title: Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

text: Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children.


title: Three‐dimensional model of a substrate‐bound SARS chymotrypsin‐like cysteine proteinase predicted by multiple molecular dynamics simulations: Catalytic efficiency regulated by substrate binding

text: Severe acute respiratory syndrome (SARS) is a contagious and deadly disease caused by a new coronavirus. The protein sequence of the chymotrypsin‐like cysteine proteinase (CCP) responsible for SARS viral replication has been identified as a target for developing anti‐SARS drugs. Here, I report the ATVRLQ(p1)A(p1')‐bound CCP 3D model predicted by 420 different molecular dynamics simulations (2.0 ns for each simulation with a 1.0‐fs time step). This theoretical model was released at the Protein Data Bank (PDB; code: 1P76) before the release of the first X‐ray structure of CCP (PDB code: 1Q2W). In contrast to the catalytic dyad observed in X‐ray structures of CCP and other coronavirus cysteine proteinases, a catalytic triad comprising Asp187, His41, and Cys145 is found in the theoretical model of the substrate‐bound CCP. The simulations of the CCP complex suggest that substrate binding leads to the displacement of a water molecule entrapped by Asp187 and His41, thus converting the dyad to a more efficient catalytic triad. The CCP complex structure has an expanded active‐site pocket that is useful for anti‐SARS drug design. In addition, this work demonstrates that multiple molecular dynamics simulations are effective in correcting errors that result from low‐sequence‐identity homology modeling. Proteins 2004. © 2004 Wiley‐Liss, Inc.


title: Primum non nocere – Are chloroquine and hydroxychloroquine safe prophylactic/treatment options for SARS-CoV-2 (covid-19)?

text: Chloroquine (CQ) and its analog hydroxychloroquine (HCQ) were recently included in several clinical trials as potential prophylactic and therapeutic options for SARS-COV-2 infection/covid-19. However, drug effectiveness in preventing, treating, or slowing the progression of the disease is still unknown. Despite some initial promising in vitro results, rigorous pre-clinical animal studies and randomized clinical trials have not been performed yet. On the other hand, while the potential effectiveness of CQ/HCQ is, at best, hypothetical, their side effects are factual and most worrisome, particularly when considering vulnerable groups of patients being treated with these drugs. in this comment, we briefly explain the possible mechanisms of action of CQ/HCQ for treating other diseases, possible actions against covid-19, and their potent side effects, in order to reinforce the necessity of evaluating the benefit-risk balance when widely prescribing these drugs for SARS-COV-2 infection/covid-19. We conclude by strongly recommending against their indiscriminate use.


Ivermectina en COVID-19. ¿Argumentum ad ignorantiam?


title: Acute disseminated encephalomyelitis associated with hepatitis B virus reinfection – Consequence or coincidence?

text: Abstract Acute disseminated encephalomyelitis (ADEM) is an idiopathic inflammatory demyelinating disease of the CNS that is particularly difficult to differentiate from the first episode of multiple sclerosis. ADEM typically occurs as a post-infectious phenomenon, and usually presents a monophasic episode, but also includes recurrent and multiphasic forms. We report a case of ADEM associated with hepatitis B virus (HBV) reinfection. After steroid and IV immunoglobulin treatment, neurologic symptoms were improved. We suppose that the HBV reinfection was the cause of ADEM, but possible pathogenetic mechanism is still obscure.


title: The ALPHA Project: An architecture for leveraging public health applications

text: Summary Objective Public health surveillance applications are central to the collection, analysis and dissemination of disease and health information. As these applications evolve and mature, it is evident that many of these applications must address similar requirements, such as policies, security and flexibility. It is important a software architecture is created to meet these requirements. Methods We outline the requirements for a public health surveillance application, and define a set of common components to address these requirements. These components are configured to produce services used in the development of public health applications. Results A layered software architecture, the ALPHA architecture, has been developed to support the development of public health applications. The architecture has been used to build eleven surveillance applications for the Public Health Agency of Canada in the areas of disease surveillance, survey, distributed data collection and inventory management. Conclusions We have found that a software architecture that addresses requirements on policies, security and flexibility facilitates the development of configurable public health applications. By creating this architecture, key success factors, such as reducing cost and time-to-market of applications, adapting to changing surveillance targets and increasing user efficiency are achieved.


title: B-Cell-Mediated Lysis of Cells Infected with the Neurotropic JHM Strain of Mouse Hepatitis Virus

text: Abstract Cells expressing the spike (S) glycoprotein of the neurotropic JHM strain (JHMV) of mouse hepatitis virus (MHV) are susceptible to lysis by B cells derived from naı̈ve mice, including B cells from perforin-deficient mice. Cytolysis requires interaction of the virus receptor and the viral S glycoprotein, is independent of other viral-induced components, and is not a unique property of B cells. Neutralizing anti-S-protein monoclonal antibodies (mAb) and a mAb specific for the viral receptor inhibit lysis. However, cells infected with an MHV strain unable to induce cell–cell fusion are resistant to lysis and lysis of JHMV-infected cells is inhibited by an anti-S-protein nonneutralizing mAb which prevents S-protein-mediated cell fusion. These data suggest that B cells may function as antibody-independent innate immune response during JHMV infection in vivo.


title: Effectiveness of the 2010–2011 seasonal influenza vaccine in preventing confirmed influenza hospitalizations in adults: A case–case comparison, case-control study

text: INTRODUCTION: We estimated influenza vaccine effectiveness (IVE) to prevent laboratory-confirmed influenza-related hospitalizations in patients 18 years old or older during the 2010–2011 influenza season. METHODS: We conducted a prospective case-control study in five hospitals, in Valencia, Spain. Study subjects were consecutive emergency hospitalizations for predefined conditions associated with an influenza-like illness episode <8 days before admission. Patients were considered immunized if vaccinated ≥14 days before influenza-like illness onset. Cases were those with a real time reverse transcriptase polymerase chain reaction (RT-PCR) positive for influenza and controls were RT-PCR positive for other respiratory viruses. Adjusted IVE was estimated as 100 × (1 − adjusted odds ratio). To account for indication bias we computed adjusted IVE for respiratory syncytial virus related hospitalizations. RESULTS: Of 826 eligible hospitalized patients, 102 (12%) were influenza positive and considered cases, and 116 (14%) were positive for other respiratory viruses and considered controls. Adjusted IVE was 54% (95% confidence interval, 11–76%). By subgroup, adjusted IVE was 53% (4–77%) for those with high-risk conditions, 59% (16–79%) for those ≥60 years of age, and, 54% (4–79%) for those ≥60 years of age with high-risk conditions. No influenza vaccine effect was observed against respiratory syncytial virus related hospitalization. CONCLUSION: Influenza vaccination was associated with a significant reduction on the risk of confirmed influenza hospitalization, irrespective of age and high-risk conditions.


title: Perspectives towards antiviral drug discovery against Ebola virus

text: Ebola virus disease (EVD), caused by Ebola viruses, resulted in more than 11 500 deaths according to a recent 2018 WHO report. With mortality rates up to 90%, it is nowadays one of the most deadly infectious diseases. However, no Food and Drug Administration‐approved Ebola drugs or vaccines are available yet with the mainstay of therapy being supportive care. The high fatality rate and absence of effective treatment or vaccination make Ebola virus a category‐A biothreat pathogen. Fortunately, a series of investigational countermeasures have been developed to control and prevent this global threat. This review summarizes the recent therapeutic advances and ongoing research progress from research and development to clinical trials in the development of small‐molecule antiviral drugs, small‐interference RNA molecules, phosphorodiamidate morpholino oligomers, full‐length monoclonal antibodies, and vaccines. Moreover, difficulties are highlighted in the search for effective countermeasures against EVD with additional focus on the interplay between available in silico prediction methods and their evidenced potential in antiviral drug discovery.


title: Molecular basis of COVID-19 relationships in different species: a one health perspective

text: Abstract Outside the Hubei province, China, the mild form of infection and the progressive recover of the COVID-19 patients suggest the intervention of “unconventional” biological mechanisms worthy of attention. Based on the high-homology between the Spike protein epitopes of taxonomically-related coronaviruses, we hypothesized that past contact with infected dogs shield humans against the circulating SARS-CoV-2. Elseways, the recurrent virus exposure over a short time-lapse might result in the Antibody Dependent Enhancement, triggering the violent immune reaction responsible for the severe clinical outcomes observed in the Hubei province. Nevertheless, further experimental studies are desired for a confidential evaluation of the postulated hypotheses.


