title: ACTUALIZACION EN COVID-19 Y ENFERMEDAD HEPÁTICA

text: Resumen La pandemia producida por SARS-CoV-2 ha supuesto uno de los mayores desafíos del sistema sanitario español. El impacto del virus sobre el hígado no es bien conocido, pero en pacientes con enfermedades hepáticas crónicas, especialmente en estadios avanzados, puede comprometer de forma crítica la supervivencia y desencadenar descompensaciones. El tratamiento en esta subpoblación es complejo por la potencial hepatotoxicidad de algunos fármacos empleados. Más allá, la pandemia también ha impactado negativamente sobre aquellos con enfermedades hepáticas que no han adquirido la enfermedad, ya que la redistribución de los recursos humanos y materiales hacia la atención de pacientes con COVID-19, ha provocado una merma en su tratamiento, diagnóstico y seguimiento que a buen seguro tendrá consecuencias negativas en el futuro. La reorganización eficiente de las unidades de Hepatología es una necesidad de primer orden para aminorar el impacto de la pandemia sobre una población tan vulnerable como los pacientes con hepatopatía. Abstract The SARS-CoV-2 pandemic has proven to be a serious challenge for the Spanish healthcare system. The impact of the virus on the liver is not well known, but in patients with chronic liver disease, mostly in advanced stages, it can critically compromise survival and trigger decompensation. Treatment in this subpopulation is complex due to the potential hepatotoxicity of some of the medicinal products used. Moreover, the pandemic has also negatively impacted patients with liver disease who have not contracted COVID-19, since the reallocation of human and material resources to the care of patients with the virus has resulted in a decrease in the treatment, diagnosis and follow-up of patients with liver disease, which will surely have negative consequences in the near future. Efficient reorganisation of hepatology units is a priority to minimise the impact of the pandemic on a population as vulnerable as liver disease patients.


title: Antibody-profiling technologies for studying humoral responses to infectious agents

text: Analyses of humoral responses against different infectious agents are critical for infectious disease diagnostics, understanding pathogenic mechanisms, and the development and monitoring of vaccines. While ELISAs are often used to measure antibody responses to one or several targets, new antibody-profiling technologies, such as protein microarrays, can now evaluate antibody responses to hundreds, or even thousands, of recombinant antigens at one time. These large-scale studies have uncovered new antigenic targets, provided new insights into vaccine research and yielded an overview of immunoreactivity against almost the entire proteome of certain pathogens. However, solid-phase antigen arrays also have drawbacks that limit the type of information obtained, including suboptimal detection of conformational epitopes, high backgrounds due to impure antigens and a narrow dynamic range of detection. We have developed a solution-phase antibody-profiling technology, luciferase immunoprecipitation systems (LIPS), which harnesses light-emitting recombinant antigen fusion proteins to quantitatively measure patient antibody titers. Owing to the highly linear light output of the luciferase reporter, some antibodies can be detected without serum dilution in a dynamic range of detection often spanning seven orders of magnitude. When LIPS is applied iteratively with multiple target antigens, a high-definition antibody profile is obtained. Here, we discuss the application of these different antibody-profiling technologies and their associated limitations with particular emphasis on protein microarrays. We also describe LIPS in detail and discuss several clinically relevant uses of the technology. Together, these new technologies offer new tools for understanding humoral responses to known and emerging infectious agents.


title: The Synergistic Interaction of Interferon Types I and II Leads to Marked Reduction in Severe Acute Respiratory Syndrome-Associated Coronavirus Replication and Increase in the Expression of mRNAs for Interferon-Induced Proteins

text: Interferon (IFN)-α, -β and -γ have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-α or -β) and IFN-γ for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-γ parallels the marked increase in 2′-5′-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-α or -β and IFN-γ compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.


title: Emergency Medical Services Utilization during an Outbreak of Severe Acute Respiratory Syndrome (SARS) and the Incidence of SARS‐associated Coronavirus Infection among Emergency Medical Technicians

text: Objectives: This was a study to evaluate the utilization of emergency medical services (EMS) systems during the outbreak of severe acute respiratory syndrome (SARS), and to assess the incidence of infection among emergency medical technicians (EMTs). Methods:This was a prospective, observational study conducted in the EMS system of Taipei, Taiwan. Probable/suspect cases of SARS were defined by World Health Organization criteria. SARS‐related transports were categorized into 1) requests from hospitals for probable/suspect cases of SARS, 2) quarantined individuals, and 3) febrile persons. City ambulances were organized into teams A, B, and C for transports of different perceived risks. Data on the EMS volume, the transport category, the final SARS status of patients, and the EMT responsible for the transports were collected. The EMS projected volume was computed by previous years' data and compared with that collected. The SARS incidence among EMTs was assessed by investigating probable SARS (P‐SARS) and by surveying the seroprevalence of SARS‐associated coronavirus (SARS‐CoV) antibody. Results: From March 18 to June 19, 2003, there were 7,961 EMS transports, similar to the volume projected from previous years (7,506) (95% CI = 6,688 to 8,324). Of these, 1,760 (22.1%) were SARS‐related. When SARS‐related transports were excluded, there was a 12.2% decrease (95% CI = 11.4% to 12.9%) in EMS activities. Requests from hospitals, quarantined individuals, and febrile citizens accounted for 23%, 18%, and 59% of SARS‐related transports. Among the 397 P‐SARS cases in the city of 2.65 million people (incidence 0.01%, 95% CI = 0.01% to 0.02%), 138 (35%) required EMS transports. Two EMTs working in team C, the team with the lowest risk, developed P‐SARS. One of them died soon thereafter. The incidence of P‐SARS was 0.6% (95% CI = 0.2% to 2.2%), or 0.1% (95% CI = 0.03% to 0.4%) per transport. SARS‐CoV serology was available in 74.1% of EMTs who were alive. In addition to the surviving P‐SARS EMT, one EMT from team A, the team with the highest risk, was seropositive. Combining P‐SARS and the seropositive case, three EMTs were infected (incidence 1.3%, 95% CI = 0.4% to 3.6%). No patient transported by the infected EMTs developed SARS. The hospitals serving EMS by the infected EMTs had been involved in a clustered outbreak prior to the EMTs' infections. Conclusions: During the outbreak of SARS, the overall EMS volume did not change significantly, but the non‐SARS EMS activities decreased. Compared with the general population, EMS providers are at higher risk of contracting the SARS virus regardless of different perceived levels of risk. Standard protections and procedures for infection control should be strictly followed during transport and within the hospital environment.


title: Geriatrie in Zeiten von Corona

text: The current corona crisis affects older patients as well as the geriatric infrastructure in all sectors. This article provides an overview about the current state of knowledge on COVID-19 with special consideration of geriatric aspects and the consequences for the geriatric care system.


title: Evaluation of a Barrier to Inhibit Lesser Mealworm (Coleoptera: Tenebrionidae) and Dermestidae Movement in High-Rise, Caged-Layer Poultry Facilities

text: An evaluation of a mechanical barrier to prevent movement of adult and larval lesser mealworm, Alphitobius diaperinus (Panzer); larder beetle, Dermestes lardarius L.; and hide beetle, Dermestes maculatus De Geer was conducted in caged-layer poultry facilities in New York and Maine. The barrier, a plastic collar wrapped around building support posts, proved highly effective at preventing movement of adult lesser mealworms. Significantly more lesser mealworm larvae were recovered from cardboard collar beetle traps placed below both washed and unwashed barriers than from traps placed above washed and unwashed barriers. Similarly, significantly more adult Dermestes were recovered from traps placed below washed barriers than from above both washed and unwashed barriers. The level of fly specking on the barrier was found to have no significant impact on the numbers of adult lesser mealworms and adult and larval Dermestes recovered either above or below barriers. Fly specking level did significantly impact the numbers of lesser mealworm larvae recovered above the barrier. Although washed barriers provided the greatest deterrent to adult lesser mealworms, the presence of the barrier, regardless of the level of fly specking, provided a significant deterrent to beetle climbing success. Washed barriers further reduced climbing success by lesser mealworm larvae by 17%, Dermestes adults by 7–28%, and Dermestes larvae by 33–38%. The high level of climbing observed by adult lesser mealworms suggests that the impact of adult beetle movement toward birds should be considered in its importance in building damage, disease transmission, feed infestation, and bird productivity and health. Observations on cost and maintenance of the barrier are discussed.


title: Significant reduction in hospital admissions for acute exacerbation of chronic obstructive pulmonary disease in Hong Kong during coronavirus disease 2019 pandemic

text: BACKGROUND: Chronic respiratory diseases are risk factors for severe disease in coronavirus disease 2019 (COVID-19). Respiratory tract infection is one of the commonest causes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There has not been evidence suggesting the link between COVID-19 and AECOPD, especially in places with dramatic responses in infection control with universal masking and aggressive social distancing. METHODS: This is a retrospective study to assess the number of admissions of AECOPD in the first three months of 2020 in Queen Mary Hospital with reference to the admissions in past five years. Log-linear model was used for statistical inference of covariates, including percentage of masking, air quality health index and air temperature. RESULTS: The number of admissions for AECOPD significantly decreased by 44.0% (95% CI 36.4%–52.8%, p < 0.001) in the first three months of 2020 compared with the monthly average admission in 2015–2019. Compare to same period of previous years, AECOPD decreased by 1.0% with each percent of increased masking (p < 0.001) and decreased by 3.0% with increase in 1 °C in temperature (p = 0.045). The numbers of admissions for control diagnoses (heart failure, intestinal obstruction and iron deficiency anaemia) in the same period in 2020 were not reduced. CONCLUSIONS: The number of admissions for AECOPD decreased in first three months of 2020, compared with previous years. This was observed with increased masking percentage and social distancing in Hong Kong. We postulated universal masking and social distancing during COVID-19 pandemics both contributed in preventing respiratory tract infections hence AECOPD.


