title: Influence of maternal asthma on the cause and severity of infant acute respiratory tract infections

text: Background Respiratory syncytial virus (RSV) and rhinovirus infections are the most common significant infant respiratory tract illnesses and are associated with increased but differential risks of childhood asthma. Objective We sought to determine whether maternal asthma is associated with higher odds of infant respiratory tract infection with rhinovirus versus RSV and increased infection severity. Methods Mother-infant dyads were enrolled from 2004-2008 during an infant respiratory tract infection (104 with rhinovirus and 279 with RSV). Mothers were classified into mutually exclusive groups (atopic asthma, nonatopic asthma, and no asthma). We determined viral cause using PCR and the severity of the infant’s respiratory tract infection using the bronchiolitis severity score. Adjusted relative odds of maternal asthma with viral cause were calculated by using logistic regression. Proportional odds models assessed the association of maternal asthma and infant infection severity. Results Infants with a mother with atopic asthma compared with infants whose mothers did not have asthma were more likely to have rhinovirus versus RSV infection (adjusted odds ratio, 2.42; 95% CI, 1.19-4.90). Similarly, among infants with rhinovirus, having a mother with atopic asthma was associated with increased infection severity (adjusted odds ratio, 3.10; 95% CI, 1.21-7.98). This relationship was not seen among infants with RSV. Conclusions Clinically significant rhinovirus infection during infancy was more strongly associated with having a mother with atopic asthma than clinically significant RSV infection. Having a mother with atopic asthma was associated with increased severity of infant rhinovirus but not RSV infections. Infants with rhinovirus were more likely to have a familial atopic predisposition, which might partly explain the subsequent increased asthma risk.


Pandemic Response and International Health Regulations


title: A rapid point of care immunoswab assay for SARS-CoV detection

text: The emergence of severe acute respiratory syndrome (SARS) resulted in several outbreaks worldwide. Early tests for diagnosis were not always conclusive in identifying a SARS suspected patient. Nucleocapsid protein (NP) is the most predominant virus derived structural protein which is shed in high amounts in serum and nasopharyngeal aspirate during the first week of infection. As part of such efforts, a simple, easy to use immunoswab method was developed by generating a panel of monoclonal antibodies (MAbs), Bispecific MAbs and chicken polyclonal IgY antibody against the SARS-CoV nucleocapsid protein (NP). Employing the MAb-based immunoswab, an NP concentration of 200 pg/mL in saline and pig nasopharyngeal aspirate, and 500 pg/mL in rabbit serum were detected. BsMAb-based immunoswabs detected an NP concentration of 20 pg/mL in saline, 500 pg/mL in rabbit serum and 20–200 pg/mL in pig nasopharyngeal aspirate. Polyclonal IgY-based immunoswabs detected an NP concentration of 10 pg/mL in pig nasopharyngeal aspirate providing the most sensitive SARS point of care assay. Results show that the robust immunoswab method of detecting SARS-CoV NP antigen can be developed into an easy and effective way of identifying SARS suspected individuals during a future SARS epidemic, thereby reducing and containing the transmission. The key feature of this simple immunoswab diagnostic assay is its ability to detect the presence of the SARS-CoV antigen within 45–60 min with the availability of the body fluid samples.


title: Reporting effectiveness of an extract of three traditional Cretan herbs on upper respiratory tract infection: Results from a double-blind randomized controlled trial

text: Abstract Ethnopharmacological relevance Observations from the island of Crete, Greece suggest that infusions of traditional Cretan aromatic plants, well known for their ethnopharmacological use in Eastern Mediterranean region and Near East, could be effective in the prevention and treatment of upper respiratory tract infections, including viral-induced infections. The aim of this study was to report the effectiveness of an essential-oil extract of three Cretan aromatic plants in the treatment of cases with an upper respiratory tract infection. Materials and methods A double blind randomized controlled trial was implemented between October 2013 and February 2014. An essential-oil extract of Cretan aromatic plants in olive oil (total volume of 15ml of essential oil per litre of olive oil) was administered as 0.5ml soft gel capsules, twice a day, for 7 days. Placebo treatment was 0.5ml olive oil in soft gel capsules. Eligible patients were those presenting for clinical examination in the selected setting with signs and symptoms of upper respiratory tract infection that had begun within the previous 24hours. Real-Time Polymerase Chain Reaction (PCR) was used for the detection of respiratory viruses. The primary outcome was the severity and duration of symptoms of upper respiratory tract infection, assessed using the Wisconsin Upper Respiratory System Survey (WURSS-21) questionnaire. A secondary outcome of interest was the change in C-reactive protein (CRP) status. Results One hundred and five patients completed the study: 51 in the placebo group, and 54 in the intervention (treated) group. Baseline characteristics were similar in the two groups. No statistically significant differences were found in symptom duration or severity between the two groups, although small and clinically favorable effects were observed. When the analysis was restricted to subjects with a laboratory-documented viral infection, the percentage of patients with cessation of symptoms after 6 days of treatment was 91% in the intervention group and 70% in the control group (p=0.089). At baseline, one third of the patients in each group had elevated CRP levels. At follow-up, the respective proportions were 0% in the intervention group and 15% in the placebo group (p=0.121). The data were also in a favorable direction when 50% and 80% symptom reduction points were considered for specific virus types. Conclusions Compared with placebo the essential-oil extract of three Cretan aromatic plants provided no detectable statistically significant benefit or harm in the patients with upper respiratory illness, although descriptive differences were identified in favorable direction mainly in the virus-positive population.


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title: Natural Killer Cell Sensing of Infected Cells Compensates for MyD88 Deficiency but Not IFN-I Activity in Resistance to Mouse Cytomegalovirus

text: In mice, plasmacytoid dendritic cells (pDC) and natural killer (NK) cells both contribute to resistance to systemic infections with herpes viruses including mouse Cytomegalovirus (MCMV). pDCs are the major source of type I IFN (IFN-I) during MCMV infection. This response requires pDC-intrinsic MyD88-dependent signaling by Toll-Like Receptors 7 and 9. Provided that they express appropriate recognition receptors such as Ly49H, NK cells can directly sense and kill MCMV-infected cells. The loss of any one of these responses increases susceptibility to infection. However, the relative importance of these antiviral immune responses and how they are related remain unclear. In humans, while IFN-I responses are essential, MyD88 is dispensable for antiviral immunity. Hence, a higher redundancy has been proposed in the mechanisms promoting protective immune responses against systemic infections by herpes viruses during natural infections in humans. It has been assumed, but not proven, that mice fail to mount protective MyD88-independent IFN-I responses. In humans, the mechanism that compensates MyD88 deficiency has not been elucidated. To address these issues, we compared resistance to MCMV infection and immune responses between mouse strains deficient for MyD88, the IFN-I receptor and/or Ly49H. We show that selective depletion of pDC or genetic deficiencies for MyD88 or TLR9 drastically decreased production of IFN-I, but not the protective antiviral responses. Moreover, MyD88, but not IFN-I receptor, deficiency could largely be compensated by Ly49H-mediated antiviral NK cell responses. Thus, contrary to the current dogma but consistent with the situation in humans, we conclude that, in mice, in our experimental settings, MyD88 is redundant for IFN-I responses and overall defense against a systemic herpes virus infection. Moreover, we identified direct NK cell sensing of infected cells as one mechanism able to compensate for MyD88 deficiency in mice. Similar mechanisms likely contribute to protect MyD88- or IRAK4-deficient patients from viral infections.


title: Discovery of a highly divergent hepadnavirus in shrews from China

text: Abstract Limited sampling means that relatively little is known about the diversity and evolutionary history of mammalian members of the Hepadnaviridae (genus Orthohepadnavirus). An important case in point are shrews, the fourth largest group of mammals, but for which there is limited knowledge on the role they play in viral evolution and emergence. Here, we report the discovery of a novel shrew hepadnavirus. The newly discovered virus, denoted shrew hepatitis B virus (SHBV), is divergent to be considered a new species of Orthohepadnavirus. Phylogenetic analysis revealed that these viruses were usually most closely related to TBHBV (tent-making bat hepatitis B virus), known to be able to infect human hepatocytes, and had a similar genome structure, although SHBV fell in a more basal position in the surface protein phylogeny. In sum, these data suggest that shrews are natural hosts for hepadnaviruses and may have played an important role in their long-term evolution.


title: COVID-19 pandemic: Response plan by the Johns Hopkins Aramco Healthcare inpatient pharmacy department

text: The coronavirus disease 2019 (COVID-19) is an ongoing pandemic having caused a major health care crises across the globe.Pharmacy professionals are considered vital in preparation for optimal response to the COVID-19 pandemic. Therefore, in response to the estimated potential impact of COVID-19 on Johns Hopkins Aramco Healthcare (joint venture between Saudi Aramco and Johns Hopkins Medicine International), several initiatives were taken by the hospital's inpatient pharmacy department with focus on infection control, staffing, meeting clinical operational challenges, ethics, increased utilization of automation, and maintenance of employee wellness to prepare for this challenge. The plan implemented by the inpatient pharmacy department was prepared while incorporating information and recommendations from leading pharmacy organizations, ministry of health, institute's experience in battling another similar coronavirus (the Middle East respiratory syndrome–coronavirus) previously, and updated scientific research. The key focus areas include development of an institutionalized COVID-19 protocol, measures to improve infection control when handling and dispensing medications, modified staffing plan, system changes in peri-operative areas, keeping pharmacy professionals updated about new and scientific researches, increased utilization of automation, clinical interventions by pharmacist ensuring appropriate utilization of medications while monitoring for drug-drug interactions, adverse drug event prevention, and preparing for handling drug shortages. By implementing a robust plan, pharmacy professionals continue to show that they are an integral member of inter-professional health care teams.