title: Dual infections of feeder pigs with porcine reproductive and respiratory syndrome virus followed by porcine respiratory coronavirus or swine influenza virus: a clinical and virological study

text: Abstract Dual infections of pigs with porcine reproductive and respiratory syndrome virus (PRRSV) followed by a second common respiratory virus, either porcine respiratory coronavirus (PRCV) or swine influenza virus (SIV), were studied. The aim was to determine if dual infections, as compared to single virus infections, result in enhanced clinical manifestations. It was also examined if PRRSV replication affects replication of PRCV or SIV in the respiratory tract. Groups of conventional 10 week old pigs were inoculated with PRRSV-only (3 pigs), PRCV-only (4 pigs) or SIV-only (4 pigs). Dual inoculations with PRRSV-PRCV (4 pigs) and PRRSV-SIV (3 groups of 4, 4 and 5 pigs) were performed at a 3 day interval. A group of uninoculated control pigs (8 pigs) was included. The infection with PRRSV-only induced a transient fever (40.2°C) at 2 DPI, but no respiratory signs. The PRCV-only infection remained subclinical. The SIV-only infection resulted in a one day fever (40.1°C) with moderate tachypnoea and dyspnoea. Mean weight gain in the virus-inoculated groups was retarded compared with the control group. The PRRSV-PRCV infection induced a 9 day lasting fever (peak 40.9°C) with tachypnoea, dyspnoea and productive coughing. The PRRSV-SIV infection resulted in fever and respiratory signs in all 3 groups. Clinical signs, however, were more pronounced in group 1 than in groups 2 and 3. Pigs of group 1 showed fever during 10 days (peak 41.4°C), tachypnoea, marked dyspnoea with abdominal breathing, and a productive cough. Pigs of groups 2 and 3 had fever for 5 and 3 days (peaks 40.6 and 40.3°C) respectively and mild respiratory disorders. Mean weight gain during 14 DPI of the 2nd virus was 5.9 kg in the PRRSV-PRCV group and 4.0, 6.8 and 6.7 kg in PRRSV-SIV groups 1, 2 and 3 respectively. Mean weight gain during the corresponding period in the PRRSV-only group was 8.6 kg. It was concluded that dual infections with viruses causes more severe disease and growth retardation than single PRRSV infection. PRCV excretion curves were similar in single and dual virus inoculated groups. Excretion of SIV was delayed by 2 days in the dual inoculated pigs. Thus, replication of the second virus is not (PRCV) or only slightly (SIV) affected by a prior infection with PRRSV.


title: Sequence analysis of strains of avian infectious bronchitis coronavirus isolated during the 1960s in the U.K.

text: Sequencing of parts of the spike, small membrane, and integral membrane protein genes of English isolates of avian infectious bronchitis virus (IBV) isolated in the 1960s revealed that they were not the direct ancestors of those isolated in the 1980s.


Analysis of SARS-CoV Receptor Activity of ACE2 Orthologs


title: Efficacy of a Dried Colostrum Powder in the Prevention of Disease in Neonatal Holstein Calves

text: Abstract The efficacy of a dried colostrum powder, DCW Concentrate™, as a colostrum supplement or substitute was tested using four groups of 15 calves. Physical condition and IgG status were examined during the first 30 d of life. Calves were fed the dried colostrum powder (group A), pooled colostrum (group C), or both (groups B and D) 2h after birth. Calves fed 85g of the dried colostrum powder dissolved in 3kg of whole milk (group A) had significantly lower IgG concentrations 24h after birth than calves of the other groups. Administration of 85g of the dried colostrum powder plus 3kg of colostrum (group C) did not lead to significantly higher IgG concentrations 24h after birth than did administration of 3kg of colostrum alone (group B). Calves fed 85g of the dried colostrum powder plus 1.5kg of colostrum (group D) had an IgG concentration at 24h of age that was not significantly different from that of calves given 3kg of colostrum (group B). Morbidity and mortality rates were not significantly different among groups. One calf died in each of groups A and B; no losses occurred in groups C and D. Body weight increase was not significantly different among groups.


title: Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection: How Close Are We?

text: Over 1100 cases of MERS-CoV have been reported since it was first identified in June 2012. Clinical presentation ranges from asymptomatic or mild illness to rapidly progressive disease with multi-organ failure and high mortality. Treatment has been largely supportive. A large number of compounds have been shown to have significant in vitro inhibitory activity against MERS-CoV. Until recently, macaques were the only suitable animal models for animal studies, hindering further clinical development of MERS-CoV therapy. However, the recent successful development of MERS-CoV infection model in transduced mice offers opportunities to accelerate clinical development of therapeutic agents for MERS-CoV infection. Currently available evidence supports further clinical investigation of interferon-based treatment regimens for patients with MERS-CoV. Combining interferon with mycophenolate and/or high-dose ribavirin appears especially promising. Monoclonal antibodies against various targets within MERS-CoV Spike protein have yielded encouraging in-vitro results. However, their safety and efficacy require confirmation in animal models and exploratory clinical trials.


SARS-CoV-2 infection in very preterm pregnancy: experiences from two cases


title: Predictors of hand hygiene practice among Saudi nursing students: A cross-sectional self-reported study

text: Summary Hand hygiene is an important component of infection control, which is critical to ensuring patients’ safety in hospitals. Nursing students are regarded as healthcare workers in training and can also be vehicles of cross-contamination within the hospital. Thus, this study aimed to identify the predictors of hand hygiene practice among Saudi nursing students. A descriptive, cross-sectional, self-reported study was conducted among 198 Saudi nursing students. Knowledge, attitude, and practice of hand hygiene were assessed using the WHO Hand Hygiene Knowledge Questionnaire for Health-Care Workers and its adopted scales. A regression analysis was performed to identify the predictors of hand hygiene practice. The respondents demonstrated moderate knowledge of hand hygiene (mean 13.20±2.80). The majority displayed a moderate attitude toward hand hygiene (52.1%), while only a few reported a poor attitude (13.1%). Approximately 68.7%, 29.8%, and 1.5% of the respondents reported moderate, good, and poor practice of hand hygiene, respectively. Having a good attitude toward hand hygiene, being male, being aware that hand hygiene is an effective intervention in preventing healthcare-associated infections (HAIs), attendance at hand hygiene trainings and seminars, and being in the lower academic level of nursing education were identified as predictors of better hand hygiene practice. The importance of ensuring a positive attitude toward hand hygiene and improving awareness of hand hygiene is emphasized, as are educational interventions. Educational interventions should be implemented to reinforce knowledge and instill a positive attitude toward hand hygiene.


title: Studies on the evolution, pathology, and immunity of commercial fattening rabbits affected with epizootic outbreaks of diarrhoeas in Mexico: A case report

text: Abstract Epizootic outbreaks of diarrhoeas have emerged and disseminated in different rabbit farms in Mexico causing great economical losses, during the past years. Seven, 5-weeks-old New Zealand White (NZW) rabbits chosen at random from 35 ill animals that were remitted for postmortem, histopathology, and ultrastructural examinations were studied. Bacteriological and parasitological studies were carried out in three additional ill rabbits of same age. In a field trail 45, 5-weeks-old apparently healthy NZW rabbits were observed daily for sanitary status for a 5-week period. Some of the rabbits did not response to the preventive drug treatment and were therefore, used to study the development of the disease. Clinical signs, gross lesions, and mortality throughout the fattening period were recorded. Eight, 8-weeks-old NZW rabbits who survived an outbreak were assessed for gamma-globulins in serum of the total protein fraction during a 3-week period. Gamma-globulins were also measured in eight free-disease healthy rabbits of same breed and age. Lesions of the small intestine consisted of mucoid enteropathy, lymphocytic plasmocytic enteritis with atrophy and fusion of villi, and hyperplasia of globet cells. Serosal edema was present. Ultrastructural examinations of jejunum and ileum from 3/7 diseased rabbits, revealed enterocytes in apoptosis, mixed with degenerative and/or necrotic changes together with infiltration of lymphocytes, macrophages, neutrophils, and loss of microvillus. There were electron dense structures suggestive of virus particles inside the nuclei and cytoplasm of some enterocytes. There was lymphoid spleen atrophy and proliferation of reticuloendothelial cells in 7/7 rabbits. Interstitial pneumonia in 4/7 rabbits was found. Encephalitozoon cuniculi was detected in the brain of 1/7 rabbits. Escherichia coli were detected in 3/3 cases and Eimeria spp. in 2/3 cases. Mortality rate in the field study was 51.1% and the spread of the disease occur in 9/9 cages. The proportion of gamma-globulins in rabbits who survive an outbreak was much lower (P =0.0001) than free-disease healthy rabbits (8.1±1.0 and 14.0±1.0, respectively). The disease was multifactorial and consisted of sub-acute mucoid enteropathy probably induced by viral infection and aggravated by the proliferation of opportunistic pathogens common to rabbits. This may explain the severe degenerative and necrotic changes observed in the small intestine of diarrhoeic rabbits.