title: Sterile nodular panniculitis with lung and lymph node involvement in a Siberian tiger (Panthera tigris altica)

text: A 2- to 4-year-old uncastrated male Siberian tiger (Panthera tigris altica) bred in a local wild animal park presented with generalized clinical signs including abdominal pain, fever, lethargy, and anorexia, along with subcutaneous nodules along the trunk. The patient subsequently died of chronic, progressive dyspnea despite 45 days of antibiotic treatment. At necropsy, mesenteric fat inflammation and multiple subcutaneous, peritoneal, and intraabdominal nodules were observed. The lungs demonstrated congestion and heavy coagulation, and necrotic foci were observed on the cut surface. Histopathologically, the nodules were identified as granulomatous fatty tissue with numerous lymphocytes, infiltration with lipid-laden macrophages, and fibrosis. These changes were also noted in the lung. The etiology of this condition remains undetermined.


title: M(IL-4) Tissue Macrophages Support Efficient Interferon-Gamma Production in Antigen-Specific CD8(+) T Cells with Reduced Proliferative Capacity

text: CD8(+) cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ activation status influences their antigen presentation function to CD8(+) T cell in models of virus infection. Consequently, we tested how polarization of spleen-derived (Sp)-MΦ impacts direct presentation of viral antigens to influence effector and proliferative CD8(+) T-cell responses. We show that M(IL-4) Sp-MΦ retain MHC-I surface expression and the ability to stimulate IFN-γ production by CTL following peptide stimulation and lymphocytic choriomeningitis virus infection to levels similar to M0 and M(LPS + IFN-γ) MΦ. However, memory CD8(+) T cells cultured in the presence of M(IL-4) MΦ underwent significantly reduced proliferation and produced similar IFN-γ levels as coculturing with M0 or M(LPS + IFN-γ) cells. Thus, these results show a novel ability of polarized MΦ to regulate CD8(+) T-cell proliferation and effector functions during virus infection.


title: San‐Huang‐Xie‐Xin‐Tang extract suppresses hepatitis C virus replication and virus‐induced cyclooxygenase‐2 expression

text: Summary. Chronic hepatitis C virus (HCV) infection is associated with chronic inflammation of liver, which leads to the development of cirrhosis and hepatocellular carcinoma (HCC). Because of severe side effects and only a 50–70% cure rate in genotype 1 HCV‐infected patients upon current standard treatment with pegylated interferon‐α plus ribavirin, new therapeutic regimens are still needed. San‐Huang‐Xie‐Xin‐Tang (SHXT) is a transitional Chinese herbal formula, composed of Rhei rhizoma, Scutellaria radix and Coptidis rhizome, and possesses anti‐inflammatory effect. Here, we describe a (+)‐catechin‐containing fraction extracted from SHXT, referred as SHXT‐frC, exhibited effective inhibition of HCV replication, with selectivity index value (SI; CC(50)/EC(50)) of 84, and displayed synergistic anti‐HCV effects when combined with interferon‐α, HCV protease inhibitor telaprevir or polymerase inhibitor 2′‐C‐methylcytidine. The activation of factor‐κB (NF‐κB) and cyclooxygenase‐2 (COX‐2) signalling pathway has particular relevance to HCV‐associated HCC. SHXT‐frC treatment also caused a concentration‐dependent decrease in the induction of COX‐2 and NF‐κB expression caused by either HCV replication or HCV NS5A protein. Collectively, SHXT‐frC could be an adjuvant treatment for patients with HCV‐induced liver diseases.


title: Asthma: Clinical expression and molecular mechanisms

text: Asthma is a complex disorder that displays heterogeneity and variability in its clinical expression both acutely and chronically. This heterogeneity is influenced by multiple factors including age, sex, socioeconomic status, race and/or ethnicity, and gene by environment interactions. Presently, no precise physiologic, immunologic, or histologic characteristics can be used to definitively make a diagnosis of asthma, and therefore the diagnosis is often made on a clinical basis related to symptom patterns (airways obstruction and hyperresponsiveness) and responses to therapy (partial or complete reversibility) over time. Although current treatment modalities are capable of producing control of symptoms and improvements in pulmonary function in the majority of patients, acute and often severe exacerbations still occur and contribute significantly to both the morbidity and mortality of asthma in all age groups. This review will highlight some of the important clinical features of asthma and emphasize recent advances in both pathophysiology and treatment.


title: Multidisciplinary research priorities for the COVID-19 pandemic: a call for action for mental health science

text: Summary The coronavirus disease 2019 (COVID-19) pandemic is having a profound effect on all aspects of society, including mental health and physical health. We explore the psychological, social, and neuroscientific effects of COVID-19 and set out the immediate priorities and longer-term strategies for mental health science research. These priorities were informed by surveys of the public and an expert panel convened by the UK Academy of Medical Sciences and the mental health research charity, MQ: Transforming Mental Health, in the first weeks of the pandemic in the UK in March, 2020. We urge UK research funding agencies to work with researchers, people with lived experience, and others to establish a high level coordination group to ensure that these research priorities are addressed, and to allow new ones to be identified over time. The need to maintain high-quality research standards is imperative. International collaboration and a global perspective will be beneficial. An immediate priority is collecting high-quality data on the mental health effects of the COVID-19 pandemic across the whole population and vulnerable groups, and on brain function, cognition, and mental health of patients with COVID-19. There is an urgent need for research to address how mental health consequences for vulnerable groups can be mitigated under pandemic conditions, and on the impact of repeated media consumption and health messaging around COVID-19. Discovery, evaluation, and refinement of mechanistically driven interventions to address the psychological, social, and neuroscientific aspects of the pandemic are required. Rising to this challenge will require integration across disciplines and sectors, and should be done together with people with lived experience. New funding will be required to meet these priorities, and it can be efficiently leveraged by the UK's world-leading infrastructure. This Position Paper provides a strategy that may be both adapted for, and integrated with, research efforts in other countries.


title: Seroepidemiological Study on SARS-CoV IgG Antibodies of Different Populations from Several Areas

text: OBJECTIVE: In order to investigate the clinical and epidemiological rules of severe acute respiratory syndrome (SARS), rates and levels SARS coronavirus (SARS-CoV) IgG antibodies of the patients and community populations from several areas were detected. METHODS: Indirect immunofluorescent assay (IFA) and double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) were used to detect the SARS coronavirus-specific IgG antibodies in sera of 1700, including 1453 general populations from Hongkong, Marco, Guangzhou and Peking and 257 SARS patients from Guangzhou and Peking. The dynamics of the serum antibodies of SARS patients were observed from 3 to 360 days after onset of symptoms. RESULTS: 90% of 257 patient serum specimens after 20 days of disease onset showed positive SARS-CoV IgG either using ELISA or IFA. 257 SARS patients, antibodies titers increased steadily in early 4 to 6 months after onset of SARS. The titers of most cases came to the peak in the 6th month. then antibodies titers declined rapidly in some cases. However, all specimens still were positive for SARS-CoV IgG in the 48th month. CONCLUSIONS: This study suggest that few inapparent infectious patients exist during SARS epidemic. Serum IgG antibodies has diagnostic value for SARS in the late course of disease and the antibodies present more than 48 months.


title: Nowo pojawiające się choroby zakaźne w aspekcie bezpieczeństwa krwi

text: The risk of transfusion-related infectious diseases, the markers for which are routinely tested, is extremely low. Recently, however, blood transfusion service faces the challenge from emerging infectious diseases (EIDs), mainly zoonotic origin. Pathogens are microorganisms, mostly viruses, that usually require vectors for their transmission to humans. The relation of some EIDs to transfusion has been proved, in other cases it is considered likely. The paper presents views on EIDs etiology and spread and explains the epidemiologic basic terminology. It describes the principles and methods of EIDs risk assessment as well as prioritization of EIDs with regard to transfusion risk. It outlines the principles of international cooperation and rapid response to newly emerging threats. More attention is devoted to such diseases as West Nile fever, malaria, dengue and chikungunya which are recently a real epidemiological threat. Preventive measures to reduce the threat of EIDs transmission have also been discussed as well as their impact on the safety and supply of blood and blood components.


title: Clinical Chemistry through Clinical Chemistry: A Journal Timeline

text: The establishment of the modern discipline of clinical chemistry was concurrent with the foundation of the journal Clinical Chemistry and that of the American Association for Clinical Chemistry in the late 1940s and early 1950s. To mark the 50th volume of this Journal, I chronicle and highlight scientific milestones, and those within the discipline, as documented in the pages of Clinical Chemistry. Amazing progress has been made in the field of laboratory diagnostics over these five decades, in many cases paralleling—as well as being bolstered by—the rapid pace in the development of computer technologies. Specific areas of laboratory medicine particularly well represented in Clinical Chemistry include lipids, endocrinology, protein markers, quality of laboratory measurements, molecular diagnostics, and general advances in methodology and instrumentation.


title: Les virus bougent: périls planétaires

text: SUMMARY Emerging viral diseases are nothing new. Smallpox probably reached Europe from Asia in the 5th century, and yellow fever emerged in the Americas during the 16th century as a consequence of the African slave trade. Dengue fever arose simultaneously in South-East Asia, Africa, and North America during the 18th century. In 1918–1919 the so-called Spanish ‘flu spread like wildfire through all five continents, killing between 25 and 40 million people. The second half of the 20th century saw the emergence of HIV/AIDS (1981), among other viral diseases. Even more worrying is the fact that emerging and re-emerging viral diseases have had a tendency to spread more quickly and more widely during the last decade, invading whole countries and continents; witness the recent outbreaks of Nipah virus, West Nile, Rift Valley fever, SARS, monkeypox, avianflu (H5N1) and Chikungunya. The complex factors underlying these new trends are briefly discussed.