title: Drinking to Cope with the Pandemic: The Unique Associations of COVID-19-Related Perceived Threat and Psychological Distress to Drinking Behaviors in American Men and Women

text: The 2019 Coronavirus pandemic has brought about significant and unprecedented changes to the modern world, including stay-at-home orders, high rates of unemployment, and more than a hundred thousand deaths across the United States. Derived from the self-medication hypothesis, this research explored how perceived threat and psychological distress related to the COVID-19 pandemic are associated with drinking behavior among an American sample of adults. We also evaluated whether links between COVID-19-related perceived threat and psychological distress with drinking behavior are different for men and women. Participants (N=754; 50% women) completed an online Qualtrics Panels study between April 17(th) and 23(rd), 2020. Results suggested that psychological distress related to the COVID-19 pandemic was consistently related to alcohol use indices, and moderation results indicated this pattern was significant only among women for number of drinks consumed during the recent heaviest drinking occasion and number of drinks consumed on a typical evening. COVID-related distress’ link to frequency of drinking and heavy drinking episodes was not different for men and women. Our results suggest that continued monitoring, particularly among women, should be conducted as this pandemic continues to evolve to identify the long-term public health impacts of drinking to cope with COVID-19 distress.


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title: Tropism and innate host responses of a novel avian influenza A H7N9 virus: an analysis of ex-vivo and in-vitro cultures of the human respiratory tract

text: BACKGROUND: Since March, 2013, an avian-origin influenza A H7N9 virus has caused severe pneumonia in China. The aim of this study was to investigate the pathogenesis of this new virus in human beings. METHODS: We obtained ex-vivo cultures of the human bronchus, lung, nasopharynx, and tonsil and in-vitro cultures of primary human alveolar epithelial cells and peripheral blood monocyte-derived macrophages. We compared virus tropism and induction of proinflammatory cytokine responses of two human influenza A H7N9 virus isolates, A/Shanghai/1/2013 and A/Shanghai/2/2013; a highly pathogenic avian influenza H5N1 virus; the highly pathogenic avian influenza H7N7 virus that infected human beings in the Netherlands in 2003; the 2009 pandemic influenza H1N1 virus, and a low pathogenic duck H7N9 virus that was genetically different to the human disease causing A H7N9 viruses. FINDINGS: Both human H7N9 viruses replicated efficiently in human bronchus and lung ex-vivo cultures, whereas duck/H7N9 virus failed to replicate in either. Both human A H7N9 viruses infected both ciliated and non-ciliated human bronchial epithelial cells and replicated to higher titres than did H5N1 (p<0·0001 to 0·0046) and A/Shanghai/1/2013 replicated to higher titres than did H7N7 (p=0·0002–0·01). Both human A H7N9 viruses predominantly infected type II alveolar epithelial cells and alveolar macrophages in the human lung and replicated to higher titres than did H5N1 (p<0·0001 to 0·0078); A/Shanghai/1/2013 replicated to higher titres than did H1N1 (p=0·0052–0·05) and H7N7 (p=0·0031–0·0151). Human H7N9 viruses were less potent inducers of proinflammatory cytokines compared with H5N1 virus. INTERPRETATION: Collectively, the results suggest that the novel H7N9 viruses are better adapted to infect and replicate in the human conducting and lower airways than are other avian influenza viruses, including H5N1, and pose an important pandemic threat. FUNDING: Area of Excellence Scheme of the University Grants Committee (AoE/M-12/96), Hong Kong Special Administrative Region.


title: Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l’épidémie à SARS-CoV-2

text: Résumé La pandémie 2019–20 liée au coronavirus (SARS-CoV-2 ; severe acute respiratory syndrome coronavirus 2) a des conséquences dramatiques sur les populations en termes de morbi-mortalité et en terme social, le confinement général de près de la moitié de la population mondiale étant une situation inédite dans l’histoire, dont il est difficile aujourd’hui de mesurer l’impact aux niveaux individuel et collectif. Elle touche plus spécifiquement des personnes présentant différents facteurs de risque, qui sont plus fréquents chez les patients souffrant de troubles psychiatriques. Nous avons pratiqué une revue de la littérature visant à permettre d’évaluer le rapport bénéfice/risque spécifique des traitements psychotropes chez des patients souffrant de COVID-19 (coronavirus disease 2019). Sur le plan clinique, les symptômes évocateurs de la COVID-19 (fièvre, toux, dyspnée, signes digestifs) peuvent être provoqués par différents psychotropes et imposent une vigilance pour éviter faux négatifs et faux positifs. Chez les patients atteints, les psychotropes doivent être maniés avec prudence notamment chez les sujets âgés, en prenant en compte le risque pulmonaire. Lithium et Clozapine, qui sont des médicaments de référence dans le trouble bipolaire et la schizophrénie résistante, justifient une attention spécifique. Le sevrage tabagique nécessaire dans les situations d’insuffisance respiratoire justifie un ajustement posologique pour éviter une mauvaise tolérance des traitements habituels. Les traitements symptomatiques utilisés dans la COVID-19 ont de fréquentes interactions avec les psychotropes les plus utilisés. S’il n’existe pas de traitement curatif de l’infection au SARS-CoV-2, les interactions des différentes molécules actuellement testées avec plusieurs classes de psychotropes (antidépresseurs, antipsychotiques) sont importantes à prendre en compte du fait de risque de modification de la conduction cardiaque. Les connaissances spécifiques sur la COVID-19 restent pauvres aujourd’hui, mais il faut recommander la rigueur, dans ce contexte, lors du maniement des psychotropes, pour éviter de rajouter, chez les patients souffrant de troubles psychiatriques, potentiellement vulnérables dans le contexte épidémique, un risque iatrogène ou de perte d’efficacité. Abstract The 2019–20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage – in case of minimal infectious signs and in a situation, which does not allow rapid control – should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.


title: TMV recombinants encoding fused foreign transmembrane domains to the CP subunit caused local necrotic response on susceptible tobacco

text: Abstract With regard to the effects of various foreign peptides fused to the coat protein subunits on the infectivity of corresponding TMV recombinants, some of TMV recombinants were found to induce necrotic local lesions on the inoculated leaves of susceptible tobacco. This paper reported that there existed a group of TMV recombinants in which the fused foreign peptides contained a transmembrane domain according to the predictions by three programs of SOSUI, TMpred and DAS. Further studies showed for the first time that a foreign transmembrane domain in a fused peptide of the corresponding TMV recombinant would result in the local lesions on the susceptible tobacco leaves. In addition, it was concluded that none of the TMV recombinants that systematically infected susceptible tobacco contained a transmembrane domain in the coat protein subunits.


title: Disaster preparedness lessons learned and future directions for education: Results from focus groups conducted at the 2006 APIC Conference

text: BACKGROUND: Infection control professionals (ICP) who have experienced disaster response have not been assessed in terms of the lessons they have learned, gaps they perceive in disaster preparedness, and their perceived priorities for future emergency response training. METHODS: Focus groups were conducted at the APIC 2006 Conference to evaluate ICPs' perceived needs related to disaster planning topics, products they feel are needed for education and reference materials, and lessons learned from past disasters. RESULTS: ICPs' role in disaster preparedness and response is essential, even in noninfectious disease emergencies. Infection control issues in shelters, such as overcrowding, foodborne illness, lack of restroom facilities, inadequate environmental cleaning procedures and products, difficulty assessing disease outbreaks in shelters, inability to isolate potentially contagious patients, and too few hand hygiene supplies can contribute to secondary disease transmission. Other important topics on which ICPs need to be trained include surge capacity, employee health and safety, incident command system, educating responders and the public on disaster preparedness, addressing changing standards/recommendations, and partnering with public health. ICPs need quick reference materials, such as checklists, templates, tool kits, and algorithms to better equip them for disaster response. CONCLUSION: Infection control must continue to partner with public health and other responding agencies to address gaps in disaster planning.