title: Stimulatory role of interleukin 10 in CD8(+) T cells through STATs in gastric cancer

text: CD8(+) T cells are considered to be critical in tumor surveillance and elimination. Increased CD8(+) T cell frequency and function is associated with better prognosis in cancer patients. Interleukin 10 is a cytokine with controversial roles in CD8(+) T cell–mediated anti-tumor immunity. We therefore examined the interleukin 10 expression and consumption in CD8(+) T cells harvested from the peripheral blood and resected tumors of gastric cancer patients of stages II–IV. We found that the gastric cancer patients presented significantly elevated frequencies of interleukin 10–expressing cells in both CD4(+) and CD8(+) T cells compared to healthy controls. But distinctive from the interleukin 10–expressing CD4(+) T cells, which increased in frequency in advanced cancer, the interleukin 10–expressing CD8(+) T cells did not increase with cancer stage in the peripheral blood and actually decreased with cancer stage in resected tumor. Interleukin 10 and interleukin 10 receptor expression was also enriched in interferon gamma–expressing activated CD8(+) T cells. Compared to interleukin 10–nonexpressing CD8(+) T cells, interleukin 10 receptor–expressing CD8(+) T cells secreted significantly elevated interferon gamma levels. Treatment of anti-CD3/CD28-stimulated, purified CD8(+) T cells with interleukin 10 alone could significantly enhance CD8(+) T cell survival, an effect dependent on interleukin 10 receptor expression. Interleukin 10 also increased CD8(+) T cell proliferation synergistically with interferon gamma but not alone. Analysis of downstream signal transducer and activator of transcription molecules showed that interleukin 10 treatment significantly increased the phosphorylation of signal transducer and activator of transcription 3 and signal transducer and activator of transcription 1 to lesser extent. Together, these results demonstrate that interleukin 10 possessed stimulatory roles in activated CD8(+) T cells from gastric cancer patients.


title: Replication of bovine coronavirus in cell line BEK-1 culture

text: Bovine coronavirus readily multiplied and induced marked cytopathic effect in BEK-1 cultures, thus providing a sensitive, practical assay system for viral infectivity and neutralizing antibody and a satisfactory source of the virus.


title: Targeted Strategies for Henipavirus Therapeutics

text: Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds.


title: The nucleotide sequence of the peplomer gene of porcine transmissible gastroenteritis virus (TGEV): comparison with the sequence of the peplomer protein of feline infectious peritonitis virus (FIPV)

text: Abstract The amino acid sequence of the peplomer protein of transmissible gastroenteritis virus (TGEV) has been derived from the cloned cDNA sequence. The gene encodes a protein of 1447 amino acids with a molecular weight of 159 574. Comparison with the primary structure of the peplomer protein of feline infectious peritonitis virus (FIPV) (de Groot et al., 1987b) revealed one domain, from amino acids 1 to 274, in which the nucleotide homology was 39%, whereas in the second domain (from residues 275 to 1447) the homology was 93%.


title: Attenuation of SARS coronavirus by a short hairpin RNA expression plasmid targeting RNA-dependent RNA polymerase

text: Abstract Severe acute respiratory syndrome (SARS) is a highly contagious and sometimes a lethal disease, which spread over five continents in 2002–2003. Laboratory analysis showed that the etiologic agent for SARS is a new type of coronavirus. Currently, there is no specific treatment for this disease. RNA interference (RNAi) is a recently discovered antiviral mechanism in plant and animal cells that induces a specific degradation of double-stranded RNA. Here, we provide evidences that RNAi targeting at coronavirus RNA-dependent RNA polymerase (RDRP) using short hairpin RNA (shRNA) expression plasmids can specifically inhibit expression of extraneous coronavirus RDRP in 293 and HeLa cells. Moreover, this construct significantly reduced the plaque formation of SARS coronaviruses in Vero-E6 cells. The data may suggest a new approach for treatment of SARS patients.


Powerless in the ICU: Perspectives from Intensive Care Units in the Face of COVID-19.


title: Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) associated stress among medical students at a university teaching hospital in Saudi Arabia

text: Abstract Background and objectives Middle East Respiratory Syndrome Corona Virus (MERS-CoV) outbreak in 2014 was associated with high public anxiety in the affected countries. Media speculations may have increased this psychological distress. The healthcare community was the most distressed because they were at the highest risk of infection. This study is the first to explore MERS-CoV epidemic impact on medical students’ perception and determinants of their psychological distress during this outbreak. Methods We randomly selected and surveyed 200 students from the College of Medicine at King Saud University, Riyadh, Saudi Arabia. A predesigned questionnaire was answered by participants, and the collected data were statistically analyzed. Results One hundred and seventy-four (87%) responded. Female students had a significantly higher mean stress level than males (P < 0.001). Participants had a mean GAD score of 2.7 ± 3.1 and a median of 2. Perceived sufficiency of information score was the highest mean and median (17.4 ± 4.2 and 18 respectively). College and hospital announcements were the most common source of information (25.4%). One hundred and thirty-four (77%) reported minimal anxiety, thirty-two (18.4%) reported mild anxiety, 8 (4.6%) reported moderate anxiety, and none of them reported severe anxiety (score >14). The stress level (as reported on 1–10 scale) shows significant correlation with Generalized Anxiety Disorder (GAD-7) score. We found in this study that significant predictors in our model, in terms of more significant to the least, were: an increased self-report on hygienic habits, self-reported social avoidance, the generalized anxiety score and finally being female gander while other variables including numbers of resources access, agreeing with public fear and knowledge score on MERS-CoV all were found to be non-significant. However, the number of accessed resources, as per students, has borderline significant correlation with higher self-reported anxiety from MERS-CoV. Conclusions Medical students’ psychological needs during the MERS-CoV outbreak should be addressed appropriately. Our results highlight the need to establish psychological support programs for medical students during an infectious disease outbreak.


title: Demand for Health Information on COVID-19 among Vietnamese

text: Due to the rapid spread of coronavirus, Vietnam introduced its first national partial lockdown on April 1st, 2020. The public relied on online sources, whether through official websites or phone-based applications, to acquire up-to-date health information, provide accurate instructions, and limit misinformation. This study aims to provide insight regarding the current level of awareness of the pandemic, and to identify associated factors in Vietnamese participants to recommend necessary interventions. A cross-sectional study was conducted using a web-based survey during the first week of the lockdown period. There were 341 observations collected using a snowball sampling technique. A Tobit multivariable regression model was used to identify factors associated with the demand for each category of health information. The most requested information was the latest updated news on the epidemic, followed by information about disease symptoms and updated news on the outbreak. The prevalence of diverse socioeconomic, demographic, and ethnic factors in Vietnam requires consideration of the specific health information needs of unique groups. Identifying group-specific demands would be helpful to provide proper information to fulfill each population group’s needs.


title: Comparable humoral response after two doses of adjuvanted influenza A/H1N1pdm2009 vaccine or natural infection in allogeneic stem cell transplant recipients

text: BACKGROUND: The present study evaluated immunogenicity and tolerance of two-dose influenza A/H1N1pdm09 vaccination in allogeneic hematopoietic stem cell transplantation (HSCT) recipients, and compared the vaccine-induced humoral response to that triggered by natural infection in another group of HSCT patients. METHODS: Adult allogeneic HSCT recipients vaccinated with two doses of influenza A/H1N1pdm09 vaccine, separated by 3 weeks, and patients with proven influenza A/H1N1pdm09 infection were included. Antibody responses were measured by hemagglutination-inhibition assay 1) on days 0, 21, 42 and 6 months after the first vaccine injection in vaccinated patients and 2) before pandemic and after influenza A/H1N1pdm09 infection, in patients presented natural infection. RESULTS: At baseline, 3% of 59 recipients of adjuvanted vaccine and 0% of 20 infected patients were seroprotected (antibody titer ≥ 1/40). Seroprotection rate observed 42 days after vaccination was not different from that observed after natural infection (66% and 60% respectively, p = 0.78). In vaccinated patients, seroprotection rate increased significantly from 54% to 66% between day 21 and 42 (p = 0.015). Moreover, after 6 months, seroprotection rate in 21 vaccinated patients was similar to that observed in 10 infected patients evaluated at least 76 days after infection (D76–217) (60% and 81% respectively, p = 0.2). In multivariate analysis, no immunosuppressive treatment or chronic graft-versus-host disease (GVHD) and longer time between transplantation and vaccination/infection were associated with a stronger humoral response. The adjuvanted vaccine was safe with low rate of GVHD worsening. CONCLUSION: In HSCT recipients, two doses of influenza A/H1N1pdm09 adjuvanted vaccine were safe and induced a humoral response comparable to that triggered by natural infection in these patients.


title: COVID-19: Four Paediatric Cases in Malaysia

text: Abstract Objective This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia Background COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. Cases In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. Discussion There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.


