Resources for Studying Infectious Diseases

text: Abstract Mouse models are important tools both for studying the pathogenesis of infectious diseases and for the preclinical evaluation of vaccines and therapies against a wide variety of human pathogens. The use of genetically defined inbred mouse strains, humanized mice, and gene knockout mice has allowed the research community to explore how pathogens cause disease, define the role of specific host genes in either controlling or promoting disease, and identify potential targets for the prevention or treatment of a wide range of infectious agents. This review discusses several of the most commonly used mouse model systems, as well as new resources such as the Collaborative Cross as models for studying infectious diseases.


title: A novel immunity system for bacterial nucleic acid degrading toxins and its recruitment in various eukaryotic and DNA viral systems

text: The use of nucleases as toxins for defense, offense or addiction of selfish elements is widely encountered across all life forms. Using sensitive sequence profile analysis methods, we characterize a novel superfamily (the SUKH superfamily) that unites a diverse group of proteins including Smi1/Knr4, PGs2, FBXO3, SKIP16, Syd, herpesviral US22, IRS1 and TRS1, and their bacterial homologs. Using contextual analysis we present evidence that the bacterial members of this superfamily are potential immunity proteins for a variety of toxin systems that also include the recently characterized contact-dependent inhibition (CDI) systems of proteobacteria. By analyzing the toxin proteins encoded in the neighborhood of the SUKH superfamily we predict that they possess domains belonging to diverse nuclease and nucleic acid deaminase families. These include at least eight distinct types of DNases belonging to HNH/EndoVII- and restriction endonuclease-fold, and RNases of the EndoU-like and colicin E3-like cytotoxic RNases-folds. The N-terminal domains of these toxins indicate that they are extruded by several distinct secretory mechanisms such as the two-partner system (shared with the CDI systems) in proteobacteria, ESAT-6/WXG-like ATP-dependent secretory systems in Gram-positive bacteria and the conventional Sec-dependent system in several bacterial lineages. The hedgehog-intein domain might also release a subset of toxic nuclease domains through auto-proteolytic action. Unlike classical colicin-like nuclease toxins, the overwhelming majority of toxin systems with the SUKH superfamily is chromosomally encoded and appears to have diversified through a recombination process combining different C-terminal nuclease domains to N-terminal secretion-related domains. Across the bacterial superkingdom these systems might participate in discriminating `self’ or kin from `non-self’ or non-kin strains. Using structural analysis we demonstrate that the SUKH domain possesses a versatile scaffold that can be used to bind a wide range of protein partners. In eukaryotes it appears to have been recruited as an adaptor to regulate modification of proteins by ubiquitination or polyglutamylation. Similarly, another widespread immunity protein from these toxin systems, namely the suppressor of fused (SuFu) superfamily has been recruited for comparable roles in eukaryotes. In animal DNA viruses, such as herpesviruses, poxviruses, iridoviruses and adenoviruses, the ability of the SUKH domain to bind diverse targets has been deployed to counter diverse anti-viral responses by interacting with specific host proteins.


title: Overexpression of the nucleocapsid protein of Middle East respiratory syndrome coronavirus up-regulates CXCL10

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory diseases in humans and has a high mortality rate. During infection, MERS-CoV regulates several host cellular processes including antiviral response genes. In order to determine if the nucleocapsid protein of MERS-CoV (MERS-N) plays a role in viral–host interactions, a murine monoclonal antibody was generated so as to allow detection of the protein in infected cells as well as in overexpression system. Then, MERS-N was stably overexpressed in A549 cells, and a PCR array containing 84 genes was used to screen for genes transcriptionally regulated by it. Several up-regulated antiviral genes, namely TNF, IL6, IL8, and CXCL10, were selected for independent validation in transiently transfected 293FT cells. Out of these, the overexpression of MERS-N was found to up-regulate CXCL10 at both transcriptional and translational levels. Interestingly, CXCL10 has been reported to be up-regulated in MERS-CoV infected airway epithelial cells and lung fibroblast cells, as well as monocyte-derived macrophages and dendritic cells. High secretions and persistent increase of CXCL10 in MERS-CoV patients have been also associated with severity of disease. To our knowledge, this is the first report showing that the MERS-N protein is one of the contributing factors for CXCL10 up-regulation during infection. In addition, our results showed that a fragment consisting of residues 196–413 in MERS-N is sufficient to up-regulate CXCL10, while the N-terminal domain and serine-arginine (SR)-rich motif of MERS-N do not play a role in this up-regulation.