Reacting to the emergence of swine-origin influenza A H1N1


title: Two-week, repeated inhalation exposure of F344 N rats and B6C3F1 mice to ferrocene

text: Abstract Ferrocene (dicyclopentadienyl iron; CAS No. 102-54-5) is a relatively volatile, organometallic compound used as a chemical intermediate, a catalyst, and as an antiknock additive in gasoline. It is of particular interest because of its structural similarities to other metallocenes that have been shown to be carcinogenic. F344 N rats and B6C3F1 mice were exposed to 0, 2.5, 5.0, 10, 20, and 40 mg ferrocene vapor/m3, 6 hr/day for 2 weeks. During these exposures, there were no mortality and no observable clinical signs of ferrocene-related toxicity in any of the animals. At the end of the exposures, male rats exposed to the highest level of ferrocene had decreased body-weight gains relative to the weight gained by filtered air-exposed control rats, while body-weight gains for all groups of both ferrocene- and filtered air-exposed female rats were similar. Male mice exposed to the highest level of ferrocene also had decreased body-weight gains, relative to controls, while female mice had relative decreases in body-weight gains at the three highest exposure levels. Male rats had a slight decrease in relative liver weight at the highest level of exposure, whereas no relative differences in organ weights were seen in female rats. Male mice had exposure-relative decreases in liver and spleen weights, and an increase in thymus weights, relative to controls. For female mice, relative decreases in organ weights were seen for brain, liver, and spleen. No exposure-related gross lesions were seen in any of the rats or mice at necropsy. Histopathological examination was done only on the nasal turbinates, lungs, liver, and spleen. The only exposure-related finding was histopathologic lesions in the nasal turbinates of both species. These lesions were primarily centered in the olfactory epithelium and were morphologically diagnosed as subacute, necrotizing inflammation. Nasal lesions were observed in all ferrocene-exposed animals and differed only in severity, which was dependent on the exposure concentration. In vitro metabolism studies of ferrocene showed that nasal tissue, particularly the olfactory epithelium, had ∼ 10 times higher “ferrocene hydroxylating” activity than did liver tissue from the same animals. These results suggest that the mechanism of ferrocene toxicity may be the intracellular release of ferrous ion through ferrocene metabolism, followed by iron-catalyzed lipid peroxidation of cellular membranes.


title: Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)(†)

text: Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim–sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, β-d-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.


title: ESMO Clinical Research Observatory (ECRO): improving the efficiency of clinical research through rationalisation of bureaucracy

text: During the last years, there has been a dramatic increase in the administrative and bureaucratic burden associated with clinical research, which has clearly had an impact on its overall efficiency and on the activity of clinical investigators and research teams. Indeed, the supervision of the adherence of clinical research to Good Clinical Practice (GCP) guidelines and legal regulations is of the utmost importance. Yet, while such regulations have remained largely unchanged during recent years, the number of administrative tasks and their complexity have grown markedly, as supported by the results of a survey performed among 940 clinical investigators that we report in this manuscript. Therefore, many investigators believe that it has become necessary to undertake a rigorous analysis of the causes and consequences of this issue, and to create a conduit to channel the advice from experienced investigators regarding clinical research procedures, in order to improve them. Based on these premises, ESMO has launched the ESMO Clinical Research Observatory (ECRO), a task force that will analyse different aspects of clinical research. ECRO will aim to provide the views of ESMO on clinical research procedures based on the feedback from clinical investigators, under complete adherence to the Declaration of Helsinki, the GCP guidelines and any other applicable legal regulations, while at the same time showing profound respect for all the stakeholders involved in clinical research. This manuscript provides the background and rationale for the creation of ECRO, its planned activity and an analysis of the current administrative burden in clinical research with recommendations to rationalise it. Indeed, we expect that this effort shall lead to a relevant improvement in the care of patients and in the development of clinical research.


title: Chapter 28 Antiprotozoal Drugs

text: Abstract The Side Effects of Drugs Annuals is a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meyler's Side Effects of Drugs: the International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the July 2013 to December 2014 publications on antiprotozoal drugs covers various antimalarial drugs (4-aminoquinolines chloroquine and hydroxychloroquine, mefloquine, pyrimethamine, proguanil hydrochloride and atovaquone, quinine, artesunate, the combination of artesunate+pyronaridine, metronidazole and ornidazole). This review describes changes in the pharmacokinetics of antimalarial drugs, particularly first-line regimens of artemisinin-based compounds, lumefantrine, chloroquine and pyrimethamine+sulphadoxine that occur in pregnancy.


Where have all the hip fractures gone?


title: Status Presens of Antiviral Drugs And Strategies: Part I: DNA Viruses and Retroviruses

text: More than 40 compounds have been formally licensed for clinical use as antiviral drugs, and half of these are used for the treatment of HIV infections. The others have been approved for the therapy of herpesvirus (HSV, VZV, CMV), hepadnavirus (HBV), hepacivirus (HCV) and myxovirus (influenza, RSV) infections. New compounds are in clinical development or under preclinical evaluation, and, again, half of these are targeting HIV infections. Yet, quite a number of important viral pathogens (i.e. HPV, HCV, hemorrhagic fever viruses) remain in need of effective and/or improved antiviral therapies.


title: Development of transgenic mice expressing a coronavirus-specific public CD4 T cell receptor

text: Mice that are transgenic (Tg) for T cell receptor (TCR) expression are used extensively to analyze longitudinal T cell responses during effector and memory phases of the T cell response. Generation of TCR Tg mice generally requires T cell stimulation and cloning in vitro prior to amplification, processes which introduce biases into selection of the TCR that is ultimately chosen for TCR Tg mouse generation. Here we describe an alternative approach that involves no T cell stimulation or propagation in vitro. We generated mice that were transgenic for a TCR responding to a CD4 T cell epitope (epitope M133) that is immunodominant in mice infected with a neurotropic coronavirus, the JHM strain of mouse hepatitis virus. The CD4 T cell response to epitope M133 is of particular interest because it may be pathogenic, protective or regulatory, depending upon the physiological setting. We applied an iterative process in which we identified a TCR-β chain expressed by all mice that were examined (‘public sequence’). This TCR-β chain was introduced into bone marrow cells with a lentivirus vector, generating TCR-β retrogenic mice. A TCR-α chain that paired with this TCR-β was then identified and used to generate a second set of TCR (α/β) retrogenic mice. After demonstrating that these cells were functional and responded to epitope M133, these TCR chains were used to generate an epitope M133-specific TCR Tg mouse. This method should be generally useful for engineering TCR Tg mice without introduction of bias caused by in vitro manipulation and propagation.


title: Management of patients infected with airborne-spread diseases: An algorithm for infection control professionals

text: BACKGROUND: Many US hospitals lack the capacity to house safely a surge of potentially infectious patients, increasing the risk of secondary transmission. Respiratory protection and negative-pressure rooms are needed to prevent transmission of airborne-spread diseases, but US hospitals lack available and/or properly functioning negative-pressure rooms. Creating new rooms or retrofitting existing facilities is time-consuming and expensive. METHODS: Safe methods of managing patients with airborne-spread diseases and establishing temporary negative-pressure and/or protective environments were determined by a literature review. Relevant data were analyzed and synthesized to generate a response algorithm. RESULTS: Ideal patient management and placement guidelines, including instructions for choosing respiratory protection and creating temporary negative-pressure or other protective environments, were delineated. Findings were summarized in a treatment algorithm. CONCLUSION: The threat of bioterrorism and emerging infections increases health care's need for negative-pressure and/or protective environments. The algorithm outlines appropriate response steps to decrease transmission risk until an ideal protective environment can be utilized. Using this algorithm will prepare infection control professionals to respond more effectively during a surge of potentially infectious patients following a bioterrorism attack or emerging infectious disease outbreak.


title: Depression after Exposure to Stressful Events: Lessons Learned from the SARS Epidemic

text: AIM: To examine, among hospital employees exposed to an outbreak of severe acute respiratory syndrome (SARS), post-outbreak levels of depressive symptoms, and the relationship between those depressive symptom levels and the types of outbreak event exposures experienced. METHODS: In 2006, randomly selected employees (n = 549) of a hospital in Beijing were surveyed concerning their exposures to the city’s 2003 SARS outbreak, and the ways in which the outbreak had affected their mental health. Subjects were assessed on sociodemographic factors, on types of exposure to the outbreak, and on symptoms of post-traumatic stress disorder (PTSD) and depression. RESULTS: The results of multinomial regression analyses showed that, with other relevant factors controlled for, being single, having been quarantined during the outbreak, having been exposed to other traumatic events prior to SARS, and perceived SARS-related risk level during the outbreak were found to increase the odds of having a high level of depressive symptoms three years later. Altruistic acceptance of risk during the outbreak was found to decrease the odds of high post-outbreak depressive symptom levels. CONCLUSIONS: Policy makers and mental health professionals working to prepare for potential disease outbreaks should be aware that the experience of being quarantined can, in some cases, lead to long-term adverse mental health consequences.


title: Specific Nucleotide Changes in the Subgenomic Promoter Region Influence Infectivity of the Sindbis Virus

text: Transcription of the subgenomic mRNA of Sindbis virus (SINV) is initiated at a subgenomic promoter (SP). Alignment of SINV sequences identified a 68-nucleotide conserved domain spanning −19 to +49 relative to the subgenomic mRNA start site. Nucleotide T or C is present at −18 or +49 in all known SINVs while a Sindbis-like virus XJ-160 has an A or T at a corresponding position. Our results indicate that deletion or substitution of the T at +49 decreased the activity of SP, while substituting T for A at −18 did not decrease the activity of SP or genetic stability of recombinant SINV.