The importance of IL-6 blockade beyond the COVID-19 pandemic: consideration for cancer care


title: Etiology of community-acquired pneumonia in hospitalized children based on WHO clinical guidelines

text: Community-acquired pneumonia (CAP) is a major cause of death in developing countries and of morbidity in developed countries. The objective of the study was to define the causative agents among children hospitalized for CAP defined by WHO guidelines and to correlate etiology with clinical severity and surrogate markers. Investigations included an extensive etiological workup. A potential causative agent was detected in 86% of the 99 enrolled patients, with evidence of bacterial (53%), viral (67%), and mixed (33%) infections. Streptococcus pneumoniae was accounted for in 46% of CAP. Dehydration was the only clinical sign associated with bacterial pneumonia. CRP and PCT were significantly higher in bacterial infections. Increasing the number of diagnostic tests identifies potential causes of CAP in up to 86% of children, indicating a high prevalence of viruses and frequent co-infections. The high proportion of pneumococcal infections re-emphasizes the importance of pneumococcal immunization.


title: Stress hormones bring birds, pathogens and mosquitoes together

text: Do stress hormones such as corticosterone enhance bird susceptibility to mosquitoes in ways that enhance rates of coinfection? Does this then enhance pathogen emergence?


title: ESMO management and treatment adapted recommendations in the COVID-19 era: colorectal cancer

text: COVID-19 pandemic challenges health system capacities in many countries. National healthcare services have to manage unexpected shortage of healthcare resources that have to be reallocated according to the principles of fair and ethical prioritisation, in order to maintain the highest levels of care to all patients, ensure the safety of patients and healthcare workers and save as many lives as possible. Beyond that, cancer care services have to pursue restructuring, following the same evidence-based dispositions. In this article, we propose guidance to the management of colorectal cancer during the pandemic, prioritised according to a three-tiered framework, based on expert clinical judgement and magnitude of benefit expected from specific interventions. Since the availability of resources for diagnostic procedures, surgery and postoperative care, systemic therapy and radiotherapy may differ, authors did separate prioritisation analyses. The impact of postponing or abrogating cancer interventions on outcomes according to a high, medium or low priority scale, is outlined and discussed. The implementation of healthcare services using telemedicine is explored: it reveals itself as functional and effective for limiting patients’ need to travel to centres and thereby has the potential to reduce diffusion of severe acute respiratory syndrome coronavirus 2. Colorectal cancer demands a considerable amount of medical resources. Therefore, the redefinition of its diagnostic and therapeutic algorithms with a rigorous method is crucial in order to ensure the highest quality of continuum of care in the broader context of the pandemic and the challenged healthcare systems.


title: The Politics of Disease Epidemics: a Comparative Analysis of the SARS, Zika, and Ebola Outbreaks

text: Over the past few decades, disease outbreaks have become increasingly frequent and widespread. The epicenters of these outbreaks have differed, and could be linked to different economic contexts. Arguably, the responses to these outbreaks have been “political” and inherently burdensome to marginalized populations. Key lessons can be learned from exploring the narratives about the different epidemics in varying income settings. Based on a review of the published medical, social, and political literature, which was accessed using four electronic databases—PubMed, Sociological Abstracts, Scholars Portal, and Web of Science, the overall objective of this paper discuss scholars’ narratives on the “politics” of Ebola in a low-income setting, Zika virus in a middle-income setting, and SARS in a high-income setting. Various themes of the politics of epidemics were prominent in the literature. The narratives demonstrated the influence of power in whose narratives and what narratives are presented in the literature. While marginalized populations were reported to have borne the brunt of all disease outbreaks in the different contexts, the prevalence of their narratives within the reviewed literature was limited. Regardless of income setting, there is a need to give voice to the most marginalized communities during an epidemic. The experiences and narratives of those most vulnerable to an epidemic—specifically poor communities—need to be represented in the literature. This could contribute to mitigating some of the negative impact of the politics in epidemics.


Transforming Schools into Pre-designed Alternative Care Sites as Part of Preparedness Plan for Pandemic H5N1 Influenza


title: A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles

text: Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV cannot bind to viper NPC1. This resistance to infection can be mapped to a single amino acid residue in viper NPC1 that renders it unable to bind to EBOV GP. The newly solved structure of EBOV GP bound to NPC1 confirms our findings, revealing that this residue dips into the GP receptor-binding pocket and is therefore critical to the binding interface. Consequently, this otherwise well-conserved residue in vertebrate species influences the ability of reptilian NPC1 proteins to bind to EBOV GP, thereby affecting viral host range in reptilian cells.


title: Intravenous Hypertonic Saline Solution (7.5%) and Oral Electrolytes to Treat of Calves with Noninfectious Diarrhea and Metabolic Acidosis

text: OBJECTIVE: The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). EXPERIMENTAL DESIGN: Eighteen male calves 8–30 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution‐HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post‐induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. RESULTS: Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post‐treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES‐treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post‐treatment. CONCLUSION: Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration.


Earth Day Reflections: Hope Amid the Pandemic


title: The potential impact of vulnerability and coping capacity on the pandemic control of COVID-19

text: • The European commission has developed an index for risk management named INFORM; • Two dimensions (vulnerability and lack of coping capacity) are relevant to COVID-19; • We examined if these dimensions were associated with COVID-19 pandemic control; • Higher vulnerability and poorer coping capacity were associated with poorer control; • Modifying these two dimensions might potentially mitigate COVID-19 pandemic control.


title: Biosensors and rapid diagnostic tests on the frontier between analytical and clinical chemistry for biomolecular diagnosis of dengue disease: A review

text: Abstract The past decades have witnessed enormous technological improvements towards the development of simple, cost-effective and accurate rapid diagnostic tests for detection and identification of infectious pathogens. Among them is dengue virus, the etiologic agent of the mosquito-borne dengue disease, one of the most important emerging infectious pathologies of nowadays. Dengue fever may cause potentially deadly hemorrhagic symptoms and is endemic in the tropical and sub-tropical world, being also a serious threat to temperate countries in the developed world. Effective diagnostics for dengue should be able to discriminate among the four antigenically related dengue serotypes and fulfill the requirements for successful decentralized (point-of-care) testing in the harsh environmental conditions found in most tropical regions. The accurate identification of circulating serotypes is crucial for the successful implementation of vector control programs based on reliable epidemiological predictions. This paper briefly summarizes the limitations of the main conventional techniques for biomolecular diagnosis of dengue disease and critically reviews some of the most relevant biosensors and rapid diagnostic tests developed, implemented and reported so far for point-of-care testing of dengue infections. The invaluable contributions of microfluidics and nanotechnology encompass the whole paper, while evaluation concerns of rapid diagnostic tests and foreseen technological improvements in this field are also overviewed for the diagnosis of dengue and other infectious and tropical diseases as well.


title: Changes in liver transplant center practice in response to COVID‐19: Unmasking dramatic center‐level variability

text: The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has been devastating to health care delivery in many parts of the US and has had a significant impact on organ transplantation. With shelter‐in‐place orders, outpatient clinics transitioned to telemedicine, and the threat of hospitals being overrun with COVID‐19 patients, liver transplant programs have been faced with the challenge of balancing patient and staff safety while operating in a resource limited environment.