title: Enhanced Expression and Purification of Membrane Proteins by SUMO Fusion in Escherichia coli

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) membrane protein and 5-lipoxygenase-activating protein (FLAP) are among a large number of membrane proteins that are poorly expressed when traditional expression systems and methods are employed. Therefore to efficiently express difficult membrane proteins, molecular biologists will have to develop novel or innovative expression systems. To this end, we have expressed the SARS-CoV M and FLAP proteins in Escherichia coli by utilizing a novel gene fusion expression system that takes advantage of the natural chaperoning properties of the SUMO (small ubiquitin-related modifier) tag. These chaperoning properties facilitate proper protein folding, which enhances the solubility and biological activity of the purified protein. In addition to these advantages, we found that SUMO Protease 1, can cleave the SUMO fusion high specificity to generate native protein. Herein, we demonstrate that the expression of FLAP and SARS-CoV membrane proteins are greatly enhanced by SUMO fusions in E. coli.


title: Best practices for standardized performance testing of infrared thermographs intended for fever screening

text: Infrared (IR) modalities represent the only currently viable mass fever screening approaches for outbreaks of infectious disease pandemics such as Ebola virus disease and severe acute respiratory syndrome. Non-contact IR thermometers (NCITs) and IR thermographs (IRTs) have been used for fever screening in public areas such as airports. While NCITs remain a more popular choice than IRTs, there has been increasing evidences in the literature that IRTs can provide great accuracy in estimating body temperature if qualified systems are used and appropriate procedures are consistently applied. In this study, we addressed the issue of IRT qualification by implementing and evaluating a battery of test methods for objective, quantitative assessment of IRT performance based on a recent international standard (IEC 80601-2-59). We tested two commercial IRTs to evaluate their stability and drift, image uniformity, minimum resolvable temperature difference, and radiometric temperature laboratory accuracy. Based on these tests, we illustrated how experimental and data processing procedures could affect results, and suggested methods for clarifying and optimizing test methods. Overall, the insights into thermograph standardization and acquisition methods provided by this study may improve the utility of IR thermography and aid in comparing IRT performance, thus improving the potential for producing high quality disease pandemic countermeasures.


Allium fistulosum congee as a home remedy to ward off the corona virus at an early stage


Respiratory protection for healthcare workers treating Ebola virus disease (EVD): Are facemasks sufficient to meet occupational health and safety obligations?


COVID-19 and diabetes mellitus: what we know, how our patients should be treated now, and what should happen next


title: Isolation and Full-Length Genome Characterization of SARS-CoV-2 from COVID-19 Cases in Northern Italy

text: In December 2019, the novel coronavirus Severe Acquired Respiratory Syndrome SARS-CoV-2 emerged in the city of Wuhan in the Hubei province, People's Republic of China, as the etiologic agent of coronavirus disease 2019 (COVID-19), which has hence spread worldwide causing a global pandemic (1-3).….


title: Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification

text: Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30–45 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30–45 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.


title: Characterization and anti-inflammation role of swine IFITM3 gene

text: IFITM3 is involved in cell adhesion, apoptosis, immune, and antivirus activity. Furthermore, IFITM3 gene has been considered as a preferential marker for inflammatory diseases, and positive correlation to pathological grades. Therefore, we assumed that IFITM3 was regulated by different signal pathways. To better understand IFITM3 function in inflammatory response, we cloned swine IFITM3 gene, and detected IFITM3 distribution in tissues, as well as characterized this gene. Results indicated that the length of swine IFITM3 gene was 438 bp, encoding 145 amino acids. IFITM3 gene expression abundance was higher in spleen and lungs. Moreover, we next constructed the eukaryotic expression vector PBIFM3 and transfected into PK15 cells, finally obtained swine IFITM3 gene stable expression cell line. Meanwhile, we explored the effects of LPS on swine IFITM3 expression. Results showed that LPS increased IFITM3 mRNA abundance and exhibited time-dependent effect for LPS treatment. To further demonstrate the mechanism that IFITM3 regulated type I IFNs production, we also detected the important molecules expression of TLR4 signaling pathway. In transfected and non-transfected IFITM3 PK15 cells, LPS exacerbated the relative expression of TLR4-NFκB signaling molecules. However, the IFITM3 overexpression suppressed the inflammatory development of PK15 cells. In conclusion, these data indicated that the overexpression of swine IFITM3 could decrease the inflammatory response through TLR4 signaling pathway, and participate in type I interferon production. These findings may lead to an improved understanding of the biological function of IFITM3 in inflammation.