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title: Promising inhibitors of main protease of novel corona virus to prevent the spread of COVID-19 using docking and molecular dynamics simulation

text: Coronavirus disease-2019 (COVID-19) is a global health emergency and the matter of serious concern, which has been declared a pandemic by WHO. Till date, no potential medicine/ drug is available to cure the infected persons from SARS-CoV-2. This deadly virus is named as novel 2019-nCoV coronavirus and caused coronavirus disease, that is, COVID-19. The first case of SARS-CoV-2 infection in human was confirmed in the Wuhan city of the China. COVID-19 is an infectious disease and spread from man to man as well as surface to man . In the present work, in silico approach was followed to find potential molecule to control this infection. Authors have screened more than one million molecules available in the ZINC database and taken the best two compounds based on binding energy score. These lead molecules were further studied through docking against the main protease of SARS-CoV-2. Then, molecular dynamics simulations of the main protease with and without screened compounds were performed at room temperature to determine the thermodynamic parameters to understand the inhibition. Further, molecular dynamics simulations at different temperatures were performed to understand the efficiency of the inhibition of the main protease in the presence of the screened compounds. Change in energy for the formation of the complexes between the main protease of novel coronavirus and ZINC20601870 as well ZINC00793735 at room temperature was determined on applying MM-GBSA calculations. Docking and molecular dynamics simulations showed their antiviral potential and may inhibit viral replication experimentally. Communicated by Ramaswamy H. Sarma


title: Cough aerosol in healthy participants: fundamental knowledge to optimize droplet-spread infectious respiratory disease management

text: BACKGROUND: The Influenza A H1N1 virus can be transmitted via direct, indirect, and airborne route to non-infected subjects when an infected patient coughs, which expels a number of different sized droplets to the surrounding environment as an aerosol. The objective of the current study was to characterize the human cough aerosol pattern with the aim of developing a standard human cough bioaerosol model for Influenza Pandemic control. METHOD: 45 healthy non-smokers participated in the open bench study by giving their best effort cough. A laser diffraction system was used to obtain accurate, time-dependent, quantitative measurements of the size and number of droplets expelled by the cough aerosol. RESULTS: Voluntary coughs generated droplets ranging from 0.1 - 900 microns in size. Droplets of less than one-micron size represent 97% of the total number of measured droplets contained in the cough aerosol. Age, sex, weight, height and corporal mass have no statistically significant effect on the aerosol composition in terms of size and number of droplets. CONCLUSIONS: We have developed a standard human cough aerosol model. We have quantitatively characterized the pattern, size, and number of droplets present in the most important mode of person-to-person transmission of IRD: the cough bioaerosol. Small size droplets (< 1 μm) predominated the total number of droplets expelled when coughing. The cough aerosol is the single source of direct, indirect and/or airborne transmission of respiratory infections like the Influenza A H1N1 virus. STUDY DESIGN: Open bench, Observational, Cough, Aerosol study


title: Plasmonic and Superhydrophobic Self-Decontaminating N95 Respirators

text: [Image: see text] The COVID-19 pandemic is endangering the world due to the spread of respiration droplets with viruses. Medical workers and frontline staff need to wear respirators to protect themselves from breathing in the virus-containing respiration droplets. The most frequently used state-of-the-art respirators are of N95 standard; however, they lack self-decontamination capabilities. In addition, the viruses and bacteria can accumulate on the respirator surfaces, possessing high risks to the wearers over long-term usage. Photothermal decontamination is a contactless, fast, low-cost, and widely available method, capable of decontaminating the respirators. Herein, we report a plasmonic photothermal and superhydrophobic coating on N95 respirators, possessing significantly better protection than existing personal protection equipment. The plasmonic heating can raise the surface temperature to over 80 °C for this type of respirator within 1 min of sunlight illumination. The superhydrophobic features prohibit respiration droplets from accumulating on the respirator surfaces. The presence of the silver nanoparticles can provide additional protection via the silver ion’s disinfection toward microbes. These synergistic features of the composite coatings provide the N95 respirator with better protection and can inspire experts from interdisciplinary fields to develop better personal protection equipment to fight the COVID-19 pandemic.


Correlation between viral RNA shedding and serum antibodies in COVID-19 patients


title: Sequence of the membrane protein gene from avian coronavirus IBV

text: Abstract cDNA clones prepared from genomic RNA of coronavirus IBV have been sequenced. The nucleotide sequence for the complete 5' region of mRNA C, which is not present in mRNAs A and B, has been determined. A sequence of 1224 bases is presented which contains a long open reading frame predicting a polypeptide of molecular weight 25 443. This is in agreement with the molecular weight of 23 000 reported for the unglycosylated form of the membrane polypeptide.


title: Rapid Detection of 2019 Novel Coronavirus SARS-CoV-2 Using a CRISPR-based DETECTR Lateral Flow Assay

text: An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.


title: Structural Considerations in the Fitness Landscape of a Virus

text: Viral fitness is determined by replication within hosts and transmission between them. We examine how pleiotropic mutations that have antagonistic effects (i.e., antibody evasion vs. receptor binding) on viral replication within hosts can impact viral immune escape in the host population. When the host population is vaccinated, the virus escapes from passive immunity by mutations in the antibody-binding region on the surface of the target protein. However, the reduced ability of the antibody to bind the virus is often accompanied by a reduced ability of the virus to bind the cell receptor because the antibody-binding region overlaps with the receptor-binding domain (RBD). The types of permitted mutations are limited. To investigate the causal relation between a mutation in a viral genome and adaptive evolution of a viral population, we developed a mathematical model that describes the population dynamics of viruses, antibodies, and normal/infected cells within a host. The coefficients describe the binding affinity between the virus and the induced antibody and that between the virus and its receptor. Our knowledge-based index enables us to estimate the effect of a mutation in a binding region on the binding affinity. Using population genetic theory, we evaluated the probability that a mutant is fixed in a host population. The mutations that can be fixed with high probabilities may determine how long a vaccine remains effective. We simulate the adaptive evolution of coronavirus, the etiological agent of severe acute respiratory syndrome, and show that some of mutations in the RBD may have high fixation probabilities in the vaccinated host population.


docid: fihedvms

title: Emerging viral infections in a rapidly changing world

text: Abstract Emerging viral infections in both humans and animals have been reported with increased frequency in recent years. Recent advances have been made in our knowledge of some of these, including severe acute respiratory syndrome-associated coronavirus, influenza A virus, human metapneumovirus, West Nile virus and Ebola virus. Research efforts to mitigate their effects have concentrated on improved surveillance and diagnostic capabilities, as well as on the development of vaccines and antiviral agents. More attention needs to be given to the identification of the underlying causes for the emergence of infectious diseases, which are often related to anthropogenic social and environmental changes. Addressing these factors might help to decrease the rate of emergence of infectious diseases and allow the transition to a more sustainable society.


title: Replication of murine coronavirus requires multiple cysteines in the endodomain of spike protein

text: Abstract A conserved cysteine-rich motif located between the transmembrane domain and the endodomain is essential for membrane fusion and assembly of coronavirus spike (S) protein. Here, we proved that three cysteines within the motif, but not dependent on position, are minimally required for the survival of the recombinant mouse hepatitis virus. When the carboxy termini with these mutated motifs of S proteins were respectively introduced into a heterogeneous protein, both incorporation into lipid rafts and S-palmitoylation of these recombinant proteins showed a similar quantity requirement to cysteine residues. Meanwhile, the redistribution of these proteins on cellular surface indicated that the absence of the positively charged rather than cysteine residues in the motif might lead the dramatic reduction in syncytial formation of some mutants with the deleted motifs. These results suggest that multiple cysteine as well as charged residues concurrently improves the membrane-associated functions of S protein in viral replication and cytopathogenesis.


COVID-19 Guideline Modifications as CMS Announces “Opening Up America Again”: Comments from the Society of Surgical Oncology


title: The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis

text: Abstract Objectives An outbreak of novel coronavirus in 2019 threatens the health of people, and there is no proven pharmacological treatment. Although corticosteroids were widely used during outbreaks of severe acute respiratory syndrome and Middle East respiratory syndrome, their efficacy remainedhighly controversial. We aimed to further evaluate the influence of corticosteroids on patients with coronavirus infection. Methods We conducted a comprehensive search of literature published in PubMed, Embase, Cochrane library, and China National Knowledge Infrastructure (CNKI) from January 1, 2002 to March 15, 2020. All statistical analyses in this study were performed on stata14.0. Results A total of 5270 patients from 15 studies were included in this meta-analysis. The result indicated that critical patients were more likely to require corticosteroids therapy (risk ratio [RR] = 1.56, 95% confidence interval [CI] = 1.28-1.90, P<0.001). However, corticosteroid treatment was associated with higher mortality (RR = 2.11, 95%CI = 1.13-3.94, P = 0.019), longer length of stay (weighted mean difference [WMD] = 6.31, 95%CI = 5.26–7.37, P<0.001), a higher rate of bacterial infection (RR = 2.08, 95%CI = 1.54–2.81, P<0.001), and hypokalemia (RR = 2.21, 95%CI = 1.07–4.55, P = 0.032) but not hyperglycemia (RR = 1.37, 95%CI=0.68–2.76, P = 0.376) or hypocalcemia (RR = 1.35, 95%CI = 0.77–2.37, P = 0.302). Conclusions Patients with severe conditions are more likely to require corticosteroids. Corticosteroid use is associated with increased mortality in patients with coronavirus pneumonia.


title: Emerging and re-emerging virus infections in neonates and young pediatric patients

text: ABSTRACT The epidemiology of virus infections has changed dramatically in Europe in recent years due to ecologic, anthropologic and biologic factors such as: i) climate modifications, ii) global exchange of goods and international travel, iii) increased immigration flux from Africa, South America, the Middle East and Asia, iv) reduction of cultivated areas, and v) emergence and re-emergence of human viruses from zoonotic reservoirs. In addition, recent technical advancements have allowed the identification of previously unrecognized autochthonous viral species. Thus, at present, the technical and cultural challenge is to recognize infections caused by viruses not normally circulating in our geographical region (both as imported cases or potential local outbreaks), sustained by recently discovered autochthonous viruses or due to recognized viruses which are no longer widespread in Western Europe due to past vaccination campaigns.