Please cite this paper as: Martin et al. (2012) Multiple versus single virus respiratory infections: viral load and clinical disease severity in hospitalized children. Influenza and Other Respiratory Viruses 6(1), 71–77. Background Molecular testing for viral pathogens has resulted in increasing detection of multiple viruses in respiratory secretions of ill children. The clinical impact of multiple virus infections on clinical presentation and outcome is unclear. Objectives To compare clinical characteristics and viral load between children with multiple virus versus single virus illnesses. Patients/methods Eight hundred and ninety‐three residual nasal wash samples from children treated for respiratory illness at Children’s Hospital, Seattle, from September 2003 to September 2004 were evaluated by quantitative PCR for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), influenza (Flu), parainfluenza, adenoviruses, and coronaviruses (CoV). Illness severity and patient characteristics were abstracted from medical charts. Results Coinfections were identified in 103 (18%) of 566 virus‐positive samples. Adenovirus was most commonly detected in coinfections (52%), followed by CoV (50%). Illnesses with a single virus had increased risk of oxygen requirement (P = 0·02), extended hospital stays (P = 0·002), and admissions to the inpatient (P = 0·02) or intensive care units (P = 0·04). For Adv and PIV‐1, multiple virus illnesses had a significantly lower viral load (log(10) copies/ml) than single virus illnesses (4·2 versus 5·6, P = 0·007 and 4·2 versus 6·9, P < 0·001, respectively). RSV, Flu‐A, PIV‐3, and hMPV viral loads were consistently high whether or not another virus was detected. Conclusions Illnesses with multiple virus detections were correlated with less severe disease. The relationship between viral load and multiple virus infections was virus specific, and this may serve as a way to differentiate viruses in multiple virus infections.


title: Enhanced Design of PPE Based on Electrostatic Principle to Eliminate Viruses (SARS-CoV-2)

text: The ongoing global pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is in the crucial stage. The vaccine is still at the developing stage. Currently, the only way to check the spreading of this virus is self-isolation. It is reported that a good number of health workers are infected while treating patients suffering from COVID 19. Therefore, an effort is made to develop a system that can enhance safety and check unwanted viruses. Although the complete specification of the SARS-CoV-2 is yet to be evaluated, the present work considers the characteristic of SARS-CoV-1, which closely relates to that of SARS-CoV-2. The proteins are one of the most important structural and functional molecules of the virus; therefore, few properties of a protein are considered. In this work, we propose a sanitization procedure of the personal protective equipment (PPE), such as gloves and masks, before and after the use, by employing high voltage charge generator (30 kV) from a very low DC source of 5 V to eliminate the virus from the surface of PPE. The positive output is connected to a metallic surface coated with carbon nanotubes (CNT) or a metallic surface ablated using lithography to achieve desired nano-grooves of 200 nm. At the tip of these nano-grooves, a very high electric field is generated which readily ionises the air in the vicinity of the tip. The high electric field alters the induced dipole of the protein of the virus, causing permanent damage in terms of electroporation. Further positive salt ions diffuse into the protein of the viruses, causing it inactive and disintegrate.


title: Emerging infectious diseases and outbreaks: implications for women’s reproductive health and rights in resource-poor settings

text: This century is witnessing dramatic changes in the health needs of the world’s populations. The double burden of infectious and chronic diseases constitutes major causes of morbidity and mortality. Over the last two decades, there has been a rise in infectious diseases, including the severe acute respiratory syndrome virus (SARS), the H1N1 pandemic influenza, the Ebolavirus and the Covid-19 virus. These diseases have rapidly spread across the world and have reminded us of the unprecedented connectivity that defines our modern civilization. Though some countries have made substantial progress toward improving global surveillance for emerging infectious diseases (EIDs), the vast majority of Low-and Middle-income Countries (LMICs) with fragile health systems and various system-related bottlenecks remain vulnerable to outbreaks and, as such, experience dramatic social and economic consequences when they are reported. Lessons learned from past outbreaks suggest that gender inequalities are common across a range of health issues relating to Sexual and Reproductive Health and Rights (SRHR), with women being particularly disadvantaged, partially due to the burden placed on them. Though these countries are striving to improve their health systems and be more inclusive to this vulnerable group, the national/ global outbreaks have burdened the overall system and thus paralyzed normal services dedicated to the delivery of Sexual and Reproductive Health (SRH) services. In this paper, we discuss the global commitments to SRH, the impact of the EIDs on the LMICs, the failure in the delivery of SRH services, and the strategies for successful implementation of recovery plans that must address the specific and differentiated needs of women and girls in resource-poor settings.


Berufspolitik BvDU


title: Epidemiological analysis of the early 38 fatalities in Hubei, China, of the coronavirus disease 2019

text: BACKGROUND: Since the emergence of coronavirus disease 2019 (COVID-19) in Hubei province of China by the end of 2019, it has burned its way across the globe, resulting in a still fast-growing death toll that far exceeded those from severe acute respiratory syndrome (SARS) in less than two months. As there is a paucity of evidence on which population is more likely to progress into severe conditions among cases, we looked into the first cluster of death cases, aiming to add to current evidence and reduce panic among the population. METHODS: We prospectively collected the demographic and clinical data of the first 38 fatalities whose information was made public by the Health Commission of Hubei province and the official Weibo account of China Central Television news center, starting from 9 January through 24 January 2020. The death cases were described from four aspects (gender and age characteristics, underlying diseases, the time course of death, symptoms at the incipience of illness and hospital admission). RESULTS: Among the 38 fatalities, 71.05% were male, and 28.95% were female, with the median age of 70 years (interquartile range (IQR) = 65-81). Persons aged 66-75 made up the largest share. Twenty-five cases had a history of chronic diseases. The median time between the first symptoms and death was 12.50 days (IQR = 10.00-16.25), while the median time between the admission and death was 8.50 (IQR = 5.00-12.00) days. In persons aged over 56 years, the time between the first symptoms and death decreased with age, and so did the time between the admission and death, though the latter increased again in persons aged over 85 years. The major first symptoms included fever (52.63%), cough (31.58%), dyspnea (23.68%), myalgia and fatigue (15.79%). CONCLUSIONS: Among the death cases, persons with underlying diseases and aged over 65 made up the majority. The time between the first symptoms and death decreased with the advanced age. In all the age groups, males dominated the fatalities.


LETTER TO THE EDITOR: Labor and Delivery Guidance for COVID-19


title: A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8

text: Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA–RNA and RNA–protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results of minigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication.


SARS-CoV, MERS-CoV and now the 2019-novel CoV: Have we investigated enough about coronaviruses? – A bibliometric analysis


title: Proteasome inhibition reduces avian reovirus replication and apoptosis induction in cultured cells

text: Abstract The interplay between avian reovirus (ARV) replication and apoptosis and proteasome pathway was studied in cultured cells. It is shown that inhibition of the proteasome did not affect viral entry and host cell translation but had influence on ARV replication and ARV-induced apoptosis. Evidence is provided to demonstrate that ubiquitin-proteasome blocked ARV replication at an early step in viral life cycle. However, viral transcription and protein translation were also reduced markedly after addition of proteasome inhibitor MG132. Treatment of BHK-21 cells with the MG132 markedly decreased virus titer as well as prevented virus-induced apoptosis. The expression of ARV proteins σC, σA, and σNS was also reduced markedly, suggesting that suppression of virus replication is due to down-regulation of these ARV proteins by ubiquitin-proteasome system. MG132 was also shown to suppress ARV σC-induced phosphrylation of p53 on serine 46, caspase 3 activities, and DNA fragmentation leading to complete inhibition of ARV-induced apoptosis.


title: Animal-based national surveillance for zoonotic disease: Quality, limitations, and implications of a model system for monitoring rabies

text: Abstract Surveillance for zoonotic diseases among wildlife is a research and public health challenge. The inherent limitations posed by the requisite human–animal interactions are often undefined and underappreciated. The national surveillance system for animal rabies in the United States was examined as a model system; reporting of animal rabies is legally mandated, each case of rabies is laboratory confirmed, and data have been consistently collected for more than 50 years. Factors influencing the monthly counts of animal rabies tests reported during 1992–2001 were assessed by univariate and multivariable regression methods. The suitability of passively collected surveillance data for determining the presence or absence of the raccoon-associated variant of rabies within states and within individual counties was assessed by determining critical threshold values from the regression analyses. The size of the human population and total expenditures within a county accounted for 72% and 67%, respectively, of the variance in testing. The annual median number of rabies tests performed was seven for counties without rabies, 22 for counties with non-raccoon rabies, and 34 for counties with raccoon rabies. Active surveillance may be required in locales with sparse human populations when a high degree of confidence in the status of rabies is required.