Serological Evidence of Bat SARS-Related Coronavirus Infection in Humans, China


title: Establishing a conceptual model for photochemical ozone pollution in subtropical Hong Kong

text: Abstract Photochemical ozone (O3) formation is related to its precursors and meteorological conditions. A conceptual model of O3 air pollution is developed based on the analysis of data obtained at Tung Chung (TC) in Hong Kong. By comparing meteorological parameters between O3 and non-O3 episode days, it was found that high temperatures, strong solar radiation, low wind speeds and relative humidity, northeasterly and/or northwesterly prevailing winds were favorable for the O3 formation, while tropical cyclones were most conducive to the occurrence of O3 episodes. Backward trajectories simulation and graphical illustration of O3 pollution suggested that super-regional (i.e. central and eastern China) and regional (i.e. Pearl River Delta, southern China) transport was another factor that contributed to high O3 levels in Hong Kong. The photochemical O3 formation, generally VOC-limited in Hong Kong, was controlled by a small number of volatile organic compounds (VOCs). Furthermore, the positive matrix factorization (PMF) simulation suggested that solvent usage and vehicular emissions are the major contributors to ambient VOCs in Hong Kong. Finally, this paper presents recommendations for further O3 research and implementation of O3 control strategies.


title: Expert consensus on the procedure of interventional diagnosis and treatment of cancer patients during the COVID-19 epidemic

text: Abstract Since December 2019, coronavirus disease (COVID-19) has spread rapidly from Wuhan, Hubei province, to other regions of China. To reduce and prevent cross-over infections in the interventional diagnosis and treatment of tumor patients. The Interventional Oncology Branch of the China Anti-Cancer Association organized specialists to compile the corresponding expert consensus. The consensus summarizes the critical points for COVID-19 prevention, focusing on the management of outpatients, inpatients, and interventional operating room in this particular time.


title: A novel application of small-angle scattering techniques: Quality assurance testing of virus quantification technology

text: Abstract Small-angle scattering (SAS) techniques, like small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), were used to measure and thus to validate the accuracy of a novel technology for virus sizing and concentration determination. These studies demonstrate the utility of SAS techniques for use in quality assurance measurements and as novel technology for the physical characterization of viruses.


title: Programmed Ribosomal Frameshift Alters Expression of West Nile Virus Genes and Facilitates Virus Replication in Birds and Mosquitoes

text: West Nile virus (WNV) is a human pathogen of significant medical importance with close to 40,000 cases of encephalitis and more than 1,600 deaths reported in the US alone since its first emergence in New York in 1999. Previous studies identified a motif in the beginning of non-structural gene NS2A of encephalitic flaviviruses including WNV which induces programmed −1 ribosomal frameshift (PRF) resulting in production of an additional NS protein NS1′. We have previously demonstrated that mutant WNV with abolished PRF was attenuated in mice. Here we have extended our previous observations by showing that PRF does not appear to have a significant role in virus replication, virion formation, and viral spread in several cell lines in vitro. However, we have also shown that PRF induces an over production of structural proteins over non-structural proteins in virus-infected cells and that mutation abolishing PRF is present in ∼11% of the wild type virus population. In vivo experiments in house sparrows using wild type and PRF mutant of New York 99 strain of WNV viruses showed some attenuation for the PRF mutant virus. Moreover, PRF mutant of Kunjin strain of WNV showed significant decrease compared to wild type virus infection in dissemination of the virus from the midgut through the haemocoel, and ultimately the capacity of infected mosquitoes to transmit virus. Thus our results demonstrate an important role for PRF in regulating expression of viral genes and consequently virus replication in avian and mosquito hosts.


title: Adecuación del tratamiento de la faringoamigdalitis aguda a la evidencia científica

text: Objetivos Analizar la idoneidad de los hábitos de prescripción de antibióticos en los pacientes pediátricos diagnosticados de faringoamigdalitis aguda métodos Estudio descriptivo de una serie de pacientes pediátricos diagnosticados de faringoamigdalitis aguda en los servicios de urgencias de 11 hospitales españoles. Estudio de idoneidad mediante la elaboración de estándares de referencia de uso apropiado y comparación de los datos del estudio descriptivo con tales estándares Resultados Se revisan 1.716 casos diagnosticados de faringoamigdalitis aguda. En el 80,9% de ellas se prescribieron antibióticos, en su mayoría siguiendo criterios empíricos. Los antibióticos más empleados fueron: amoxicilina (36,0 %), amoxicilina-ácido clavulánico (22,5 %), cefixima (6,6 %), azitromicina (5,8 %) y cefuroxima (5,2 %). El 39,5 % correspondían a menores de 3 años, de los que el 75,9% recibieron tratamiento empírico. El 22,8 % de las prescripciones se clasificaron como de primera elección, el 22,4% de uso alternativo y el 54,8 % inapropiadas Conclusiones En la mayoría de las faringoamigalitis se prescribió tratamiento antibiótico y en casi todos los casos se hizo de forma empírica. Además de la prescripción de antibióticos, en una proporción muy superior a la prevista de amigdalitis bacterianas, en un número no despreciable de casos se indicaron otros antibióticos diferentes a los considerados idóneos para esta enfermedad Objective To evaluate the appropriateness of antibiotic prescriptions in children with acute pharyngotonsillitis Methods A descriptive study was performed in a series of pediatric patients diagnosed with acute pharyngotonsillitis in the emergency rooms of 11 Spanish hospitals. The appropriateness of antibiotic prescriptions was assessed by comparing our clinical practice in the use of antibiotics for pharyngotonsillitis with consensus guidelines developed for this study Results We collected data from 1716 patients with acute pharyngotonsillitis. Antibiotics were prescribed in 80.9 %, mainly according to empirical criteria. The most commonly used antibiotics were amoxicillin (36 %), amoxicillinclavulanate (22.5 %), cefixime (6.6 %), azithromycin (5.8 %) and cefuroxime (5.2 %). A total of 39.5 % of the patients were aged less than 3 years, of which 75.9 % were treated empirically. Of the prescribed treatments, 22.8% were considered as the treatment of choice; 22.4 % as alternatives and 54.8 % as inappropriate Conclusions Antibiotic treatment was prescribed in most of the cases of pharyngotonsillitis and nearly always according to empirical criteria. The number of antibiotic prescriptions was far higher than the expected cases of bacterial pharyngotonsillitis and, in many cases, the antibiotic prescriptionswere inappropriate


title: Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway

text: Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, are enveloped RNA viruses that carry a large positive-sense single-stranded RNA genome and cause a variety of diseases in humans and domestic animals. Very little is known about the host pathways that regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense-mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs harboring aberrant features and targets them for degradation. Although CoV mRNAs are of cytoplasmic origin, the presence of several NMD-inducing features (including multiple ORFs with internal termination codons that create a long 3′ untranslated region) in CoV mRNAs led us to explore the interplay between the NMD pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in their degradation. Furthermore, CoV replication induced the inhibition of the NMD pathway, and N protein (a viral structural protein) had an NMD inhibitory function that protected viral mRNAs from rapid decay. Our data further suggest that the NMD pathway interferes with optimal viral replication by degrading viral mRNAs early in infection, before sufficient accumulation of N protein. Our study presents clear evidence for the biological importance of the NMD pathway in controlling the stability of mRNAs and the efficiency of replication of a cytoplasmic RNA virus.


title: New Epidemiological and Clinical Signatures of 18 Pathogens from Respiratory Tract Infections Based on a 5-Year Study

text: BACKGROUND: Respiratory tract infections (RTIs) are a heavy burden on society. However, due to the complex etiology of RTIs, the clinical diagnosis, treatment, and prevention of these infections remain challenging, especially in developing countries. METHODS: To determine the epidemiological and clinical characteristics of 18 respiratory pathogens, we analyzed 12,502 patients with acute respiratory infections (ARIs) by performing polymerase chain reaction (PCR) on patient pharyngeal swabs. RESULTS: Samples positive for at least 1 pathogen were obtained from 48.42% of the total patients. Of these pathogen-positive patients, 17.99% were infected with more than 1 pathogen. Of the 18 pathogens analyzed, four were detected with a positive detection rate (PDR) > 5%: influenza A virus (IAV) > respiratory syncytial virus (RSV) >Mycoplasma pneumoniae (MP) > human coronavirus (HCoV). The pathogens with the 4 highest co-infection rates (CIRs) were as follows: HCoV > human bocavirus (HBoV) > enterovirus (EV) > parainfluenza virus (PIV). The overall positive detection rate (PDR) varied significantly according to patient age, the season and year of detection, and the disease subgroup, but not according to patient sex. The individual PDRs of the pathogens followed 3 types of distributions for patient sex, 4 types of distributions for patient age, 4 types of seasonal distributions, 2 types of seasonal epidemic trends, 4 types of yearly epidemic trends, and different susceptibility distributions in the disease subgroups. Additionally, the overall CIR showed significantly different distributions according to patient sex, patient age, and the disease subgroup, whereas the CIRs of individual pathogens suggested significant preference characteristics. CONCLUSION: IAV remains the most common pathogen among the pathogens analyzed. More effort should be directed toward the prevention and control of pathogens that show a trend of increasing incidence such as HCoV, human adenovirus (ADV), and RSV. Although clinically distinguishing specific pathogens responsible for RTIs is difficult, the epidemiological and clinical characteristics of the various RTI-causing agents could provide clues for clinicians, thereby informing decisions regarding prevention and medication and guiding appropriate public health strategies.


title: Inhibition of measles virus and subacute sclerosing panencephalitis virus by RNA interference

text: Abstract Subacute sclerosing panencephalitis (SSPE) is a rare, but fatal outcome of measles virus (MeV) infection. SSPE develops after prolonged persistence of mutated MeV called SSPE virus. Although a combination therapy using interferon and inosiplex or ribavirin appears to prolong survival time to some extent, there is currently no effective treatment to completely cure SSPE and a new treatment strategy is greatly needed. In this study, we adopted RNA interference (RNAi) strategy and examined whether small interfering RNAs (siRNAs) can be used to inhibit replication of MeV and SSPE virus. We report here that siRNAs targeted against L mRNA of MeV, either synthetic siRNAs or those generated by pcPUR+U6i-based expression plasmids, effectively and specifically inhibited replication of both MeV and SSPE virus without exhibiting any cytotoxic effect. The L protein of MeV is a major component of RNA-dependent RNA polymerase that is essential for viral RNA replication, and yet it is least abundant among all the MeV proteins expressed. Therefore, mRNA encoding the L protein would be a good target for RNAi strategy. The present results imply the possibility that our siRNAs against MeV L mRNA are among the potential candidates to be used to treat patients with SSPE.