docid: suozxaol

title: Pandemic in Melbourne


title: Expression, purification, and characterization of SARS coronavirus RNA polymerase

text: Abstract The RNA-dependent RNA polymerase (RdRp) of SARS coronavirus (SARS-CoV) is essential for viral replication and a potential target for anti-SARS drugs. We report here the cloning, expression, and purification of the N-terminal GST-fused SARS-CoV RdRp and its polymerase catalytic domain in Escherichia coli. During purification, the full-length GST-RdRp was found to cleave into three main fragments: an N-terminal p12 fragment, a middle p30 fragment, and a C-terminal p64 fragment comprising the catalytic domain, presumably due to bacterial proteases. Biochemical assays show that the full-length GST-RdRp has RdRp activity and the p64 and p12 fragments form a complex that exhibits comparable RdRp activity, whereas the GST-p64 protein has no activity, suggesting that the p12 domain is required for polymerase activity possibly via involvement in template-primer binding. Nonnucleoside HIV-1 RT inhibitors are shown to have no evident inhibitory effect on SARS-CoV RdRp activity. This work provides a basis for biochemical and structural studies of SARS-CoV RdRp and for development of anti-SARS drugs.


Covid-19: roundup of latest news.


title: Mapping a Neutralizing Epitope on the SARS Coronavirus Spike Protein: Computational Prediction Based on Affinity-selected Peptides

text: Rapid elucidation of neutralizing antibody epitopes on emerging viral pathogens like severe acute respiratory syndrome (SARS) coronavirus (CoV) or highly pathogenic avian influenza H5N1 virus is of great importance for rational design of vaccines against these viruses. Here we combined screening of phage display random peptide libraries with a unique computer algorithm “Mapitope” to identify the discontinuous epitope of 80R, a potent neutralizing human anti-SARS monoclonal antibody against the spike protein. Using two different types of random peptide libraries which display cysteine-constrained loops or linear 13–15-mer peptides, independent panels containing 42 and 18 peptides were isolated, respectively. These peptides, which had no apparent homologous motif within or between the peptide pools and spike protein, were deconvoluted into amino acid pairs (AAPs) by Mapitope and the statistically significant pairs (SSPs) were defined. Mapitope analysis of the peptides was first performed on a theoretical model of the spike and later on the genuine crystal structure. Three clusters (A, B and C) were predicted on both structures with remarkable overlap. Cluster A ranked the highest in the algorithm in both models and coincided well with the sites of spike protein that are in contact with the receptor, consistent with the observation that 80R functions as a potent entry inhibitor. This study demonstrates that by using this novel strategy one can rapidly predict and identify a neutralizing antibody epitope, even in the absence of the crystal structure of its target protein.


title: The challenges of implementing an integrated One Health surveillance system in Australia

text: As 75 per cent of emerging infectious diseases are of animal origin, a One Health approach that integrates the health of humans, animals and the environment could provide an earlier opportunity for zoonotic disease detection and prevention. In Australia, human, animal and ecological health are managed by separate sectors with limited communication. This study aims to explore how professionals in these fields perceive a One Health approach to zoonotic disease surveillance, aiming to identify the challenges to the implementation of an integrated system in Australia. Using a qualitative research method, ten semistructured interviews were conducted with academic experts to gain insight into the possibility of developing an integrated surveillance system in Australia. A thematic analysis of the data was undertaken. Findings showed the absence of a clear definition and subsequent vision for the future of One Health act as a barrier to interdisciplinary collaboration, and that siloed approaches by different sectors restrict the ability for professionals to work collaboratively across disciplines. An understanding of disease transmission was considered by participants to be a necessary requirement for a successful One Health approach. Finally, participants considered political will an essential requirement for the integration of surveillance systems. This study demonstrates that for a One Health approach to be implemented in an Australian setting, those working in the fields of human, animal and ecological health must agree on several aspects. The establishment of a formal governance body with representatives from each sector could assist in overcoming long‐standing barriers of privacy and distrust. Further, developing interdisciplinary training in One Health concepts for medical, environmental and veterinary students may encourage cross‐disciplinary collaboration. Finally, demonstrating to policymakers the economic benefit of improved and timely detection of zoonoses may help in facilitating a structured One Health approach to disease surveillance in Australia.