title: eHealth in kidney care

text: eHealth is gaining momentum in nephrology, although evidence for its efficacy remains unclear and challenges to its widespread adoption persist. Successful integration of eHealth into kidney care will require patient engagement to develop effective interventions and issues such as data validity, regulation, oversight and adequate infrastructure to be addressed.


title: What face mask for what use in the context of COVID-19 pandemic? The French guidelines

text: Summary In the context of the COVID-19 pandemic, wearing a face mask has become usual and ubiquitous, in both hospitals and community. However, the general public is consuming surgical or filtering face piece (FFP) masks irrespective of their specificity, leading to global supply shortage for the most exposed persons, which are healthcare workers. This underlines the urgent need to clarify the indications of the different categories of mask, in order to rationalize their use. The study herein specifies the French position for the rational use of respiratory protective equipment for healthcare workers.


title: Identification of influenza A nucleoprotein as an antiviral target

text: Influenza A remains a significant public health challenge because of the emergence of antigenically shifted or highly virulent strains(1,2,3,4,5). Antiviral resistance to available drugs such as adamantanes or neuraminidase inhibitors has appeared rapidly(6,7,8,9), creating a need for new antiviral targets and new drugs for influenza virus infections. Using forward chemical genetics, we have identified influenza A nucleoprotein (NP) as a druggable target and found a small-molecule compound, nucleozin, that triggers the aggregation of NP and inhibits its nuclear accumulation. Nucleozin impeded influenza A virus replication in vitro with a nanomolar median effective concentration (EC(50)) and protected mice challenged with lethal doses of avian influenza A H5N1. Our results demonstrate that viral NP is a valid target for the development of small-molecule therapies. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nbt.1638) contains supplementary material, which is available to authorized users.


title: Well-controlled vs Poorly-controlled Diabetes in Patients with COVID-19: Are There Any Differences in Outcomes and Imaging Findings?

text: AIMS: Herein, we aimed to compare the clinical outcomes and imaging findings between COVID-19 patients with well-controlled diabetes and those with poorly-controlled diabetes. METHODS: In this retrospective single-center study, 117 patients with coexistent COVID-19 and type 2 diabetes mellitus were included. Patients were divided into two groups based on HbA1c values. The chest computed tomography (CT) score was defined by the summation of individual scores from 5 lung lobes: scores of 0, 1, 2, 3, 4 and 5 were respectively assigned for each lobe if pulmonary involvement was 0%, less than 5%, 5%-25%, 26%-49%, 50%-75%, or more than 75% of each region. Clinical data and laboratory parameters were also collected from patients’ medical records. RESULTS: Among all patients with diabetes, 93 (79.5%) patients had poor-controlled diabetes and 24 (20.5%) had well-controlled diabetes; 66 (56.4%) patients were male and the median age was 66 years (IQR, 55-75 years). The chest CT severity scores were not significantly different between patients with well-controlled diabetes and those with poorly-controlled diabetes (p=0.33). Also, the mortality and recovery rates were similar between the two groups (p=0.54 and p=0.85, respectively). CONCLUSION: Based on the results, clinical outcomes and chest CT severity scores are similar between patients with well-controlled and poorly-controlled diabetes among the Iranian population with COVID-19.


title: Identification of an enterovirus recombinant with a torovirus-like gene insertion during a diarrhea outbreak in fattening pigs

text: Diarrhea outbreaks in pig farms have raised major concerns in Europe and USA, as they can lead to dramatic pig losses. During a suspected outbreak in Belgium of porcine epidemic diarrhea virus (PEDV), we performed viral metagenomics to assess other potential viral pathogens. Although PEDV was detected, its low abundance indicated that other viruses were involved in the outbreak. Interestingly, a porcine bocavirus and several enteroviruses were most abundant in the sample. We also observed the presence of a porcine enterovirus genome with a gene insertion, resembling a C28 peptidase gene found in toroviruses, which was confirmed using re-sequencing, bioinformatics, and proteomics approaches. Moreover, the predicted cleavage sites for the insertion suggest that this gene was being expressed as a single protein, rather than a fused protein. Recombination in enteroviruses has been reported as a major mechanism to generate genetic diversity, but gene insertions across viral families are rather uncommon. Although such inter-family recombinations are rare, our finding suggests that these events may significantly contribute to viral evolution.


title: Purification and Electron Cryomicroscopy of Coronavirus Particles

text: Intact, enveloped coronavirus particles vary widely in size and contour, and are thus refractory to study by traditional structural means such as X-ray crystallography. Electron microscopy (EM) overcomes some problems associated with particle variability and has been an important tool for investigating coronavirus ultrastructure. However, EM sample preparation requires that the specimen be dried onto a carbon support film before imaging, collapsing internal particle structure in the case of coronaviruses. Moreover, conventional EM achieves image contrast by immersing the specimen briefly in heavy-metal-containing stain, which reveals some features while obscuring others. Electron cryomicroscopy (cryo-EM) instead employs a porous support film, to which the specimen is adsorbed and flash-frozen. Specimens preserved in vitreous ice over holes in the support film can then be imaged without additional staining. Cryo-EM, coupled with single-particle image analysis techniques, makes it possible to examine the size, structure and arrangement of coronavirus structural components in fully hydrated, native virions. Two virus purification procedures are described.


title: FilmArray® respiratory panel performance in respiratory samples from neonatal care units

text: Abstract FilmArray Respiratory Panel (RP) (Idaho Technology, Inc., Salt Lake City, UT, USA) performance was retrospectively evaluated in respiratory samples collected from neonates in 2 reference neonatology units. Using the FilmArray RP assay, 121/152 (79.6%) samples were positive for at least 1 respiratory virus, while 31/152 (20.4%) were negative. FilmArray RP results were concordant in 68/72 (94.4%) respiratory samples tested with laboratory-developed real-time PCR assays, while in 4/72 (5.6%) samples, the FilmArray RP assay detected an additional virus (2 human rhinovirus/enterovirus and 2 bocavirus). In addition, FilmArray RP results for 70 of 80 (87.5%) respiratory samples tested were concordant with the Seegene Seeplex RV15® detection assay (Seegene, Inc., Seoul, South Korea), while 10/80 (12.5%) were discordant. The advantages of the FilmArray RP are the rapid detection of respiratory viruses (1 hour), the wide number of pathogens detectable in a single assay, and the reduced hands-on time.


title: Analysis of the entry mechanism of Crimean-Congo hemorrhagic fever virus, using a vesicular stomatitis virus pseudotyping system

text: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease causing severe hemorrhagic symptoms with a nearly 30 % case-fatality rate in humans. The experimental use of CCHF virus (CCHFV), which causes CCHF, requires high-biosafety-level (BSL) containment. In contrast, pseudotyping of various viral glycoproteins (GPs) onto vesicular stomatitis virus (VSV) can be used in facilities with lower BSL containment, and this has facilitated studies on the viral entry mechanism and the measurement of neutralizing activity, especially for highly pathogenic viruses. In the present study, we generated high titers of pseudotyped VSV bearing the CCHFV envelope GP and analyzed the mechanisms involved in CCHFV infection. A partial deletion of the CCHFV GP cytoplasmic domain increased the titer of the pseudotyped VSV, the entry mechanism of which was dependent on the CCHFV envelope GP. Using the pseudotype virus, DC-SIGN (a calcium-dependent [C-type] lectin cell-surface molecule) was revealed to enhance viral infection and act as an entry factor for CCHFV.


title: Human coronavirus NL-63 infection in a Brazilian patient suspected of H1N1 2009 influenza infection: Description of a fatal case

text: Abstract Human coronaviruses (HCoVs) cause upper respiratory tract and occasionally lower respiratory tract diseases. The recently described human coronavirus NL63 has not been well investigated among Brazilian patients. We reported the clinical course of an HCoV-NL63 infection in a hospitalised patient suspected of H1N1 2009 infection during the second pandemic wave of influenza activity. A 46-year-old female, health care worker with diabetes and presenting with influenza-like illness (ILI) was admitted to the hospital. During 9 days of influenza-like symptoms, the patient had diabetes decompensation, haemorrhagic pneumonia, rhabdomyolysis, respiratory and renal failure, pericarditis, and brain edema and died. HCoV-NL63 may be a causative agent of previously unexplained respiratory illnesses.