title: Teenage asthma after severe early childhood wheezing: An 11‐year prospective follow‐up

text: The role of factors related to early wheezing and their associations with subsequent development of asthma are controversial. We reevaluated 81 children who had been prospectively followed up since hospitalization for wheezing at less than 2 years of age. The baseline data on characteristics of the children, family‐related factors, and viral causes of wheezing were collected on entry into the study. At the median age of 12.3 years, current symptoms suggestive of asthma and allergy were recorded. As part of the clinical examination, an outdoor exercise challenge test and skin prick tests to common inhalant allergens were performed. Asthma, as indicated by current inhaled anti‐inflammatory medication or repeated wheezing and positive result in the challenge test, was present in 32 (40%) children, and 90% of them were sensitized to at least one allergen. Early asthma‐predictive factors were atopic dermatitis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.2–10.1) and the presence of specific IgE to inhalant allergens (OR, 11.3; 95% CI, 1.9–67.6). Respiratory syncytial virus (RSV) identification during wheezing in infancy was relatively rare (20%) among later asthmatics compared with other or no viral identification (52%) or rhinovirus identification (58%). Since the prevalence of childhood asthma in our area is 4.0–5.0%, we conclude that the increased risk of asthma persists until the teenage years after hospitalization for wheezing in infancy. The risk was about 5‐fold after respiratory syncytial virus‐induced wheezing, and more than 10‐fold after rhinovirus‐induced wheezing in the present study. Pediatr Pulmonol. © 2005 Wiley‐Liss, Inc.


title: COVID-19, an opportunity to reevaluate the correlation between long-term effects of anthropogenic pollutants on viral epidemic/pandemic events and prevalence

text: Occupational, residential, dietary and environmental exposures to mixtures of synthetic anthropogenic chemicals after World War II have a strong relationship with the increase of chronic diseases, health cost and environmental pollution. The link between environment and immunity is particularly intriguing as it is known that chemicals and drugs can cause immunotoxicity (e.g., allergies and autoimmune diseases). In this review, we emphasize the relationship between long-term exposure to xenobiotic mixtures and immune deficiency inherent to chronic diseases and epidemics/pandemics. We also address the immunotoxicologic risk of vulnerable groups, taking into account biochemical and biophysical properties of SARS-CoV-2 and its immunopathological implications. We particularly underline the common mechanisms by which xenobiotics and SARS-CoV-2 act at the cellular and molecular level. We discuss how long-term exposure to thousand chemicals in mixtures, mostly fossil fuel derivatives, exposure toparticle matters, metals, ultraviolet (UV)–B radiation, ionizing radiation and lifestyle contribute to immunodeficiency observed in the contemporary pandemic, such as COVID-19, and thus threaten global public health, human prosperity and achievements, and global economy. Finally, we propose metrics which are needed to address the diverse health effects of anthropogenic COVID-19 crisis at present and those required to prevent similar future pandemics.


title: Opportunistic intruders: how viruses orchestrate ER functions to infect cells

text: Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents.


title: Beliefs and Knowledge about Vaccination against AH1N1pdm09 Infection and Uptake Factors among Chinese Parents

text: Vaccination against AH1N1pdm09 infection (human swine infection, HSI) is an effective measure of preventing pandemic infection, especially for high-risk groups like children between the ages of 6 months and 6 years. This study used a cross-sectional correlation design and aimed to identify predicting factors of parental acceptance of the HSI vaccine (HSIV) and uptake of the vaccination by their preschool-aged children in Hong Kong. A total of 250 parents were recruited from four randomly selected kindergartens. A self-administered questionnaire based on the health belief framework was used for data collection. The results showed that a number of factors significantly affected the tendency toward new vaccination uptake; these factors included parental age, HSI vaccination history of the children in their family, preferable price of the vaccine, perceived severity, perceived benefits, perceived barriers, and motivating factors for taking new vaccines. Using these factors, a logistic regression model with a high Nagelkerke R(2) of 0.63 was generated to explain vaccination acceptance. A strong correlation between parental acceptance of new vaccinations and the motivating factors of vaccination uptake was found, which indicates the importance of involving parents in policy implementation for any new vaccination schemes. Overall, in order to fight against pandemics and enhance vaccination acceptance, it is essential for the government to understand the above factors determining parental acceptance of new vaccinations for their preschool-aged children.


title: El suplemento con altas dosis de vitamina D podría representar una alternativa promisoria para prevenir o tratar la infección por COVID-19

text: Resumen Si bien carecemos de suficiente evidencia que justifique suplementar con vitamina D en la prevención y/o tratamiento de la infección por COVID-19, a la fecha resulta cada vez más factible que esta hipótesis sea válida. Dos mecanismos básicos generales deberían ser considerados. Uno sería la acción anti-infecciosa e inmuno-moduladora que ejerce mejorando las barreras intercelulares por estímulo de la inmunidad innata, así también por modulación de la inmunidad adaptativa. También, la vitamina D reduce la producción de citoquinas inflamatorias como IL-2 e interferón gamma (INFγ). Más recientemente se han demostrado múltiples efectos pleiotrópicos sobre las acciones de vitamina D a nivel anti-inflamatorio e inmuno-modulador. Esto explica resultados positivos en estudios con influenza, coronavirus y otras infecciones respiratorias. Se ha descripto relación inversa entre niveles séricos de vitamina D y prevalencia de patología infecciosa respiratoria. De interés, otro abordaje mecanístico responde a considerar la inhibición del sistema renina-angiotensina-aldosterona, que se exacerba en la infección por COVID-19 debido a que el virus se une a la enzima ECA2, quedando disponible más angiotensina II para causar daño. La vitamina D inhibe mediadores del SRAA -presente en todas las células del organismo-, y por inhibir la actividad ECA y aumentar la ECA2, disminuye los niveles de angiotensina II. Presentamos estudios con propuestas de dosis recomendadas de vitamina D y aunque no quede concretada una única guía, los posibles beneficios son promisorios. Finalmente, el propósito de la presente revisión es compartir esta idea con profesionales de la salud para encender el debate y llamar a la reflexión crítica, de modo tal que se pueda contribuir con el emprendimiento de diseños clínicos adecuados para validar los beneficios de utilizar altas dosis de vitamina D en beneficio de la salud pública y sobre todo en tiempos de esta emergencia por COVID-19. Abstract Although we lack enough evidence to justify supplementing with vitamin D in the prevention and treatment of COVID-19 infection, it is increasingly feasible that this hypothesis is valid. Two general underlying mechanisms should be considered. One would be the anti-infectious and immunomodulatory action that it exerts by improving intercellular barriers by stimulating innate immunity, as well as by modulating adaptive immunity. Also, vitamin D reduces the production of inflammatory cytokines, such as IL-2 and interferon-gamma (INFγ). More recently, multiple pleiotropic effects have been demonstrated on the actions of vitamin D at the anti-inflammatory and immunomodulatory level with positive results in studies with influenza, coronavirus, and other respiratory infections. An inverse relationship between serum vitamin D levels and the prevalence of the respiratory infectious disease has been described. Of interest, another mechanistic approach responds to considering the inhibition of the renin-angiotensin-aldosterone system (RAAS), which is exacerbated in COVID-19 infection because the virus binds to the enzyme ACE2, making more angiotensin II available to cause damage. Vitamin D inhibits mediators of RAAS -present in all cells of the body- and by inhibiting ACE activity and increasing ACE2, it lowers angiotensin II levels. We present studies with proposals for recommended doses of vitamin D, and although a single guideline is not specified, the possible benefits are promising. Finally, the purpose of this review is to share this idea with health professionals to ignite the debate and call for critical reflection, so that it can contribute to the undertaking of more and better clinical designs to validate the benefits of using high doses of vitamin D for the benefit of public health and especially in times of crisis for COVID-19.


title: Narrative review of Middle East respiratory syndrome coronavirus (MERS-CoV) infection: updates and implications for practice

text: Human coronaviruses (HCoVs) comprise six subtypes of coronavirus that are associated with a number of respiratory diseases such as common cold, pneumonia, and bronchitis. Middle East respiratory syndrome coronavirus (MERS-CoV) is one of these six HCoV subtypes. HCoVs can result in life-threatening respiratory diseases, such as pneumonia and bronchiolitis, and may cause enteric and neurologic diseases, especially in immunocompromised patients. This narrative review aimed to enrich the knowledge of health care professional regarding MERS-CoV infection epidemiology, control, and management. This review discusses MERS-CoV prevalence, clinical manifestation, modes of transmission, control measures, and management, which we identified in a search of various databases, related journals, and the published literature. It has been shown that MERS-CoV infection is likely to be transmitted among countries. Therefore, countries with a high rate of MERS-CoV infection are urged to develop and implement guidelines to minimize the spread of infection. Countries must give careful consideration to raising public awareness in regions that are affected by MERS-CoV infection and the importance of reporting any disease signs and symptoms, to receive proper care.


title: Time Series Analysis and Forecast of the COVID-19 Pandemic in India using Genetic Programming

text: COVID-19 declared as a global pandemic by WHO, has emerged as the most aggressive disease, impacting more than 90% countries of the world. The virus started from a single human being in China, is now increasing globally at a rate of 3% to 5% daily and has become a never ending process. Some studies even predict that the virus will stay with us forever. India being the second most populous country of the world, is also not saved, and the virus is spreading as a community level transmitter. Therefore, it become really important to analyse the possible impact of COVID-19 in India and forecast how it will behave in the days to come. In present work, prediction models based on genetic programming (GP) have been developed for confirmed cases (CC) and death cases (DC) across three most affected states namely Maharashtra, Gujarat and Delhi as well as whole India. The proposed prediction models are presented using explicit formula, and impotence of prediction variables are studied. Here, statistical parameters and metrics have been used for evaluated and validate the evolved models. From the results, it has been found that the proposed GEP-based models use simple linkage functions and are highly reliable for time series prediction of COVID-19 cases in India.