title: Pasteurization of chicken litter with steam and quicklime to reduce Salmonella Typhimurium

text: SUMMARY The nursery industry pasteurizes soil with steam and quicklime to reduce plant pathogens. The mechanism of action for quicklime is the resulting exothermic reaction that occurs when the chemical interacts with water and its ability to increase pH levels. These treatments may also reduce pathogens in a commercial poultry house. In this study, a steam sterilization cart simulated conditions used by the nursery industry to treat litter inoculated with Salmonella enterica serovar Typhimurium. A homogenized sample of litter was exposed to steam for 0, 5, 30, or 120 min. Quicklime was used at concentrations of 0 (control), 2.5, 5.0, or 10.0%. All steam treatments, with or without quicklime, significantly reduced Salmonella Typhimurium colonization by at least 3 orders of magnitude. Significant reductions were also observed in the treatments with quicklime alone. Both the steam and the quicklime treatments often reduced colonization to undetectable levels, even when samples were enriched. Therefore, we demonstrated 2 novel techniques for reducing Salmonella Typhimurium in poultry litter. Soil pasteurization potentially offers an environmentally sound means of reducing the pathogens present in used poultry litter.


title: Targeting the Vasoprotective Axis of the Renin-Angiotensin System: A Novel Strategic Approach to Pulmonary Hypertensive Therapy

text: A decade has passed since the discovery of angiotensin-converting enzyme 2 (ACE2), a component of the ACE2–angiotensin (Ang)-(1-7)–Mas counterregulatory axis of the renin angiotensin system (RAS). ACE2 is considered an endogenous regulator of the vasoconstrictive, proliferative, fibrotic, and proinflammatory effects of the ACE–Ang II–angiotensin II type 1 receptor (AT(1)R) axis. Both animal and clinical studies have emerged to define a role for ACE2 in pulmonary arterial hypertension (PAH). There is scientific evidence supporting the concept that ACE2 maintains the RAS balance and plays a protective role in PAH. The activation of pulmonary ACE2 could influence the pathogenesis of PAH and serve as a novel therapeutic target in PAH. Current therapeutic strategies and interventions have limited success, and PAH remains a fatal disease. Thus, more research that establishes the novel therapeutic potential and defines the mechanism of the ACE2–Ang-(1-7)–Mas counterregulatory axis in PAH is needed.


title: Comment et pourquoi adapter le masque Décathlon EasyBreath® pour les soignants prenant en charge des patients infectés par le SARS-CoV-2?

text: Résumé Durant l’épidémie de COVID-19, les équipements de protection personnelle sont largement utilisés pour limiter l’infection des soignants. Des solutions innovantes ont été décrites pour pallier les difficultés d’approvisionnement. L’adaptation du masque de plongée EasyBreath® par l’équipe de Prakash a été médiatisée et diffusée. Nous présentons 4 dispositifs imprimés en 3D que nous avons modifiés par rapport au design initial innovant afin de nous adapter aux contraintes locales. Nous avons testé le masque en condition chirurgicale. Les modifications apportées garantissent une meilleure ergonomie, visibilité et capacités de communication, mais elles n’ont pas d’homologation d’utilisation et ne peuvent donc être recommandées qu’en l’absence de solution alternative validée. L’impression 3D est un outil de première importance dans la production de dispositifs à usage médical en situation de crise sanitaire.


title: Respiratory virus infections: Understanding COVID-19

text: Respiratory viruses affect us throughout our lives, from infancy to old age, causing illnesses ranging from a common cold to severe pneumonia. They belong to several virus families, and although many features of infection with these diverse viruses are shared, some have unique characteristics. Here we explain what happens when we are infected by respiratory viruses, including SARS-CoV-2, which causes COVID-19.