title: Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21st century: a prospective study on the Mediterranean coast of Spain

text: This study presents data from a prospective study of adult patients with community-acquired pneumonia (CAP). Of 493 patients included in the study, 223 (45.2%) were aged ≥ 65 years, and 265 (53.7%) had one or more underlying diseases, mostly chronic obstructive pulmonary disease, diabetes mellitus or dementia. In total, 281 microorganisms were identified in 250 (50.7%) patients, with two or more pathogens detected in 28 (5.7%) cases. Microbial diagnosis varied according to age, severity, co-morbidity and site-of-care, but there was much overlap among groups. Streptococcus pneumoniae was the single most prevalent organism in outpatients, patients admitted to hospital, and patients who died, either as a single pathogen or combined with another organism. Infections caused by ‘atypical’ pathogens were seen across all groups, including the elderly and patients with co-morbidities. Mortality varied according to the pneumonia severity index (PSI) of the pneumonia patient outcomes research team. Shock (OR 34.48), an age of > 65 years (OR 25) and altered mental status (OR 9.92) were factors associated independently with 30-day mortality. Key findings from this study were the advanced age of the population with CAP, and the high prevalence of dementia as an underlying disease. The study also revealed that microbiological diagnosis of CAP remains problematic. Although certain epidemiological features may help to predict the microbial aetiology, the overlap among groups reduces the usefulness of this information in guiding therapeutic decisions. Greater effort should be made to improve identification methods for microbial pathogens causing CAP.


Ebola: between mathematics and reality


title: Combining Procalcitonin and Rapid Multiplex Respiratory Virus Testing for Antibiotic Stewardship in Older Adult Patients With Severe Acute Respiratory Infection

text: Abstract Objectives Virus infection is underevaluated in older adults with severe acute respiratory infections (SARIs). We aimed to evaluate the clinical impact of combining point-of-care molecular viral test and serum procalcitonin (PCT) level for antibiotic stewardship in the emergency department (ED). Design A prospective twin-center cohort study was conducted between January 2017 and March 2018. Setting and Participants Older adult patients who presented to the ED with SARIs received a rapid molecular test for 17 respiratory viruses and a PCT test. Measures To evaluate the clinical impact, we compared the outcomes of SARI patients between the experimental cohort and a propensity score–matched historical cohort. The primary outcome was the proportion of antibiotics discontinuation or de-escalation in the ED. The secondary outcomes included duration of intravenous antibiotics, length of hospital stay, and mortality. Results A total of 676 patients were included, of which 169 patients were in the experimental group and 507 patients were in the control group. More than one-fourth (27.9%) of the patients in the experimental group tested positive for virus. Compared with controls, the experimental group had a significantly higher proportion of antibiotics discontinuation or de-escalation in the ED (26.0% vs 16.1%, P = .007), neuraminidase inhibitor uses (8.9% vs 0.6%, P < .001), and shorter duration of intravenous antibiotics (10.0 vs 14.5 days, P < .001). Conclusions and Implications Combining rapid viral surveillance and PCT test is a useful strategy for early detection of potential viral epidemics and antibiotic stewardship. Clustered viral respiratory infections in a nursing home is common. Patients transferred from nursing homes to ED may benefit from this approach.


How to safeguard children’s mental health during emergencies


title: IL-12 and Viral Infections

text: Abstract Interleukin-12 activates natural killer cells and promotes the differentiation of Th1 CD4+ cells; it is a critical factor in viral immunity. IL-12 is secreted by antigen presenting cells including dendritic cells, macrophages and astrocytes, both in tissues and in secondary lymphoid organs. Experimental studies have shown that administration of the cytokine rapidly activates both innate and specific immune responses; this results in enhanced host cellular responses and generally, promotes clearance of virus and host recovery from infection. The observations of many laboratories, studying viral immunity to both RNA and DNA based pathogens, are summarized.


title: Detection of enteroviruses and parechoviruses by a multiplex real-time RT-PCR assay

text: Abstract Detection of all enteroviruses while excluding cross-detection of rhinoviruses is challenging because of sequence similarities in the commonly used conserved targets for molecular assays. In addition, simultaneous detection and differentiation of enteroviruses and parechoviruses would be beneficial because of a similar clinical picture presented by these viruses. A sensitive and specific real-time RT-PCR protocol that can address these clinical needs would be valuable to molecular diagnostic laboratories. Here we report a multiplex nucleic acid based assay using hydrolysis probes targeting the 5′ non-translated region for the detection and differentiation of enteroviruses and parechoviruses without cross-detection of rhinoviruses. This assay has been shown to detect enteroviruses belonging to the different species in a variety of specimen types without detecting the different species of rhinoviruses. Laboratory validation shows the assay to be sensitive, specific, reproducible, easy to set up and uses generic cycling conditions. This assay can be implemented for diagnostic testing of patient samples in a high throughput fashion.


title: World Health Assembly Agendas and trends of international health issues for the last 43 years: Analysis of World Health Assembly Agendas between 1970 and 2012

text: Abstract Objective To analyse the trends and characteristics of international health issues through agenda items of the World Health Assembly (WHA) from 1970 to 2012. Methods Agendas in Committees A/B of the WHA were classified as Administrative or Technical and Health Matters. Agenda items of Health Matters were sorted into five categories by the WHO reform in the 65th WHA. The agenda items in each category and sub-category were counted. Results There were 1647 agenda items including 423 Health Matters, which were sorted into five categories: communicable diseases (107, 25.3%), health systems (81, 19.1%), noncommunicable diseases (59, 13.9%), preparedness surveillance and response (58, 13.7%), and health through the life course (36, 8.5%). Among the sub-categories, HIV/AIDS, noncommunicable diseases in general, health for all, millennium development goals, influenza, and international health regulations, were discussed frequently and appeared associated with the public health milestones, but maternal and child health were discussed three times. The number of the agenda items differed for each Director-General's term of office. Conclusions The WHA agendas cover a variety of items, but not always reflect international health issues in terms of disease burden. The Member States of WHO should take their responsive roles in proposing more balanced agenda items.


title: Current applications and future trends of molecular diagnostics in clinical bacteriology

text: Molecular diagnostics of infectious diseases, in particular, nucleic-acid-based methods, are the fastest growing field in clinical laboratory diagnostics. These applications are stepwise replacing or complementing culture-based, biochemical, and immunological assays in microbiology laboratories. The first-generation nucleic acid assays were monoparametric such as conventional tests, determining only a single parameter. Improvements and new approaches in technology now open the possibility for the development of multiparameter assays using microarrays, multiplex nucleic acid amplification techniques, or mass spectrometry, while the introduction of closed-tube systems has resulted in rapid microbial diagnostics with a subsequently reduced contamination risk. Whereas the first assays were focused on the detection and identification of microbial pathogens, these new technologies paved the way for the parallel determination of multiple antibiotic resistance determinants or to perform microbial epidemiology and surveillance on a genetic level.


title: Implications of altered replication fidelity on the evolution and pathogenesis of coronaviruses

text: RNA virus evolution results from viral replication fidelity and mutational robustness in combination with selection. Recent studies have confirmed the impact of increased fidelity on RNA virus replication and pathogenesis; however, the impact of decreased fidelity is less defined. Coronaviruses have the largest RNA genomes, and encode an exoribonuclease activity that is required for high-fidelity replication. Genetically stable exoribonuclease mutants will allow direct testing of viral mutational tolerance to RNA mutagens and other selective pressures. Recent studies support the hypothesis that coronavirus replication fidelity may result from a multi-protein complex, suggesting multiple pathways to disrupt or alter virus fidelity and diversity, and attenuate pathogenesis.


title: COVID‐19 under spotlight: A close look at the origin, transmission, diagnosis, and treatment of the 2019‐nCoV disease

text: Months after the outbreak of a new flu‐like disease in China, the entire world is now in a state of caution. The subsequent less‐anticipated propagation of the novel coronavirus disease, formally known as COVID‐19, not only made it to headlines by an overwhelmingly high transmission rate and fatality reports, but also raised an alarm for the medical community all around the globe. Since the causative agent, SARS‐CoV‐2, is a recently discovered species, there is no specific medicine for downright treatment of the infection. This has led to an unprecedented societal fear of the newly born disease, adding a psychological aspect to the physical manifestation of the virus. Herein, the COVID‐19 structure, epidemiology, pathogenesis, etiology, diagnosis, and therapy have been reviewed.