Antibodies to SARS-like virus hint at repeated infections


title: Cough-generated aerosols of Pseudomonas aeruginosa and other Gram-negative bacteria from patients with cystic fibrosis

text: BACKGROUND: Pseudomonas aeruginosa is the most common bacterial pathogen in patients with cystic fibrosis (CF). Current infection control guidelines aim to prevent transmission via contact and respiratory droplet routes and do not consider the possibility of airborne transmission. It was hypothesised that subjects with CF produce viable respirable bacterial aerosols with coughing. METHODS: A cross-sectional study was undertaken of 15 children and 13 adults with CF, 26 chronically infected with P aeruginosa. A cough aerosol sampling system enabled fractioning of respiratory particles of different sizes and culture of viable Gram-negative non-fermentative bacteria. Cough aerosols were collected during 5 min of voluntary coughing and during a sputum induction procedure when tolerated. Standardised quantitative culture and genotyping techniques were used. RESULTS: P aeruginosa was isolated in cough aerosols of 25 subjects (89%), 22 of whom produced sputum samples. P aeruginosa from sputum and paired cough aerosols were indistinguishable by molecular typing. In four cases the same genotype was isolated from ambient room air. Approximately 70% of viable aerosols collected during voluntary coughing were of particles ⩽3.3 μm aerodynamic diameter. P aeruginosa, Burkholderia cenocepacia, Stenotrophomonas maltophilia and Achromobacter xylosoxidans were cultivated from respiratory particles in this size range. Positive room air samples were associated with high total counts in cough aerosols (p = 0.003). The magnitude of cough aerosols was associated with higher forced expiratory volume in 1 s (r = 0.45, p = 0.02) and higher quantitative sputum culture results (r = 0.58, p = 0.008). CONCLUSION: During coughing, patients with CF produce viable aerosols of P aeruginosa and other Gram-negative bacteria of respirable size range, suggesting the potential for airborne transmission.


title: Applying lessons from the Ebola vaccine experience for SARS-CoV-2 and other epidemic pathogens

text: The world is experiencing an unprecedented global pandemic of coronavirus disease 2019 (COVID-19) caused by a novel coronavirus, Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2). Development of new vaccines and therapeutics are important to achieve long-term prevention and control of the virus. Experience gained in the development of vaccines for Ebola virus disease provide important lessons in the regulatory, clinical, and manufacturing process that can be applied to SARS-CoV-2 and other epidemic pathogens. This report outlines the main lessons learned by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (MSD) during development of an Ebola Zaire vaccine (ERVEBO®) and looks ahead to critical lessons beyond vaccine development. It highlights focus areas for public-private partnership and regulatory harmonization that can be directly applied to current vaccine development efforts for SARS-CoV-2, while drawing attention to the need for parallel consideration of issues beyond development that are equally important to achieve global preparedness and response goals.


title: Host Transcriptional Response to Influenza and Other Acute Respiratory Viral Infections – A Prospective Cohort Study

text: To better understand the systemic response to naturally acquired acute respiratory viral infections, we prospectively enrolled 1610 healthy adults in 2009 and 2010. Of these, 142 subjects were followed for detailed evaluation of acute viral respiratory illness. We examined peripheral blood gene expression at 7 timepoints: enrollment, 5 illness visits and the end of each year of the study. 133 completed all study visits and yielded technically adequate peripheral blood microarray gene expression data. Seventy-three (55%) had an influenza virus infection, 64 influenza A and 9 influenza B. The remaining subjects had a rhinovirus infection (N = 32), other viral infections (N = 4), or no viral agent identified (N = 24). The results, which were replicated between two seasons, showed a dramatic upregulation of interferon pathway and innate immunity genes. This persisted for 2-4 days. The data show a recovery phase at days 4 and 6 with differentially expressed transcripts implicated in cell proliferation and repair. By day 21 the gene expression pattern was indistinguishable from baseline (enrollment). Influenza virus infection induced a higher magnitude and longer duration of the shared expression signature of illness compared to the other viral infections. Using lineage and activation state-specific transcripts to produce cell composition scores, patterns of B and T lymphocyte depressions accompanied by a major activation of NK cells were detected in the acute phase of illness. The data also demonstrate multiple dynamic gene modules that are reorganized and strengthened following infection. Finally, we examined pre- and post-infection anti-influenza antibody titers defining novel gene expression correlates.


title: Specific recombinant proteins of porcine epidemic diarrhea virus are immunogenic, revealing their potential use as diagnostic markers

text: Abstract Given the highly contagious and acute nature of porcine epidemic diarrhea (PED), especially in piglets, there is an urgent need for the development of rapid and sensitive diagnostic assays. The diagnostic potentials of specific porcine epidemic diarrhea virus (PEDV) accessory and nonstructural proteins, if any, have not yet been investigated. In order to determine and compare which of the viral proteins may be useful as diagnostic antigens, whole virus (WV) particles and a panel of structural and nonstructural PEDV proteins [spike subunit 1 (S1), the C-terminal part of ORF3 (ORF3C), envelope (E), nonstructural protein 1 (Nsp1), Nsp2, Ac (acidic domain of Nsp3), and ADRP (ADP-ribose-1-monophosphatase domain of Nsp3), expressed individually in bacterial and/or mammalian cells] were tested for reactivity with sera from PEDV-infected pigs by ELISA and/or western blot analysis. According to western blots, serum antibody interactions with the S1 protein were relatively more sensitive and specific than ORF3C, E and Ac. Furthermore, a total of 851 serum samples from diarrheal pigs of different ages were analyzed by ELISA, with most showing immune-reactivity towards the WV, S1, ORF3C, and E proteins. The earliest IgG antibody response was observed in the one-week-old piglets, with similar antibody ontogeny and patterns of seroconversion for S1, ORF3C, E, and WV antigens. In addition, the pattern of neutralizing antibody was more similar to that of IgA in weaning piglets after PEDV infection. Collectively, these data provide more reliable information on the host immune response to different viral proteins, which will be useful for development of novel serological assays and for design of vaccines that better stimulate protective immunity.


title: Health system collapse 45 days after the detection of COVID-19 in Ceará, Northeast Brazil: a preliminary analysis

text: INTRODUCTION: COVID-19 emerged in late 2019 and quickly became a serious public health problem worldwide. This study aim to describe the epidemiological course of cases and deaths due to COVID-19 and their impact on hospital bed occupancy rates in the first 45 days of the epidemic in the state of Ceará, Northeastern Brazil. METHODS: The study used an ecological design with data gathered from multiple government and health care sources. Data were analyzed using Epi Info software. RESULTS: The first cases were confirmed on March 15, 2020. After 45 days, 37,268 cases reported in 85.9% of Ceará’s municipalities, with 1,019 deaths. Laboratory test positivity reached 84.8% at the end of April, a period in which more than 700 daily tests were processed. The average age of cases was 67 (<1 - 101) years, most occurred in a hospital environment (91.9%), and 58% required hospitalization in an ICU bed. The average time between the onset of symptoms and death was 18 (1 - 56) days. Patients who died in the hospital had spent an average of six (0 - 40) days hospitalized. Across Ceará, the bed occupancy rate reached 71.3% in the wards and 80.5% in the ICU. CONCLUSIONS: The first 45 days of the COVID-19 epidemic in Ceará revealed a large number of cases and deaths, spreading initially among the population with a high socioeconomic status. Despite the efforts by the health services and social isolation measures the health system still collapsed.


title: Truncation of C-terminal 20 amino acids in PA-X contributes to adaptation of swine influenza virus in pigs

text: The PA-X protein is a fusion protein incorporating the N-terminal 191 amino acids of the PA protein with a short C-terminal sequence encoded by an overlapping ORF (X-ORF) in segment 3 that is accessed by + 1 ribosomal frameshifting, and this X-ORF exists in either full length or a truncated form (either 61-or 41-condons). Genetic evolution analysis indicates that all swine influenza viruses (SIVs) possessed full-length PA-X prior to 1985, but since then SIVs with truncated PA-X have gradually increased and become dominant, implying that truncation of this protein may contribute to the adaptation of influenza virus in pigs. To verify this hypothesis, we constructed PA-X extended viruses in the background of a “triple-reassortment” H1N2 SIV with truncated PA-X, and evaluated their biological characteristics in vitro and in vivo. Compared with full-length PA-X, SIV with truncated PA-X had increased viral replication in porcine cells and swine respiratory tissues, along with enhanced pathogenicity, replication and transmissibility in pigs. Furthermore, we found that truncation of PA-X improved the inhibition of IFN-I mRNA expression. Hereby, our results imply that truncation of PA-X may contribute to the adaptation of SIV in pigs.


title: The Art of War: battles between virus and host

text: As Sun Tzu wrote in The Art of War, “All warfare is based on deception”. He could have easily been describing the ancient battle between virus and host rather than on the lore of Chinese warfare. A virus must infect, replicate and spread for it to survive; the host attempting to thwart it at every step of the way. This ancient battle has been waged for millions of years and has spawned an innumerable number of viruses, each with their own unique ways of trying to outsmart the host. Some viruses encode proteins that directly inhibit/degrade/alter host pathways and some simply have evolved ways to hide from the hosts detection system. The host is not passive in this battle. It has evolved complex pathways and redundant mechanisms to respond to viral interlopers.


title: A novel synthesis and detection method for cap-associated adenosine modifications in mouse mRNA

text: A method is described for the detection of certain nucleotide modifications adjacent to the 5' 7-methyl guanosine cap of mRNAs from individual genes. The method quantitatively measures the relative abundance of 2'-O-methyl and N(6),2'-O-dimethyladenosine, two of the most common modifications. In order to identify and quantitatify the amounts of N(6),2'-O-dimethyladenosine, a novel method for the synthesis of modified adenosine phosphoramidites was developed. This method is a one step synthesis and the product can directly be used for the production of N(6),2'-O-dimethyladenosine containing RNA oligonucleotides. The nature of the cap-adjacent nucleotides were shown to be characteristic for mRNAs from individual genes transcribed in liver and testis.


title: Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19

text: Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.