EP News: Clinical


Correction: Case characteristics among Middle East respiratory syndrome coronavirus outbreak and non-outbreak cases in Saudi Arabia from 2012 to 2015


title: Detection of respiratory viruses in gargle specimens of healthy children

text: Abstract Background Respiratory tract viral infection is one of the most common and important diseases in children. Polymerase chain reaction (PCR) tests are often used to detect viruses in samples, it is difficult to interpret the clinical significance of PCR positivity, which may reflect a past, imminent or active asymptomatic infection due to their high sensitivity. Although single respiratory viruses have been detected in samples from children with symptoms, other respiratory viruses can also be detected simultaneously. However, the clinical importance of these findings for the symptoms is not known. Objectives To investigate the prevalence of respiratory viruses among children without any symptoms such as acute respiratory illness and/or fever. Study design From week twenty-five 2013 to week twenty-six 2014, gargle samples were collected from children once a week and these samples were subjected to real-time PCR to detect respiratory viruses. On each sampling day, we asked the parents about their children’s health condition. Results Among the 286 samples collected, 200 were from asymptomatic children. In the asymptomatic condition, human parechovirus, adenovirus, enterovirus, rhinovirus, coronavirus 229E and HKU1 were observed in 45 episodes. In samples from symptomatic children, parainfluenza viruses, respiratory syncytial virus and coronavirus OC43 were detected in addition to those mentioned above. Conclusions Various viruses of different species were detected in the specimens from the children regardless of their health status. It might be speculated that host factors such as the function of the immune system influence the clinical outcome of the infection. However, this needs to be studied further.


title: Using Routine Surveillance Data to Estimate the Epidemic Potential of Emerging Zoonoses: Application to the Emergence of US Swine Origin Influenza A H3N2v Virus

text: BACKGROUND: Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations. METHODS AND FINDINGS: Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1−G; otherwise R can be estimated by 1−F when the case detection rate is low. In more general cases, bounds on R can still be derived. CONCLUSIONS: We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary


title: The three domains of public health: An internationally relevant basis for public health education?

text: Summary By focusing on the Masters of Public Health course, this study took a pragmatic approach to exploring the interface between public health education and public health practice. The commonly utilized ‘three domains of practice’ framework could provide a robust and explicit link between educational provision and practice for public health. This model provides the workforce, the university, the students and the potential funders of the course with an easily comprehensible framework for understanding how the modules of an MSc can support the development of competency within the context of practice.


title: Clinicopathological findings associated with feline infectious peritonitis in Sydney, Australia: 42 cases (1990–2002)

text: Objectives To review the clinicopathological findings in naturally‐occurring, histopathologically confirmed cases of feline infectious peritonitis in client‐owned cats in Sydney, Australia, with the purpose of identifying factors assisting in the diagnosis of this complex disease syndrome and to characterise the disease as it occurs in this region. Design Retrospective clinical study: the clinical records of all cats with histopathologically confirmed feline infectious peritonitis at the University Veterinary Centre Sydney and a private cat hospital in Sydney between 1990 and 2002 were reviewed for signalment, history, physical findings, diagnostic test results and the distribution of histological lesions throughout the body at necropsy. Results Forty‐two cats met the inclusion criteria. Significant features of this study that unique to the contemporary literature are i) the over‐representation of certain breeds (Burmese, Australian Mist, British Shorthaired, and Cornish Rex) and the under‐representation of other breeds (Domestic Shorthaired, Persian); ii) the overrepresentation of males; iii) the tendency for effusive disease in Australian Mist cats and non‐effusive disease in Burmese; iv) the even age distribution of disease seen in cats older than 2 years‐of‐age; and v) the presence of fulminant immune‐mediated haemolytic anaemia in two cats in this study. Conclusion The study highlights the diverse range of clinical manifestations and the complexities experienced by clinicians in diagnosing this fatal disease. Some aspects of the epidemiology and clinical manifestations of feline infectious peritonitis appear different to the disease encountered in Europe and North America, most notably the over‐representation of specific breeds and the presence of immune‐mediated haemolytic anaemia.


title: Assessing Differential Impacts of COVID-19 on Black Communities

text: PURPOSE: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. METHODS: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. RESULTS: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. CONCLUSIONS: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.


docid: sgqumdpv

title: Risk perception in Northeast Asia

text: Multi-country surveys of the public’s perception of risk using the same questionnaire were sequentially implemented from April to December 2006 in Japan, China, and South Korea. Statistical analyses, such as traditional mean tests, rank order tests, two-step cluster analysis, and principal component analysis were used to analyze the survey data. The results revealed that Chinese tend to be more tolerant of risk than Japanese and South Koreans. In all three countries, the threats of global warming, cancer, traffic accidents, and fire were perceived as higher-order risks, while infectious diseases and threats from high technology were perceived as lower-order risks. Looking across the entire multi-country sample, we found that Chinese participants perceived greater risk in typhoons, SARS, and drugs; Japanese saw greater risk from gas explosions and potential threats coming over the Internet; while people in all three countries identified earthquakes as a primary risk. These differences in risk perception reflect the natural and socioeconomic conditions in the three countries. Although the study did not emphasize differences in risk perception within countries based on demographic factors such as education, age, and gender, we found that differences based on education and age tended to be greater in China and South Korea than in Japan. We also found that men perceived greater risks than women in China and South Korea, while in Japan it was the opposite with women perceiving greater risks. A comparison of these results with previous studies reveals a bias in past studies toward student samples and indicates the need for more representative samples in multi-country surveys.


title: Role of Infections

text: This article represents a review of the current literature on the role of infection in the pathogenesis of chronic obstructive pulmonary disease (COPD), in stable disease, exacerbations, and pneumonia. It outlines the complex interactions between respiratory pathogens and host immune defenses that underlie the clinical manifestations of infection in COPD.


title: Respiratory infections and asthma

text: Summary Respiratory tract infections caused by both viruses and/or atypical bacteria are involved in the pathogenesis of asthma. In particular, several viruses such as respiratory syncytial virus, rhinovirus and influenza/parainfluenza viruses may favour the expression of the asthmatic phenotype, being also implicated in the induction of disease exacerbations. Within this pathological context, a significant role can also be played by airway bacterial colonizations and infections due to Chlamydiae and Mycoplasms. All these microbial agents probably interfere with complex immunological pathways, thus contributing to induce and exacerbate asthma in genetically predisposed individuals.


title: Molecular characterisation of the virulent canine coronavirus CB/05 strain

text: Abstract This paper characterises a virulent strain (CB/05) of canine coronavirus (CCoV) isolated from the internal organs of pups that had died of a systemic disease without evidence of other common canine pathogens. High viral RNA titres were detected in the internal organs by a real-time RT-PCR assay specific for CCoV type II. Sequence analysis of the 3′ end (8.7kb) of the genomic RNA of strain CB/05 revealed conserved structural as well as non-structural proteins, with the exception of a truncated form of non-structural protein 3b. The exceptional form was due to a 38-nucleotide deletion and a frame shift in ORF3b that introduced an early stop codon. By phylogenetic analysis of the structural proteins, the spike (S) protein was found to cluster with feline coronavirus type II strain 79-1683, whereas, the envelope (E), membrane (M) and nucleocapsid (N) proteins segregated together with the reference strain Purdue of transmissible gastroenteritis virus of swine.


title: Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition

text: Since the outbreak of the COVID-19 pandemic in December 2019 and its rapid spread worldwide, the scientific community has been under pressure to react and make progress in the development of an effective treatment against the virus responsible for the disease. Here, we implement an original virtual screening (VS) protocol for repositioning approved drugs in order to predict which of them could inhibit the main protease of the virus (M-pro), a key target for antiviral drugs given its essential role in the virus’ replication. Two different libraries of approved drugs were docked against the structure of M-pro using Glide, FRED and AutoDock Vina, and only the equivalent high affinity binding modes predicted simultaneously by the three docking programs were considered to correspond to bioactive poses. In this way, we took advantage of the three sampling algorithms to generate hypothetic binding modes without relying on a single scoring function to rank the results. Seven possible SARS-CoV-2 M-pro inhibitors were predicted using this approach: Perampanel, Carprofen, Celecoxib, Alprazolam, Trovafloxacin, Sarafloxacin and ethyl biscoumacetate. Carprofen and Celecoxib have been selected by the COVID Moonshot initiative for in vitro testing; they show 3.97 and 11.90% M-pro inhibition at 50 µM, respectively.


title: Reducing the Impact of Viral Respiratory Infections in Children

text: This article reviews the epidemiology and clinical aspects of the major viral causes of upper and lower respiratory tract disease in children. Particular emphasis is placed on prevention and control of viral disease through the use of vaccines and antiviral agents. Evolution of new viral pathogens, such as avian influenza virus and the SARS-CoV, are discussed.