title: Chapter 20 Reproductive management of poultry

text: Abstract Based on data from the UN's Food and Agricultural Organization, about 120 million metric tons of poultry meat were produced globally in 2016. In addition, about 82 million metric tons of eggs were produced. One of the bases for this production is the reproductive efficiency of today's poultry. This, in turn, is due to their inherent reproductive physiology, intensive genetic selection and advances in husbandry/management. The system of reproduction in males in largely similar to that in mammals except that there is no descent of testes. In females, there are marked differences with there being a single ovary and oviduct; the latter being the name of the differentiated entire Müllerian duct. Moreover, females produce eggs with a yolky oocyte surrounded by albumen, membranes and shell. Among the most successful reproductive management techniques are optimizing photoperiod, light intensity and nutrition. Widespread employment of these has allowed maximizing production. Laying hens can be re-cycled toward the end egg production. Other aspects of reproductive management in poultry include the following: artificial insemination (almost exclusively employed in turkeys) and approaches to reduce broodiness together with cage free (colony), conventional, enriched and free-range systems.


title: COVID-19 impact assessment on the French radiological centers: a nationwide survey

text: PURPOSE: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. MATERIALS AND METHODS: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CT(covid)) and whole chest CT scan activities (CT(chest)) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson’s test. RESULTS: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CT(chest) activity per radiologic structure ranged from 75.8 ± 133 (0–1444) on week 12 to 99.3 ± 138.6 (0–1147) on week 13. Mean ratio of CT(covid) on CT(chest) varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CT(covid) (r = 0.73, p = 3.10(−16)) but no link with the number of positive RT-PCR results. CONCLUSION: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients. KEY POINTS: • Over the 4-week survey period, 117,686 chest CT (CT (total) ) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CT (covid) ). • Across the country, the ratio CT (covid) /CT (total) varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00330-020-07035-w) contains supplementary material, which is available to authorized users.


title: A multisite, randomized field trial to evaluate the influence of lactoferrin on the morbidity and mortality of dairy calves with diarrhea

text: ABSTRACT Diarrhea is one of the most common causes of antimicrobial use and mortality in young calves. To reduce antimicrobial use and resistance on dairy farms, research on alternative therapies for calf diarrhea is necessary. Our laboratory previously conducted a randomized clinical trial investigating the effectiveness of lactoferrin, an iron-binding protein found in colostrum, as a treatment for calf diarrhea. The trial showed significantly reduced calf mortality in diarrheic calves that were administered lactoferrin. Thus, the objective of this study was to corroborate the results of our prior clinical trial across multiple farms and to investigate the effect of lactoferrin on the morbidity and mortality of preweaned calves with naturally occurring cases of diarrhea. This randomized field trial was conducted on 5 commercial dairy farms in Ohio. In total, 485 calves (≤21 d of age) were enrolled at first diarrhea diagnosis (fecal score ≥2 defined as loose to watery) and randomly assigned to receive an oral dose of lactoferrin (3 g of lactoferrin powder dissolved in 30 mL of water) or 30 mL of water (control) once daily for 3 consecutive days. Health assessments were conducted on the day of diarrhea diagnosis (d 0) and 1, 2, 3, 7, 14, 21, 28, and 35 d following diagnosis. Producer records of disease treatment and mortality were collected 120 d following diagnosis. A Poisson regression model was used to test differences between treatments in disease frequency through 35 d post-diarrhea diagnosis and the incidence risk of treatment and mortality risk 120 d post-diarrhea diagnosis; the model controlled for calf age at enrollment, farm, and treatment. Median calf age at enrollment was 11 d and ranged from 1 to 26 d of age. At study enrollment, 51.3% (123/240) and 52.2% (128/245) of calves in the control and lactoferrin treatment groups, respectively, were diagnosed with severe diarrhea (fecal score = 3). The frequency of disease (diarrhea, dehydration, depression, signs of respiratory disease) through 35 d following diarrhea diagnosis was not significantly different for calves in the lactoferrin and control groups. Overall mortality risk for enrolled calves was 9.9%, and 10.7% (22/243) and 9.1% (26/242) of calves in the lactoferrin and control groups, respectively, died or were culled in the 120 d following diarrhea diagnosis. The relative risk of death or culling did not differ between treatment groups, however. Therefore, as performed in this study, lactoferrin as a treatment for calf diarrhea was not beneficial.