Tocilizumab for refractory severe immune checkpoint inhibitor–associated myocarditis


title: Faster recovery and reduced paracetamol use – a meta-analysis of EPs 7630 in children with acute respiratory tract infections

text: OBJECTIVE: Fever is a very common adaptive immune response in acute respiratory tract disorders during infancy. Antipyretic / analgesic drugs such as paracetamol (acetaminophen) are widely used to improve the comfort of the child but may cause medically unneeded antipyresis and rare but potentially serious side effects. We assess whether treatment with Pelargonium sidoides extract EPs 7630 reduces the administration of paracetamol in children with acute tonsillopharyngitis (ATP) or acute bronchitis (AB). DESIGN: Meta-analysis of randomised, placebo-controlled clinical trials. METHODS: We searched clinical trial registries (ISRCTN, ClinicalTrials.gov) and medical literature (MEDLINE, EMBASE), for randomised, placebo-controlled trials investigating the administration of EPs 7630 to children with ATP or AB and reporting the co-administration of paracetamol. Based on the individual participant data of the eligible trials, study populations were characterized according to sex and age, and meta-analyses were performed for cumulative paracetamol use and ability to attend school at treatment end. RESULTS: Six trials including a total of 523 children aged 6–10 years (EPs 7630: 265; placebo: 258) and suffering from non-β-hemolytic streptococcal ATP (3 trials) or from AB (3 trials) were identified and eligible. Children received EPs 7630 or placebo for 6 (ATP) or 7 days (AB). Compared to placebo, EPs 7630 reduced the cumulative dose of paracetamol in 5 out of the 6 trials, by an average of 244 mg (Hedges’ g; − 0.28; 95% confidence interval: [− 0.53; − 0.02]; p < 0.03). At treatment end, 30.2% (EPs 7630) and 74.4% (placebo) of the children were still unable to attend school (risk ratio: 0.43; 95% confidence interval: [0.29; 0.65]; p < 0.001). CONCLUSIONS: In children aged 6–10 years with AB or ATP, EPs 7630 alleviated the symptom burden and accelerated recovery. Although EPs 7630 has no known antipyretic effect, concomitant use of paracetamol was reduced.


title: Recent Advances in Childhood Diarrhoeal Diseases

text: Over the past 20 years there have been many important advances in knowledge about diarrhoeal diseases of children. Of these, the development of oral rehydration therapy (ORT), has been outstanding. This is based on the observation that intestinal sodium transport is enhanced by glucose transport in the small intestine and that this sodium‐coupled mechanism for glucose and water transport remains intact in the enterotoxigenic diarrhoeas despite the net secretory effects of bacterial enterotoxins on the small intestinal epithelium. The World Health Organisation has adopted ORT and strongly promoted its application for treatment of diarrhoeal diseases, particularly in developing countries. This has resulted in a drop in diarrhoeal disease mortality and the application of this treatment has been described in an Editorial in the Lancet us“potentially the most important medical advance this century” [1].


title: Altering SARS Coronavirus Frameshift Efficiency Affects Genomic and Subgenomic RNA Production

text: In previous studies, differences in the amount of genomic and subgenomic RNA produced by coronaviruses with mutations in the programmed ribosomal frameshift signal of ORF1a/b were observed. It was not clear if these differences were due to changes in genomic sequence, the protein sequence or the frequency of frameshifting. Here, viruses with synonymous codon changes are shown to produce different ratios of genomic and subgenomic RNA. These findings demonstrate that the protein sequence is not the primary cause of altered genomic and subgenomic RNA production. The synonymous codon changes affect both the structure of the frameshift signal and frameshifting efficiency. Small differences in frameshifting efficiency result in dramatic differences in genomic RNA production and TCID(50) suggesting that the frameshifting frequency must stay above a certain threshold for optimal virus production. The data suggest that either the RNA sequence or the ratio of viral proteins resulting from different levels of frameshifting affects viral replication.


title: Immunization with Live Human Rhinovirus (HRV) 16 Induces Protection in Cotton Rats against HRV14 Infection

text: Human rhinoviruses (HRVs) are the main cause of cold-like illnesses, and currently no vaccine or antiviral therapies against HRVs are available to prevent or mitigate HRV infection. There are more than 150 antigenically heterogeneous HRV serotypes, with ∼90 HRVs belonging to major group species A and B. Development of small animal models that are susceptible to infection with major group HRVs would be beneficial for vaccine research. Previously, we showed that the cotton rat (Sigmodon hispidus) is semi-permissive to HRV16 (major group, species HRV-A virus) infection, replicating in the upper and lower respiratory tracts with measurable pathology, mucus production, and expression of inflammatory mediators. Herein, we report that intranasal infection of cotton rats with HRV14 (major group, species HRV-B virus) results in isolation of infectious virus from the nose and lung. Similar to HRV16, intramuscular immunization with live HRV14 induces homologous protection that correlated with high levels of serum neutralizing antibodies. Vaccination and challenge experiments with HRV14 and HRV16 to evaluate the development of cross-protective immunity demonstrate that intramuscular immunization with live HRV16 significantly protects animals against HRV14 challenge. Determination of the immunological mechanisms involved in heterologous protection and further characterization of infection with other major HRV serotypes in the cotton rat could enhance the robustness of the model to define heterotypic relationships between this diverse group of viruses and thereby increase its potential for development of a multi-serotype HRV vaccine.


title: Inhibition of cell proliferation by SARS-CoV infection in Vero E6 cells

text: Severe acute respiratory syndrome (SARS) is caused by SARS-coronavirus (SARS-CoV). Infection of Vero E6 cells with SARS-CoV inhibits cell proliferation. Our previous study indicated that Akt, which is poorly phosphorylated in confluent cultures of Vero E6 cells, is phosphorylated and then dephosphorylated upon infection by SARS-CoV. In the present study, we showed that a serine residue of Akt was phosphorylated in Vero E6 cells in subconfluent culture and that Akt was dephosphorylated rapidly after SARS-CoV infection without up-regulation of its phosphorylation. Phosphorylation of glycogen synthase kinase-3β, which is one of the downstream targets of Akt, was prevented in SARS-CoV-infected cells. However, treatment with glycogen synthase kinase-3β small interfering RNA indicated that the glycogen synthase kinase-3β signaling pathway was not related to inhibition of cell proliferation. Treatment of Vero E6 cells with the phosphatidylinositol 3′-kinase/Akt inhibitor, LY294002, which induces dephosphorylation of Akt, inhibited cell proliferation. As shown in our previous studies, apoptosis occurred in virus-infected cells within 18 h postinfection. Cellular mRNA transcription, which was reported to be up-regulated in SARS-CoV-infected Caco-2 cells, was not up-regulated in virus-infected Vero E6 cells, partially as a result of apoptosis. These results suggested that inhibition of cell proliferation is regulated by both the phosphatidylinositol 3′-kinase/Akt signaling pathway and by apoptosis in SARS-CoV-infected Vero E6 cells. This is the first study to analyze SARS-CoV-induced cell growth inhibition.


title: Dentists’ Awareness, Perception, and Attitude Regarding COVID-19 and Infection Control: Cross-Sectional Study Among Jordanian Dentists

text: BACKGROUND: Despite the availability of prevention guidelines and recommendations on infection control, many dental practices lack the minimum requirements for infection control. OBJECTIVE: This study aimed to assess the level of awareness, perception, and attitude regarding the coronavirus disease (COVID-19) and infection control among Jordanian dentists. METHODS: The study population consisted of dentists who worked in private clinics, hospitals, and health centers in Jordan. An online questionnaire was sent to a sample of Jordanian dentists in March 2020. The questionnaire was comprised of a series of questions about dentists’ demographic characteristics; their awareness of the incubation period, the symptoms of the disease, mode of transmission of COVID-19 and infection control measures for preventing COVID-19; and their attitude toward treating patients with COVID-19. RESULTS: This study included a total of 368 dentists aged 22-73 years (mean 32.9 years, SD 10.6 years). A total of 112 (30.4%) dentists had completed a master or residency program in dentistry, 195 (53.0%) had received training in infection control in dentistry, and 28 (7.6%) had attended training or lectures regarding COVID-19. A total of 133 (36.1%) dentists reported that the incubation period is 1-14 days. The majority of dentists were aware of COVID-19 symptoms and ways of identifying patients at risk of having COVID-19, were able to correctly report known modes of transmission, and were aware of measures for preventing COVID-19 transmission in dental clinics. A total of 275 (74.7%) believed that it was necessary to ask patients to sit far from each other, wear masks while in the waiting room, and wash hands before getting in the dental chair to decrease disease transmission. CONCLUSIONS: Jordanian dentists were aware of COVID-19 symptoms, mode of transmission, and infection controls and measures in dental clinics. However, dentists had limited comprehension of the extra precautionary measures that protect the dental staff and other patients from COVID-19. National and international guidelines should be sent by the regional and national dental associations to all registered dentists during a crisis, including the COVID-19 pandemic, to make sure that dentists are well informed and aware of best practices and recommended disease management approaches.


title: MicroRNA-221-5p Inhibits Porcine Epidemic Diarrhea Virus Replication by Targeting Genomic Viral RNA and Activating the NF-κB Pathway

text: MicroRNAs (miRNAs) are a class of noncoding RNAs involved in posttranscriptional regulation of gene expression and many critical roles in numerous biological processes. Porcine epidemic diarrhea virus (PEDV), the etiological agent of porcine epidemic diarrhea, causes substantial economic loss in the swine industry worldwide. Previous studies reported miRNA involvement in viral infection; however, their role in regulating PEDV infection remains unknown. In this study, we investigated the regulatory relationship between miRNA-221-5p and PEDV infection, finding that miR-221-5p overexpression inhibited PEDV replication in a dose-dependent manner, and that silencing endogenous miR-221-5p enhanced viral replication. Our results showed that miR-221-5p directly targets the 3′ untranslated region (UTR) of PEDV genomic RNA to inhibit PEDV replication, and that miR-221-5p overexpression activates nuclear factor (NF)-κB signaling via p65 nuclear translocation, thereby upregulating interferon (IFN)-β, IFN-stimulated gene 15, and MX1 expression during CH/HBTS/2017 infection. We subsequently identified NF-κB-inhibitor α and suppressor of cytokine signaling 1, negative regulators of the NF-κB pathway, as miR-221-5p targets. These results demonstrated the ability of miR-221-5p to inhibit PEDV replication by targeting the 3’ UTR of the viral genome and activating the NF-κB-signaling pathway. Our findings will aid the development of preventive and therapeutic strategies for PEDV infection.