Besides the climate model, other variables driving the COVID-19 spread in Brazil()


Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges


title: Organizational challenges, volumes of oncological activity, and patients' perception during the SARS-CoV-2 epidemic

text: BACKGROUND: On February 23(rd), the 1(st) case of SARS-CoV-2 infection was diagnosed at the University Hospital Trust of Verona, Italy. On March 13(th), the Oncology Section was converted into a 22-inpatient beds COVID unit and we reshaped our organization to face SARS-CoV-2 epidemic, while maintaining oncological activities. METHODS: We tracked down: i) volumes of oncological activities (January 1(st) - March 31(st), 2020 versus the same period of 2019), ii) patients' and caregivers' perception, iii) SARS-CoV-2 infection rate in oncology health professionals and SARS-CoV-2 infection-related hospital admissions of "active" oncological patients. RESULTS: As compared with the same trimester in 2019, the overall reduction in total numbers of inpatient admissions, chemotherapy administrations, and specialty visits in January-March 2020 was 8%, 6%, and 3%, respectively; based on the weekly average of daily accesses, reduction in some of the oncological activities became statistically significant from week 11. The overall acceptance of adopted measures, as measured by targeted questionnaires administered to a sample of 241 outpatients, was high (>70%). Overall, 8/85 oncology health professionals tested positive for SARS-CoV-2 infection (all but one employed in the COVID unit, no hospital admissions and no treatment required); among 471 patients admitted for SARS-CoV-2 infection, 7 had an "active" oncological disease (2 died of infection-related complications). CONCLUSIONS: A slight, but statistically significant reduction in oncology activity was registered during the SARS-CoV-2 epidemic peak in Verona, Italy. Organizational and protective measures adopted appear to have contributed to keep infections in both oncological patients and health professionals to a minimum.


docid: teumoxkd

title: Innate immune response to arenaviral infection: a focus on the highly pathogenic New World hemorrhagic arenaviruses

text: Arenaviruses are enveloped, negative-stranded RNA viruses that belong to the family Arenaviridae. This diverse family can be further classified into OW (Old World) and NW (New World) arenaviruses based on their antigenicity, phylogeny, and geographical distribution. Many of the NW arenaviruses are highly pathogenic viruses that cause systemic human infections characterized by hemorrhagic fever and/or neurological manifestations, constituting public health problems in their endemic regions. NW arenavirus infection induces a variety of host innate immune responses, which could contribute to the viral pathogenesis and/or influence the final outcome of virus infection in vitro as well as in vivo. On the other hand, NW arenaviruses have also developed several strategies to counteract the host innate immune response. We will review current knowledge regarding the interplay between the host innate immune response and NW arenavirus infection in vitro and in vivo, with emphasis on viral-encoded proteins and their effect on the type I interferon response.


title: Chapter 10 Cyclic Peptides in Neurological Disorders: The Case of Cyclo(His-Pro)

text: Abstract Communication between and within communities of cells or independent organisms is a crucial prerequisite for species survival. In response to variations in the extracellular environment, the collective behavior of cell populations can be coordinated by regulating community-level gene expression. This mechanism is strongly conserved during evolution, being shared both by bacterial communities and central nervous system cells. Notably, cyclic dipeptides (CDPs) are molecules that are implicated in these quorum sensing behaviors in both settings. Bacteria coordinate their collective behavior by producing CDPs (quorum sensing inducers) that enhance the capacity of individual members of the community to detect these signals and thus amplify the community-level response. In this review, we highlight recent data indicating that strikingly similar molecular mechanisms control communications between glial and neuronal cells to maintain homeostasis in the central nervous system, with a specific focus on the role of the thyrotropin-releasing hormone—derived CDP cyclo(His-Pro) in the protection against neurotoxic insults.


title: Coronavirus infection of rat dorsal root ganglia: Ultrastructural characterization of viral replication, transfer, and the early response of satellite cells

text: Abstract Swine hemagglutinating encephalomyelitis virus (HEV) has been shown to have a capability to gain access to the cell bodies of sensory neurons after peripheral inoculation, resulting in ganglionic infection. It is not clearly understood how this virus is replicated within and released from the sensory neurons, and it remains to know how satellite cells response to the HEV invasion. By ultrastructurally examining HEV-infected rat dorsal root ganglia, we found that HEV in the cell bodies of infected neurons budded from endoplasmic reticulum–Golgi intermediate compartments, and were assembled either individually within small vesicles or in groups within large vesicles. The progeny virions were released from the sensory neurons mainly by smooth-surfaced vesicle-mediated secretory pathway, which occurred predominantly at the perikaryal projections and infoldings of sensory neurons. Released HEV particles were subsequently taken up by the adjacent satellite cells. Almost all virus particles in the cytoplasm of satellite cells were contained in groups within vesicles and lysosome-like structures, suggesting that these glial cells may restrict the local diffusion of HEV. These observations give some insights into the pathogenesis of coronavirus infection and are thought to help understand the interactions between sensory neurons and their satellite cells.


SARS-CoV-2 infection in a psoriatic arthritis patient treated with IL-17 inhibitor


title: Paciente con fiebre y exantema

text: Presentamos el caso de una paciente de 23 años de edad, con fiebre, cefalea, inyección conjuntival bilateral, hepatomegalia dolorosa y exantema macular generalizado con elevación de enzimas hepáticas. Se realizó un estudio serológico que confirmó la sospecha diagnóstica de infección aguda por el virus del sarampión. We report the case of a 23-year old woman with fever, headache, bilateral conjunctival injection, painful hepatomegaly and generalized macular rash with elevated liver enzymes. Acute measles infection was suspected based on the clinical findings and was serologically confirmed.


title: Delivery of RNAi Therapeutics to the Airways—From Bench to Bedside

text: RNA interference (RNAi) is a potent and specific post-transcriptional gene silencing process. Since its discovery, tremendous efforts have been made to translate RNAi technology into therapeutic applications for the treatment of different human diseases including respiratory diseases, by manipulating the expression of disease-associated gene(s). Similar to other nucleic acid-based therapeutics, the major hurdle of RNAi therapy is delivery. Pulmonary delivery is a promising approach of delivering RNAi therapeutics directly to the airways for treating local conditions and minimizing systemic side effects. It is a non-invasive route of administration that is generally well accepted by patients. However, pulmonary drug delivery is a challenge as the lungs pose a series of anatomical, physiological and immunological barriers to drug delivery. Understanding these barriers is essential for the development an effective RNA delivery system. In this review, the different barriers to pulmonary drug delivery are introduced. The potential of RNAi molecules as new class of therapeutics, and the latest preclinical and clinical studies of using RNAi therapeutics in different respiratory conditions are discussed in details. We hope this review can provide some useful insights for moving inhaled RNAi therapeutics from bench to bedside.


title: Human Sentinel Surveillance of Influenza and Other Respiratory Viral Pathogens in Border Areas of Western Cambodia

text: Little is known about circulation of influenza and other respiratory viruses in remote populations along the Thai-Cambodia border in western Cambodia. We screened 586 outpatients (median age 5, range 1–77) presenting with influenza-like-illness (ILI) at 4 sentinel sites in western Cambodia between May 2010 and December 2012. Real-time reverse transcriptase (rRT) PCR for influenza was performed on combined nasal and throat specimens followed by viral culture, antigenic analysis, antiviral susceptibility testing and full genome sequencing for phylogenetic analysis. ILI-specimens negative for influenza were cultured, followed by rRT-PCR for enterovirus and rhinovirus (EV/RV) and EV71. Influenza was found in 168 cases (29%) and occurred almost exclusively in the rainy season from June to November. Isolated influenza strains had close antigenic and phylogenetic relationships, matching vaccine and circulating strains found elsewhere in Cambodia. Influenza vaccination coverage was low (<20%). Western Cambodian H1N1(2009) isolate genomes were more closely related to 10 earlier Cambodia isolates (94.4% genome conservation) than to 13 Thai isolates (75.9% genome conservation), despite sharing the majority of the amino acid changes with the Thai references. Most genes showed signatures of purifying selection. Viral culture detected only adenovirus (5.7%) and parainfluenza virus (3.8%), while non-polio enteroviruses (10.3%) were detected among 164 culture-negative samples including coxsackievirus A4, A6, A8, A9, A12, B3, B4 and echovirus E6 and E9 using nested RT-PCR methods. A single specimen of EV71 was found. Despite proximity to Thailand, influenza epidemiology of these western Cambodian isolates followed patterns observed elsewhere in Cambodia, continuing to support current vaccine and treatment recommendations from the Cambodian National Influenza Center. Amino acid mutations at non-epitope sites, particularly hemagglutinin genes, require further investigation in light of an increasingly important role of permissive mutations in influenza virus evolution. Further research about the burden of adenovirus and non-polio enteroviruses as etiologic agents in acute respiratory infections in Cambodia is also needed.