title: RNA structures with pseudo-knots: Graph-theoretical, combinatorial, and statistical properties

text: The secondary structures of nucleic acids form a particularly important class of contact structures. Many important RNA molecules, however, contain pseudo-knots, a structural feature that is excluded explicitly from the conventional definition of secondary structures. We propose here a generalization of secondary structures incorporating ‘non-nested’ pseudo-knots, which we call bi-secondary structures, and discuss measures for the complexity of more general contact structures based on their graph-theoretical properties. Bi-secondary structures are planar trivalent graphs that are characterized by special embedding properties. We derive exact upper bounds on their number (as a function of the chain length n) implying that there are fewer different structures than sequences. Computational results show that the number of bi-secondary structures grows approximately like 2.35(n). Numerical studies based on kinetic folding and a simple extension of the standard energy model show that the global features of the sequence-structure map of RNA do not change when pseudo-knots are introduced into the secondary structure picture. We find a large fraction of neutral mutations and, in particular, networks of sequences that fold into the same shape. These neutral networks percolate through the entire sequence space.


title: Characterization of pantropic canine coronavirus from Brazil

text: Abstract Characterization of canine coronavirus (CCoV) strains currently in circulation is essential for understanding viral evolution. The aim of this study was to determine the presence of pantropic CCoV type IIa in tissue samples from five puppies that died in Southern Brazil as a result of severe gastroenteritis. Reverse-transcriptase PCR was used to generate amplicons for sequence analysis. Phylogenetic analysis of the CCoV-IIa strains indicated that they were similar to those found in other countries, suggesting a common ancestor of these Brazilian isolates. This is the first report of pantropic CCoV-II in puppies from Latin America and our findings highlight that CCoV should be included as a differential diagnosis when dogs present with clinical signs and lesions typically seen with canine parvovirus infection.


title: The Threat and Response to Infectious Diseases (Revised)

text: The threat from microorganisms is complex, and the approaches for reducing the challenges the world is facing are also multifaceted, but a combination approach including several simple steps can make a difference and reduce morbidity and mortality and the economic cost of fighting infectious diseases. This paper discusses the continually evolving infectious disease landscape, contributing factors in the rise of the threat, reasons for optimism, and the policies, technologies, actions, and institutions that might be harnessed to further reduce the dangers introduced by pathogens. It builds upon and updates the work of other authors that have recognized the dangers of emerging and re-emerging pathogens and have explored and documented potential solutions.


title: Critical reviews of immunotheranostics

text: Immunity is the most critical and well-regulated protection to the body. Immunity is implicated in a wide range of diseases and serves as the foundation for immunotherapy. Immunotheranostics is the idea of improving immunotherapy through the organic integration of therapeutic, diagnostic, and screening technologies. This special issue collects reviews and opinions from prominent contributors in the immunotheranostic field who represent highly diversified research expertise. The immunotherapeutics discussed in this issue range from small molecules, peptides, antibodies, nanoparticles, and to cells. Discussions from the therapeutic development perspective are accompanied by opinions from the biology and medicine aspects. Further, there are reviews about different types of imaging technologies and their applications in immunotherapy. Lastly, one review raises attention to mass spectrometry for its utilization in the diagnosis and assessment for immunotherapy. In summary, this special issue is a showcase for what is happening in immunotheranostics. Moreover, it is also a justified wish list for what should and will happen in immunotheranostics.


title: RNA silencing of rotavirus gene expression

text: Abstract RNA interference (RNAi) is a double-stranded RNA (dsRNA)-triggered mechanism for suppressing gene expression, which is conserved in evolution and has emerged as a powerful tool to study gene function. Rotaviruses, the leading cause of severe diarrhea in young children, are formed by three concentric layers of protein, and a genome composed of 11 segments of dsRNA. Here, we show that the RNAi machinery can be triggered to silence rotavirus gene expression by sequence-specific short interfering RNAs (siRNAs). RNAi is also useful for the study of the virus-cell interactions, through the silencing of cellular genes that are potentially important for the replication of the virus. Interestingly, while the translation of mRNAs is readily stopped by the RNAi machinery, the viral transcripts involved in virus genome replication do not seem to be susceptible to RNAi. Since gene silencing by RNAi is very efficient and specific, this system could become a novel therapeutic approach for rotavirus and other virus infections, once efficient methods for in vivo delivery of siRNAs are developed. Although the use of RNAi as an antiviral therapeutic tool remains to be demonstrated, there is no doubt that this technology will influence drastically the way postgenomic virus research is conducted.