title: Evolutionary relationships and sequence‐structure determinants in human SARS coronavirus‐2 spike proteins for host receptor recognition

text: Coronavirus disease 2019 (COVID‐19) is a pandemic infectious disease caused by novel Severe Acute Respiratory Syndrome coronavirus‐2 (SARS CoV‐2). The SARS CoV‐2 is transmitted more rapidly and readily than SARS CoV. Both, SARS CoV and SARS CoV‐2 via their glycosylated spike proteins recognize the human angiotensin converting enzyme‐2 (ACE‐2) receptor. We generated multiple sequence alignments and phylogenetic trees for representative spike proteins of SARS CoV and SARS CoV‐2 from various host sources in order to analyze the specificity in SARS CoV‐2 spike proteins required for causing infection in humans. Our results show that among the genomes analysed, two sequence regions in the N‐terminal domain (NTD); "MESEFR" and "SYLTPG" are specific to human SARS CoV‐2. In the receptor binding domain (RBD), two sequence regions; "VGGNY" and "EIYQAGSTPCNGV" and a disulfide bridge connecting 480C and 488C in the extended loop are structural determinants for the recognition of human ACE‐2 receptor. The complete genome analysis of representative SARS CoVs from bat, civet, human host sources and human SARS CoV‐2 identified the bat genome (GenBank code: MN996532.1) as closest to the recent novel human SARS CoV‐2 genomes. The bat SARS CoV genomes (GenBank codes: MG772933 and MG772934) are evolutionary intermediates in the mutagenesis progression towards becoming human SARS CoV‐2. This article is protected by copyright. All rights reserved.


title: Late‐onset severe pneumonia after allogeneic hematopoietic stem cell transplantation: prognostic factors and treatments

text: BACKGROUND: In this study, we aimed to evaluate the prognostic factors associated with and treatments for late‐onset severe pneumonia (LOSP) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo‐HSCT). METHODS: Fifty consecutive patients who underwent non‐T‐cell‐depleted allo‐HSCT at the Peking University Institute of Hematology and met the criterion of LOSP after allo‐HSCT were enrolled. RESULTS: The median time from allo‐HSCT to the occurrence of LOSP was 231 (90–1487) days. Twenty‐eight patients harbored 1 or more pathogens (infectious LOSP, I‐LOSP), whereas 22 did not harbor any pathogens (non‐infectious LOSP, NI‐LOSP). The 100‐day survival rate of LOSP patients was 31.1%. Patients smoking before allo‐HSCT (0% vs. 35.4%, P = 0.002) and male gender (20.0% vs. 61.9%, P = 0.026) had lower 100‐day survival rate. Patients with a lower bronchoalveolar lavage fluid (BALF) neutrophil percentage had higher 100‐day survival rate relative to those with higher BALF neutrophil percentage (45.5% vs. 16.7%, P = 0.012). The 100‐day survival rate of patients with I‐LOSP was lower than that of patients with NI‐LOSP (19.1% vs. 46.9%, P = 0.043). Patients given late (≥1 week after LOSP diagnosis) and low‐dose methylprednisolone (MP) therapy (≤2 mg/kg/day) had the best 100‐day survival rate. In the multivariate analysis, nonsmoking before allo‐HSCT and late and low‐dose MP therapy were significantly associated with a better survival after LOSP. CONCLUSION: LOSP is a severe complication after allo‐HSCT. The correct timing and corticosteroid dosage in the context of broad‐spectrum antimicrobial therapy might further improve the outcomes of patients with LOSP.


title: Ocular manifestations and clinical characteristics of 535 cases of COVID‐19 in Wuhan, China: a cross‐sectional study

text: PURPOSE: To investigate the ocular manifestations and clinical characteristics of COVID‐19 patients caused by SARS‐CoV‐2 in Wuhan, China. METHODS: A total of 535 COVID‐19 patients were recruited at Mobile Cabin Hospital and Tongji Hospital. Information on demographic characteristics, exposure history, ocular symptoms, eye drop medication, eye protections, chronic eye diseases, systemic concomitant symptoms, radiologic findings and SARS‐CoV‐2 detection in nasopharyngeal swabs by real‐time PCR was collected from questionnaires and electronic medical records. RESULTS: Of 535 patients, 27 patients (5.0%) presented with conjunctival congestion and 4 patients had conjunctival congestion as the initial symptom. The average duration of conjunctival congestion was 5.9 ± 4.5 days (mean [SD]). The other ocular symptoms, including increased conjunctival secretion, ocular pain, photophobia, dry eye and tearing, were also found in patients with conjunctival congestion. Notably, hand–eye contact was independently correlated with conjunctival congestion in COVID‐19 patients. We also found that some COVID‐19 patients had chronic eye diseases, including conjunctivitis (33, 6.2%), xerophthalmia (24, 4.5%) and keratitis (14, 2.6%). Similar to the published studies, the most common clinical symptoms were fever, cough and fatigue. A total of 343 patients (64.1%) had positive SARS‐CoV‐2 detection in nasopharyngeal swabs. CONCLUSIONS: Conjunctival congestion is one of the COVID‐19‐related ocular symptoms, which could occur as the initial symptoms. Frequent hand–eye contact may be the risk factor for conjunctival congestion in COVID‐19 patients. Screening of patients with conjunctival congestion by ophthalmologists is advocated during the outbreak of COVID‐19. It is essential to provide eye‐care equipment and strengthen education on eye protection.


Cardiac troponin I in patients with coronavirus disease 2019 (COVID-19): Evidence from a meta-analysis()


Material methods for a rapid‐response anthropology


Held in conjunction with the 60th Annual Meeting of the Society for Birth Defects Research and Prevention and the 33rd Annual Education Meeting for the Organization of Teratology Information Specialists, Charleston, South Carolina, June 27–July 1, 2020 Meeting Cancelled due to COVID-19 Global Pandemic


title: Microwave-Generated Steam Decontamination of N95 Respirators Utilizing Universally Accessible Materials

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect health care providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work, we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1,100-W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log(10) plaque-forming unit (PFU) (99.9999%) and a minimum 5-log(10) PFU (99.999%) reduction after a single 3-min microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.


title: SARS‐CoV‐2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein

text: To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS‐CoV‐2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS‐CoV‐2 was more similar to the bats' betacoronavirus isolates: HKU5‐related from Pipistrellus abramus and HKU4‐related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS‐CoV‐2, responsible for the current outbreak of COVID‐19, could also come from yak as an intermediate host.


title: Disease control in a food chain model supplying alternative food

text: Abstract Necessity to find a non-chemical method of disease control is being increasingly felt due to its eco-friendly nature. In this paper the role of alternative food as a disease controller in a disease induced predator–prey system is studied. Stability criteria and the persistence conditions for the system are derived. Bifurcation analysis is done with respect to rate of infection. The main goal of this study is to show the non-trivial consequences of providing alternative food in a disease induced predator–prey system. Numerical simulation results illustrate that there exists a critical infection rate above which disease free system cannot be reached in absence of alternative food whereas supply of suitable alternative food makes the system disease free up to certain infection level. We have computed the disease free regions in various parametric planes. This study is aimed to introduce a new non-chemical method for controlling disease in a predator–prey system.


Human Bocavirus 2 in Children, South Korea


title: siRNA targeting the Leader sequence of SARS-CoV inhibits virus replication

text: SARS-CoV (the SARS-Associated Coronavirus) was reported as a novel virus member in the coronavirus family, which was the cause of severe acute respiratory syndrome. Coronavirus replication occurs through a unique mechanism employing Leader sequence in the transcripts when initiating transcription from the genome. Therefore, we cloned the Leader sequence from SARS-CoV(BJ01), which is identical to that identified from SARS-CoV(HKU-39849), and constructed specific siRNA targeting the Leader sequence. Using EGFP and RFP reporter genes fused with the cloned SARS-CoV Leader sequence, we demonstrated that the siRNA targeting the Leader sequence decreased the mRNA abundance and protein expression levels of the reporter genes in 293T cells. By stably expressing the siRNA in Vero E6 cells, we provided data that the siRNA could effectively and specifically decrease the mRNA abundance of SARS-CoV genes as analyzed by RT-PCR and Northern blot. Our data indicated that the siRNA targeting the Leader sequence inhibited the replication of SARS-CoV in Vero E6 cells by silencing gene expression. We further demonstrated, via transient transfection experiments, that the siRNA targeting the Leader sequence had a much stronger inhibitory effect on SARS-CoV replication than the siRNAs targeting the Spike gene or the antisense oligodeoxynucleotides did. This report provides evidence that targeting Leader sequence using siRNA could be a powerful tool in inhibiting SARS-CoV replication.


title: Structure, properties, and biological relevance of the DNA and RNA G-quadruplexes: Overview 50 years after their discovery

text: G-quadruplexes (G4s), which are known to have important roles in regulation of key biological processes in both normal and pathological cells, are the most actively studied non-canonical structures of nucleic acids. In this review, we summarize the results of studies published in recent years that change significantly scientific views on various aspects of our understanding of quadruplexes. Modern notions on the polymorphism of DNA quadruplexes, on factors affecting thermodynamics and kinetics of G4 folding–unfolding, on structural organization of multiquadruplex systems, and on conformational features of RNA G4s and hybrid DNA–RNA G4s are discussed. Here we report the data on location of G4 sequence motifs in the genomes of eukaryotes, bacteria, and viruses, characterize G4-specific small-molecule ligands and proteins, as well as the mechanisms of their interactions with quadruplexes. New information on the structure and stability of G4s in telomeric DNA and oncogene promoters is discussed as well as proof being provided on the occurrence of G-quadruplexes in cells. Prominence is given to novel experimental techniques (single molecule manipulations, optical and magnetic tweezers, original chemical approaches, G4 detection in situ, in-cell NMR spectroscopy) that facilitate breakthroughs in the investigation of the structure and functions of G-quadruplexes.