title: Epidemiology, Co-Infections, and Outcomes of Viral Pneumonia in Adults: An Observational Cohort Study

text: Advanced technologies using polymerase-chain reaction have allowed for increased recognition of viral respiratory infections including pneumonia. Co-infections have been described for several respiratory viruses, especially with influenza. Outcomes of viral pneumonia, including cases with co-infections, have not been well described. This was observational cohort study conducted to describe hospitalized patients with viral pneumonia including co-infections, clinical outcomes, and predictors of mortality. Patients admitted from March 2013 to November 2014 with a positive respiratory virus panel (RVP) and radiographic findings of pneumonia within 48 h of the index RVP were included. Co-respiratory infection (CRI) was defined as any organism identification from a respiratory specimen within 3 days of the index RVP. Predictors of in-hospital mortality on univariate analysis were evaluated in a multivariate model. Of 284 patients with viral pneumonia, a majority (51.8%) were immunocompromised. A total of 84 patients (29.6%) were found to have a CRI with 48 (57.6%) having a bacterial CRI. Viral CRI with HSV, CMV, or both occurred in 28 patients (33.3%). Fungal (16.7%) and other CRIs (7.1%) were less common. Many patients required mechanical ventilation (54%) and vasopressor support (36%). Overall in-hospital mortality was high (23.2%) and readmissions were common with several patients re-hospitalized within 30 (21.1%) and 90 days (36.7%) of discharge. Predictors of in-hospital mortality on multivariate regression included severity of illness factors, stem-cell transplant, and identification of multiple respiratory viruses. In conclusion, hospital mortality is high among adult patients with viral pneumonia and patients with multiple respiratory viruses identified may be at a higher risk.


title: Bat Research Networks and Viral Surveillance: Gaps and Opportunities in Western Asia

text: Bat research networks and viral surveillance are assumed to be at odds due to seemingly conflicting research priorities. Yet human threats that contribute to declines in bat populations globally also lead to increased transmission and spread of bat-associated viruses, which may pose a threat to global health and food security. In this review, we discuss the importance of and opportunities for multidisciplinary collaborations between bat research networks and infectious disease experts to tackle shared threats that jeopardize bat conservation as well as human and animal health. Moreover, we assess research effort on bats and bat-associated viruses globally, and demonstrate that Western Asia has limited published research and represents a gap for coordinated bat research. The lack of bat research in Western Asia severely limits our capacity to identify and mitigate region-specific threats to bat populations and detect interactions between bats and incidental hosts that promote virus spillover. We detail a regional initiative to establish the first bat research network in Western Asia (i.e., the Western Asia Bat Research Network, WAB-Net), with the aim of integrating ecological research on bats with virus surveillance to find “win-win” solutions that promote bat conservation and safeguard public and animal health across the region.


docid: aogqumuf

title: Emergence of a coronavirus infectious bronchitis virus mutant with a truncated 3b gene: functional characterization of the 3b protein in pathogenesis and replication

text: Abstract The subgenomic RNA 3 of IBV has been shown to be a tricistronic mRNA, encoding three products in IBV-infected cells. To explore if the least expressed ORF, ORF 3b, which encodes a nonstructural protein, is evolutionarily conserved and functionally indispensable for viral propagation in cultured cells, the Beaudette strain of IBV was propagated in chicken embryonated eggs for three passages and then adapted to a monkey kidney cell line, Vero. The 3b gene of passage 3 in embryonated eggs and passages 7, 15, 20, 25, 30, 35 50, and 65 in Vero cells were amplified by reverse transcription–polymerase chain reaction and sequenced. The results showed that viral RNA extracted from passages 35, 50, and 65 contained a single A insertion in a 6A stretch of the 3b gene between nucleotides 24075 and 24080, whereas the early passages carried the normal 3b gene. This insertion resulted in a frameshift event and therefore, if expressed, a C-terminally truncated protein. We showed that the frameshifting product, cloned in a plasmid, was expressed in vitro and in cells transfected with the mutant construct. The normal product of the 3b gene is 64 amino acids long, whereas the frameshifting product is 34 amino acids long with only 17 homogeneous amino acid residues at the N-terminal half. Immunofluorescent studies revealed that the normal 3b protein was localized to the nucleus and the truncated product showed a “free” distribution pattern, indicating that the C-terminal portion of 3b was responsible for its nuclear localization. Comparison of the complete genome sequences (27.6 kb) of isolates p20c22 and p36c12 (from passages 20 and 36, respectively) revealed that p36c12 contains three amino acid substitutions, two in the 195-kDa protein (encoded by gene 1) and one in the S protein, in addition to the frameshifting 3b product. Further characterization of the two isolates demonstrated that p36c12 showed growth advantage over p20c22 in both Vero cells and chicken embryos and was more virulent in chicken embryos than p20c22. These results suggest that the 3b gene product is not essential for the replication of IBV.


title: Feline morbillivirus in Northern Italy: prevalence in urine and kidneys with and without renal disease

text: Abstract Feline morbillivirus (FeMV) is an emerging virus that was first described in Hong Kong in 2012. Several reports suggested the epidemiological association of FeMV infection with chronic kidney disease (CKD) in cats. The aim of this study was to investigate the presence and the genetic diversity of FeMV as well as the relationship between FeMV infection and CKD in cats from Northern Italy. Urine (n = 81) and kidney samples (n = 27) from 92 cats admitted to the Veterinary Teaching Hospital of the University of Milan between 2014 and 2017 were investigated for FeMV infection. FeMV RNA was detected in one urine sample (1.23%; 95% CI: 0.03–6.68%) and in two kidneys (7.40%; 95% CI: 0.91–24.28%). FeMV RNA was revealed only in urine or kidneys of cats without evidence of CKD. Phylogenetic analysis showed that the three strains clustered with FeMV strains retrieved from public database, forming a distinct sub-cluster of FeMV. The presence of distinct genotypes of FeMV found in this study is in accordance with previous studies demonstrating that FeMV strains are genetically diverse. A clear relationship between the presence of FeMV infection and CKD in the cats from Northern Italy was not observed, confirming recent reports that do not support the hypothesis that FeMV infection is associated with the development of CKD.


title: IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

text: Emergence of drug resistance among the causative organisms for respiratory tract infections represents a critical challenge to the global health care community. Further, although vaccination can prevent disease, vaccine development is impeded by several factors. Therefore, novel approaches to treat and manage respiratory infections are urgently needed. Passive immunization represents a possible alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk of chicken eggs have previously been used against bacterial and viral infections in human and animals. Their advantages include lack of reaction with mammalian Fc receptors, low production cost, and ease of extraction. Compared to mammalian IgGs, they have higher target specificity and greater binding avidity. They also possess remarkable pathogen-neutralizing activity in the respiratory tract and lungs. In this review, we provide an overview of avian IgYs and describe their potential therapeutic applications for the prevention and treatment of respiratory infections.


Importance of Specimen Type and Quality in Diagnosing Middle East Respiratory Syndrome


title: Review of Non-bacterial Infections in Respiratory Medicine: Viral Pneumonia

text: Abstract Although bacteria are the main pathogens involved in community-acquired pneumonia, a significant number of community-acquired pneumonia are caused by viruses, either directly or as part of a co-infection. The clinical picture of these different pneumonias can be very similar, but viral infection is more common in the pediatric and geriatric populations, leukocytes are not generally elevated, fever is variable, and upper respiratory tract symptoms often occur; procalcitonin levels are not generally affected. For years, the diagnosis of viral pneumonia was based on cell culture and antigen detection, but since the introduction of polymerase chain reaction techniques in the clinical setting, identification of these pathogens has increased and new microorganisms such as human bocavirus have been discovered. In general, influenza virus type A and syncytial respiratory virus are still the main pathogens involved in this entity. However, in recent years, outbreaks of deadly coronavirus and zoonotic influenza virus have demonstrated the need for constant alert in the face of new emerging pathogens. Neuraminidase inhibitors for viral pneumonia have been shown to reduce transmission in cases of exposure and to improve the clinical progress of patients in intensive care; their use in common infections is not recommended. Ribavirin has been used in children with syncytial respiratory virus, and in immunosuppressed subjects. Apart from these drugs, no antiviral has been shown to be effective. Prevention with anti-influenza virus vaccination and with monoclonal antibodies, in the case of syncytial respiratory virus, may reduce the incidence of pneumonia.


title: Epidemiology of severe cases of influenza and other acute respiratory infections in the Eastern Mediterranean Region, July 2016 to June 2018

text: Abstract Background Influenza surveillance systems in the Eastern Mediterranean Region have been strengthened in the past few years and 16 of the 19 countries in the Region with functional influenza surveillance systems report their influenza data to the EMFLU Network. This study aimed to investigate the epidemiology of circulating influenza viruses, causing SARI, and reported to the EMFLU during July 2016 to June 2018. Methods Data included in this study were collected by 15 countries of the Region from 110 SARI sentinel surveillance sites over two influenza seasons. Results A total of 40,917 cases of SARI were included in the study. Most cases [20,551 (50.2%)] were less than 5years of age. Influenza virus was detected in 3995 patients, 2849 (11.8%) were influenza A and 1146 (4.8%) were influenza B. Influenza A(H1N1)pdm09 was the predominant circulating subtype with 1666 cases (58.5%). Other than influenza, respiratory syncytial virus was the most common respiratory infection circulating, with 277 cases (35.9%). Conclusion Influenza viruses cause a high number of severe respiratory infections in EMR. It is crucial for the countries to continue improving their influenza surveillance capacity in order detect any unusual influenza activity or new strain that may cause a pandemic.