An international physical activity and public health research agenda to inform COVID-19 policies and practices


title: Exit and Entry Screening Practices for Infectious Diseases among Travelers at Points of Entry: Looking for Evidence on Public Health Impact

text: A scoping search and a systematic literature review were conducted to give an insight on entry and exit screening referring to travelers at points of entry, by analyzing published evidence on practices, guidelines, and experiences in the past 15 years worldwide. Grey literature, PubMed. and Scopus were searched using specific terms. Most of the available data identified through the systematic literature review concerned entry screening measures at airports. Little evidence is available about entry and exit screening measure implementation and effectiveness at ports and ground crossings. Exit screening was part of the World Health Organisation’s (WHO) temporary recommendations for implementation in certain points of entry, for specific time periods. Exit screening measures for Ebola Virus Disease (EVD) in the three most affected West African countries did not identify any cases and showed zero sensitivity and very low specificity. The percentages of confirmed cases identified out of the total numbers of travelers that passed through entry screening measures in various countries worldwide for Influenza Pandemic (H1N1) and EVD in West Africa were zero or extremely low. Entry screening measures for Severe Acute Respiratory Syndrome (SARS) did not detect any confirmed SARS cases in Australia, Canada, and Singapore. Despite the ineffectiveness of entry and exit screening measures, authors reported several important concomitant positive effects that their impact is difficult to assess, including discouraging travel of ill persons, raising awareness, and educating the traveling public and maintaining operation of flights from/to the affected areas. Exit screening measures in affected areas are important and should be applied jointly with other measures including information strategies, epidemiological investigation, contact tracing, vaccination, and quarantine to achieve a comprehensive outbreak management response. Based on review results, an algorithm about decision-making for entry/exit screening was developed.


title: The process by which perceived autonomy support predicts motivation, intention, and behavior for seasonal influenza prevention in Hong Kong older adults

text: BACKGROUND: This study examined the effectiveness of a theoretical framework that integrates self-determination theory (SDT) and the theory of planned behavior (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong Kong older adults. METHODS: Data were collected at two time points in the winter in Hong Kong, during which influenza is most prevalent. At Time 1, older adults (N = 141) completed self-report measures of SDT (perceived autonomy support from senior center staff, autonomous motivation for influenza prevention) and TPB (attitude, subjective norm, perceived behavioral control, and intention for influenza prevention) constructs with respect to facemask used to prevent infection. Two weeks later, at Time 2, participants’ acceptance of a facemask to prevent influenza in the presence of an experimenter with flu-like symptoms was recorded. RESULTS: Path analysis found that perceived autonomy support of senior center staff was positively and significantly linked to autonomous motivation for facemask use, which, in turn, was positively related to intentions to wear facemasks through the mediation of attitude, subjective norm, and perceived behavioral control. However, the effect of intention on facemask use was not significant. CONCLUSIONS: Results generally support the proposed framework and the findings of previous studies with respect to intention, but the non-significant intention-behavior relationship may warrant future research to examine the reasons for older adults not to wear facemasks to prevent seasonal influenza despite having positive intentions to do so.


title: Transmissible Gastroenteritis Virus Papain-Like Protease 1 Antagonizes Production of Interferon-β through Its Deubiquitinase Activity

text: Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2(pro), which may antagonize host innate immunity. However, very little is known about whether TGEV PL1 can antagonize host innate immune response. Here, we presented evidence that TGEV PL1 encoded by the replicase gene could suppress the IFN-β expression and inhibit the nuclear translocation of interferon regulatory factor 3 (IRF3). The ability to antagonize IFN-β production was dependent on the intact catalytic activity of PL1. Furthermore, TGEV PL1 exerted deubiquitinase (DUB) activity which strongly inhibited the retinoic acid-induced gene I- (RIG-1-) and stimulator of interferon gene- (STING-) dependent IFN expression. Our data collectively suggest that TGEV PL1 can inhibit the IFN-β expression and interfere with RIG-1- and STING-mediated signaling through a viral DUB activity. Our study has yielded strong evidence for the TGEV PL1 mechanisms that counteract the host innate immunity.


docid: wbfnhedy

title: Transient hyperglycosylation of rhodopsin with galactose

text: Abstract Rhodopsin's oligosaccharide chains contain predominantly two types of sugar residues: mannose and N-acetylglucosamine. In the present work, bovine and rat rhodopsin were analysed biochemically for the presence of a third sugar, galactose. Treatment of bovine rod outer segments (ROS) with galactose oxidase followed by reduction with tritium-labeled sodium borohydride revealed the presence of existing molecules of galactose on rhodopsin. Rats injected intravitreally with [3H]galactose and [14C]leucine and maintained in darkness were killed 1 hr, 6 hr, 1, 3, or 5 days following the injection. Retinas were collected for subcellular fractionation and rhodopsin from each of the fractions was purified by ConA sepharose chromatography and SDS-PAGE. During the first 6 hr, galactose selectively labeled rhodopsin in the Golgi-enriched fraction resulting in increased [3H] [14C] ratios in both Golgi and ROS. The data suggested that trimming was occurring at the transition from Golgi to ROS. Furthermore, a decrease in isotope ratio in the ROS between 6 hr and 1 day suggested further trimming of rhodopsin after membrane assembly in the ROS. Additional in vivo experiments demonstrated existing molecules of galactose on rhodopsin's oligosaccharide chain using lectin affinity chromatography. Rats injected intravitreally with [35S]methionine were dark-adapted for 2 hr. Following subcellular fractionation of retinas, ConA purified rhodopsin from ROS was applied to one of two additional lectin columns: Ricinus communis agglutinin (RCA) or Griffonia simplicifolia I (GSA). Eight to nine per cent of the labeled rhodopsin was bound to and eluted from RCA, whereas none bound to GSA, indicating the presence of a β-galactoside. The RCA agarose eluted protein co-electrophoresed with a rhodopsin standard and was light sensitive. Galactose was shown to be the terminal sugar on this subset of rhodopsin and was not capped by neuraminic acid. Binding of rhodopsin's oligosaccharide to RCA was abolished by pre-treatment with β-galactosidase. Decreased binding of rhodopsin to RCA was observed following intravitreal injection of castanospermine but not swainsonine. Of those two inhibitors of glycoprotein trimming, only castanospermine would be expected to prevent the addition of galactose to the oligosaccharide. The association of galactose with rat rhodopsin appeared to be a transient one. At 2 hr, 8–9% of rhodopsin contained galactose, at 6 hr only 2·2% had galactose and by 24 hr less than 1% did. The galactose was trimmed from rhodopsin's oligosaccharide presumably after its role was complete. Separation of rhodopsin of the plasma membranes from rhodopsin of discs indicated that 75% of the galactose-containing rhodopsin was in the plasma membrane and only 25% was in the discs. These findings suggested a possible role for galactose in new disc formation with subsequent removal after the discs are sealed.


title: Viral Interplay with the Host Sumoylation System

text: Viruses have evolved elaborate means to regulate diverse cellular pathways in order to create a cellular environment that facilitates viral survival and reproduction. This includes enhancing viral macromolecular synthesis and assembly, as well as preventing antiviral responses, including intrinsic, innate, and adaptive immunity. There are numerous mechanisms by which viruses mediate their effects on the host cell, and this includes targeting various cellular post-translational modification systems, including sumoylation. The wide-ranging impact of sumoylation on cellular processes such as transcriptional regulation, apoptosis, stress response, and cell cycle control makes it an attractive target for viral dysregulation. To date, proteins from both RNA and DNA virus families have been shown to be modified by SUMO conjugation, and this modification appears critical for viral protein function. More interestingly, members of the several viral families have been shown to modulate sumoylation, including papillomaviruses, adenoviruses, herpesviruses, orthomyxoviruses, filoviruses, and picornaviruses. This chapter will focus on mechanisms by which sumoylation both impacts human viruses and is used by viruses to promote viral infection and disease.


title: Respiratory Tract Infections Due to Human Metapneumovirus in Immunocompromised Children

text: BACKGROUND: The clinical presentation and management of human metapneumovirus (hMPV) infections in immunocompromised children is not well understood. METHODS: We performed a retrospective evaluation of pediatric patients with laboratory-confirmed hMPV infections and underlying hematologic malignancy, solid tumors, solid organ transplant, rheumatologic disease, and/or receipt of chronic immunosuppressants. Data were analyzed using t tests and Fisher's exact tests. RESULTS: Overall, 55 patients (median age: 5 years; range: 5 months–19 years) with hMPV infection documented between 2006 and 2010 were identified, including 24 (44%) with hematologic malignancy, 9 (16%) undergoing hematopoietic stem cell transplant, 9 (16%) with solid tumors, and 8 (15%) with solid organ transplants. Three (5%) presented with fever alone, 35 (64%) presented with upper respiratory tract infections, and 16 (29%) presented with lower respiratory tract infections (LRTI). Twelve (23%) patients required intensive care unit admission and/or supplemental oxygen ≥28% FiO(2). Those with severe disease were more likely to be neutropenic (P = .02), but otherwise did not differ by age (P = .27), hematopoietic stem cell transplant recipient status (P = .19), or presence of lymphopenia (P = .09). Nine (16%) patients received treatment with ribavirin, intravenous immunoglobulin, or both. Three children (5%) died of hMPV pneumonia. CONCLUSIONS: Immunocompromised pediatric patients with hMPV infection have high rates of LRTI and mortality. The benefits of treatment with ribavirin and intravenous immunoglobulin in this patient population require further evaluation.