title: Silencing Viral MicroRNA as a Novel Antiviral Therapy?

text: Viruses are intracellular parasites that ensure their existence by converting host cells into viral particle producing entities or into hiding places rendering the virus invisible to the host immune system. Some viruses may also survive by transforming the infected cell into an immortal tumour cell. MicroRNAs are small non-coding transcripts that function as posttranscriptional regulators of gene expression. Viruses encode miRNAs that regulate expression of both cellular and viral genes, and contribute to the pathogenic properties of viruses. Hence, neutralizing the action of viral miRNAs expression by complementary single-stranded oligonucleotides or so-called anti-miRNAs may represent a strategy to combat viral infections and viral-induced pathogenesis. This review describes the miRNAs encoded by human viruses, and discusses the possible therapeutic applications of anti-miRNAs against viral diseases.


title: Recycling of chloroquine and its hydroxyl analogue to face bacterial, fungal and viral infections in the 21st century

text: Abstract Chloroquine (CQ) and its hydroxyl analogue hydroxychloroquine (HCQ) are weak bases with a half-century long use as antimalarial agents. Apart from this antimalarial activity, CQ and HCQ have gained interest in the field of other infectious diseases. One of the most interesting mechanisms of action is that CQ leads to alkalinisation of acid vesicles that inhibit the growth of several intracellular bacteria and fungi. The proof of concept of this effect was first used to restore intracellular pH allowing antibiotic efficacy for Coxiella burnetii, the agent of Q fever, and doxycycline plus HCQ is now the reference treatment for chronic Q fever. There is also strong evidence of a similar effect in vitro against Tropheryma whipplei, the agent of Whipple's disease, and a clinical trial is in progress. Other bacteria and fungi multiply in an acidic environment and encouraging in vitro data suggest that this concept may be generalised for all intracellular organisms that multiply in an acidic environment. For viruses, CQ led to inhibition of uncoating and/or alteration of post-translational modifications of newly synthesised proteins, especially inhibition of glycosylation. These effects have been well described in vitro for many viruses, with human immunodeficiency virus (HIV) being the most studied. Preliminary in vivo clinical trials suggest that CQ alone or in combination with antiretroviral drugs might represent an interesting way to treat HIV infection. In conclusion, our review re-emphasises the paradigm that activities mediated by lysosomotropic agents may offer an interesting weapon to face present and future infectious diseases worldwide.


title: Excessive lysosomal ion-trapping of hydroxychloroquine and azithromycin

text: Abstract A recent report identified significant reductions or disappearance of viral load in COVID-19 patients given a combination of hydroxychloroquine and azithromycin. The present communication discusses some common pharmacokinetic properties of these two drugs that may be linked to a potential underlying mechanism of action for these antiviral effects. The physicochemical properties of both hydroxychloroquine and azithromycin are consistent with particularly high affinity for the intracellular lysosomal space, which has been implicated as a target site for antiviral activity. The properties of both drugs predict dramatic accumulation in lysosomes, with calculated lysosomal drug concentrations that exceed cytosolic and extracellular concentrations by more than 50 000-fold. These predictions are consistent with previously reported experimentally measured cellular and extracellular concentrations of azithromycin. This is also reflected in the very large volumes of distribution of these drugs, which are among the highest of all drugs currently in use. The combination of hydroxychloroquine and azithromycin produces very high local concentrations in lysosomes. The clinical significance of this observation is unclear; however, the magnitude of this mechanism of drug accumulation via ion-trapping in lysosomes could be an important factor for the pharmacodynamic effects of this drug combination.


title: Health Promoting Schools: An Update

text: The concept of a Health Promoting School has been found to be effective to improve health and well-being of students as well as a help with teaching and learning in school. Effective implementation of Health Promoting School is a complex intervention involving multi-factorial and innovative activity in many domains such as curriculum, school environment and community. Many studies evaluating Health Promoting School do not include outcomes reflecting the organisational or structural change as many of those studies are quantitative in nature and the statistical assumptions are not valid reflecting the organisational structure changes. Recent global meetings of experts have reviewed the impact on student health from the perspectives of school environment, school policies on health, action competencies on healthy living and community linkage. The English Wessex Healthy School Award Scheme and the Hong Kong Healthy School Awards Scheme have developed detailed systems to analyse whether each individual school has reached the standard of a model Health Promoting School reflecting a more holistic appreciation and understanding of all the effects of school-based health promotion with positive award-related changes. However, not many schools are able to implement Health Promoting School in its entirety, so cores indicators are needed as a starting point for wider implementation. Hong Kong Healthy School Awards Scheme is still ongoing with data for analysis of indicators with significant correlation with better health and well-being. We identified the core indicators and substantiated the requirements for successful outcomes by supplementing the established award-scheme framework with a review of recent literature and documents. Framework of Health Promoting School would go beyond improvement of health literacy to enable a more efficient system for education and health on children, hence a good investment in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40258-020-00575-8) contains supplementary material, which is available to authorized users.


title: Unique Challenges to Control the Spread of COVID-19 in the Middle East

text: The COVID-19 pandemic is spreading at unprecedented pace among the Middle East and neighboring countries. This region is geographically, economically, politically, culturally and religiously a very sensitive area, which impose unique challenges for effective control of this epidemic. These challenges include compromised healthcare systems, prolonged regional conflicts and humanitarian crises, suboptimal levels of transparency and cooperation, and frequent religious gatherings. These factors are interrelated and collectively determine the response to the pandemic in this region. Here, we in-depth emphasize these challenges and take a glimpse of possible solutions towards mitigating the spread of COVID-19.


title: Reservoir bats: The invisible enemy

text: We're discovering hordes of potentially lethal viruses lurking in bats, which are occasionally jumping into people. Is there anything we can do about it?


title: Common WU polyomavirus infection in a Beijing population indicated by surveillance for serum IgG antibody against capsid protein VP2

text: BACKGROUND: WU polyomavirus (WU virus) was identified as a novel polyomavirus in 2007 from specimens of pediatric patients with acute respiratory infection (ARI). A lack of permissive cell lines has limited investigations into WU virus pathogenesis and prevalence. METHODS: The encoding region of the capsid protein VP2 gene was amplified from a WU virus DNA-positive clinical specimen and expressed as a recombinant Histagged protein in Escherichia coli BL21 (DE3). The expressed VP2 was identified by expected molecular weight and immunoreactivity with anti-His monoclonal antibody in Western blotting assay. Serum samples collected from 455 individuals of all ages in Beijing without symptoms of ARI were tested for IgG antibodies against the affinity-purified recombinant VP2 protein by Western blotting to investigate the prevalence of natural WU virus infection. In addition, serum samples from four ARI pediatric patients, whose nasopharyngeal aspirates were positive for WU virus DNA and negative for all other respiratory-related viruses, were tested for IgM antibody against the recombinant VP2. RESULTS: Of the 455 serum samples, 238 reacted with the recombinant VP2, yielding an overall positive rate of 52.3% for IgG against VP2 of WU virus. The positive rate was the highest in serum samples from infants and children between 1 to 4 years of age. One of four ARI pediatric patients was positive for IgM against WU virus VP2, implicating WU virus as the causative disease agent. CONCLUSIONS: The high prevalence of IgG against WU polyomavirus in Beijing-based study population indicates that WU virus infection is common in Beijing. WU virus may be responsible for some pediatric ARI cases, and primary infection of this virus may occur mostly in childhood.


title: Examining Social Determinants of Health, Stigma, and COVID-19 Disparities

text: There is growing attention to disparities in the incidence, prevalence, and mortality associated with COVID-19 (Coronavirus disease 2019) in racial/ethnic communities. The conditions leading to these disparities may be a function of social determinants of health and stigma linked to the disease. It is important to examine how these factors may be implicated in COVID-19 onset, treatment, and outcomes. A brief overview of these issues allows for a cursory examination of the role of social determinants of health and stigma in COVID-19. Consideration is given to how understanding COVID-19 in the context of social determinants and stigma may be included in interventions to mitigate its transmission within vulnerable populations.


title: Keep your (social) distance: Pathogen concerns and social perception in the time of COVID-19

text: Previous research suggests that individual differences in pathogen disgust sensitivity and social anxiety predict avoidance behavior, especially of pathogen cues, and reduced tolerance for social ambiguity. Conversely, generalized social trust is associated with approach behavior and a greater tolerance for social ambiguity. We conducted an online study (N = 1078) to test these predictions in the context of the COVID-19 global pandemic. Specifically, we assessed whether individual differences in pathogen disgust sensitivity, social anxiety and generalized social trust predicted judgments of trustworthiness, desired social distance and perceptions of sickness of target faces wearing surgical masks. Our results showed that (a) high sensitivity to pathogen disgust predicted lower judgments of trustworthiness and lower social desirability; (b) high social anxiety predicted higher perceptions of illness and lower judgments of trustworthiness; and (c) generalized social trust predicted higher judgments of trustworthiness and lower perceptions of illness of target faces. Further, we found that mask wearers were perceived as more likely to be ill, more trustworthy and more socially desirable than the same faces presented to a control group, without the surgical mask superimposed. Results are discussed in terms of perceived compliance with an emerging social norm overriding the intrinsic mistrustfulness of masked faces.