Self‐reported olfactory loss in COVID‐19: is it really a favorable prognostic factor?


title: All India Ophthalmological Society – Indian Journal of Ophthalmology consensus statement on preferred practices during the COVID-19 pandemic

text: The COVID-19 pandemic has taken tragic proportions and has disrupted lives globally. In the wake of governmental lockdowns, ophthalmologists need practical and actionable guidelines based on advisories from national health departments on how to conduct their duties during nationwide lockdowns and after these are lifted. In this paper, we present a preferred practice pattern (PPP) based on consensus discussions between leading ophthalmologists and health care professionals in India including representatives from major governmental and private institutions as well as the All India Ophthalmological Society leadership. In this document, the expert panel clearly defines the range of activities for Indian ophthalmologists during the ongoing lockdown phase and precautions to be taken once the lockdown is lifted. Guidelines for triage, governmental guidelines for use of personal protective equipment from ophthalmologists' point of view, precautions to be taken in the OPD and operating room as well as care of various ophthalmic equipment have been described in detail. These guidelines will be applicable to all practice settings including tertiary institutions, corporate and group practices and individual eye clinics and should help Indian ophthalmologists in performing their professional responsibilities without being foci of disease transmission.


title: Steroid responsiveness and wheezing phenotypes

text: Summary Oral corticosteroids are the cornerstone of management of acute moderate or severe asthma whilst preventive inhaled corticosteroids are the mainstay of the preventive management of children with asthma. Yet, variation in the magnitude of response to corticosteroids has been observed. There is increasing evidence that preschool-aged children with viral-induced asthma may display a certain degree of corticosteroid resistance, requiring higher doses of corticosteroids to overcome it. The identification of determinants of responsiveness is complicated by design issues, including heterogeneous populations of children with asthma and bronchiolitis or of children with viral-induced and multi-trigger asthma phenotypes in published trials. Potential key determinants of responsiveness may include age, trigger, phenotype, tobacco smoke exposure and genotype. The mechanistic pathway for corticoresistance may originate from a gene-environment interaction, leading to non-eosinophilic airway inflammation. The clinician should carefully confirm the diagnosis of asthma and ascertain the phenotype to select appropriate phenotype-specific therapy.


title: Tanreqing Injection Attenuates Lipopolysaccharide-Induced Airway Inflammation through MAPK/NF-κB Signaling Pathways in Rats Model

text: Background. Tanreqing injection (TRQ) is a commonly used herbal patent medicine for treating inflammatory airway diseases in view of its outstanding anti-inflammatory properties. In this study, we explored the signaling pathways involved in contributions of TRQ to LPS-induced airway inflammation in rats. Methods/Design. Adult male Sprague Dawley (SD) rats randomly divided into different groups received intratracheal instillation of LPS and/or intraperitoneal injection of TRQ. Bronchoalveolar Lavage Fluid (BALF) and lung samples were collected at 24 h, 48 h, and 96 h after TRQ administration. Protein and mRNA levels of tumor necrosis factor- (TNF-) α, Interleukin- (IL-) 1β, IL-6, and IL-8 in BALF and lung homogenate were observed by ELISA and real-time PCR, respectively. Lung sections were stained for p38 MAPK and NF-κB detection by immunohistochemistry. Phospho-p38 MAPK, phosphor-extracellular signal-regulated kinases ERK1/2, phospho-SAPK/JNK, phospho-NF-κB p65, phospho-IKKα/β, and phospho-IκB-α were measured by western blot analysis. Results. The results showed that TRQ significantly counteracted LPS-stimulated release of TNF-α, IL-1β, IL-6, and IL-8, attenuated cells influx in BALF, mitigated mucus hypersecretion, suppressed phosphorylation of NF-κB p65, IκB-α, ΙKKα/β, ERK1/2, JNK, and p38 MAPK, and inhibited p38 MAPK and NF-κB p65 expression in rat lungs. Conclusions. Results of the current research indicate that TRQ possesses potent exhibitory effects in LPS-induced airway inflammation by, at least partially, suppressing the MAPKs and NF-κB signaling pathways, in a general dose-dependent manner.


title: Cultural shift towards sustainability in the construction industry of Hong Kong

text: Abstract Sustainable development is forward-looking; it is a continuous mission for future developments of human society. A genuinely sustainable society is one that initiates developments in sustainable ways. The development of a genuinely sustainable society is supported by its citizens who think and act according to a recognized code of conduct - the sustainable culture. Similar to other forms of culture, sustainable culture of a society is not static, but changes over time. The changes found in a sustainable culture are reflections of the status of sustainability in a society and these changes should be measured from time to time. The resulting measurement gives very important information for decision-makers, in the government and in the private sector, to examine the magnitude of changes that have taken place in a given period of time. The results will also enable them to review and adjust policies in order to better accommodate changes according to the trends of society. This paper provides a method – the T-model, to investigate and measure the extent of change of sustainable culture through two extensive surveys among participants of the construction industry of Hong Kong. The change in sustainable culture is reflected by the change in attitude and practice among construction participants, this can be found in their performance in project development, design and construction operations. The data of these changes are collected and converted to numerical scores. The T-model synthesized these scores and revealed the change of sustainable culture within the specific study time frame.


title: Enteric adenoviruses

text: In 1978, the World Health Organisation initiated a programme for global prevention and control of childhood diarrhoeas. As a result, the relative importance of various pathogens in the aetiology of diarrhoea in many parts of the world has been recognised. Rotavirus, which ranks as the most prevalent viral pathogen in childhood diarrhoea may be closer to control as many vaccines are in sight. This has been made possible due to a decade of intense research since its discovery. E Ad, which probably ranks as the second most important viral pathogen has not received much attention. As has been discussed, much information has to be gathered about this virus, before W.H.O's. goal of controlling childhood diarrhoea is realised.


title: Adjustments in the Use of Intravesical Instillations of Bacillus Calmette-Guérin for High-risk Non–muscle-invasive Bladder Cancer During the COVID-19 Pandemic

text: Non–muscle-invasive bladder cancer patients with COVID-19 are more likely to develop acute respiratory distress syndrome. Thus, several adjustments to the use of intravesical instillations of bacillus Calmette-Guérin should be made during the current pandemic to limit the risk of contamination.


Pädiatrie aktuell – Forschung kurz notiert


title: Development of a one-step RT-PCR assay for detection of pancoronaviruses (α-, β-, γ-, and δ-coronaviruses) using newly designed degenerate primers for porcine and avian `fecal samples

text: Abstract Coronaviruses (CoVs) are critical human and animal pathogens because of their potential to cause severe epidemics of respiratory or enteric diseases. In pigs, the newly emerged porcine deltacoronavirus (PDCoV) and re-emerged porcine epidemic diarrhea virus (PEDV) reported in the US and Asia, as well as the discovery of novel CoVs in wild bats or birds, has necessitated development of improved detection and control measures for these CoVs. Because the previous pancoronavirus (panCoV) RT-PCR established in our laboratory in 2007–2011 did not detect deltacoronaviruses (δ-CoVs) in swine fecal and serum samples, our goal was to develop a new panCoV RT-PCR assay to detect known human and animal CoVs, including δ-CoVs. In this study, we designed a new primer set to amplify a 668 bp-region within the RNA-dependent RNA polymerase (RdRP) gene that encodes the most conserved protein domain of α-, β-, γ-, and δ-CoVs. We established a one-step panCoV RT-PCR assay and standardized the assay conditions. The newly established panCoV RT-PCR assay was demonstrated to have a high sensitivity and specificity. Using a panel of 60 swine biological samples (feces, intestinal contents, and sera) characterized by PEDV, PDCoV and transmissible gastroenteritis virus-specific RT-PCR assays, we demonstrated that sensitivity and specificity of the newly established panCoV RT-PCR assay were 100%. 400 avian fecal (RNA) samples were further tested simultaneously for CoV by the new panCoV RT-PCR and a one-step RT-PCR assay with the δ-CoV nucleocapsid-specific universal primers. Four of 400 avian samples were positive for CoV, three of which were positive for δ-CoV by the conventional RT-PCR. PanCoV RT-PCR fragments for 3 of the 4 CoVs were sequenced. Phylogenetic analysis revealed the presence of one γ-CoV and two δ-CoV in the sequenced samples. The newly designed panCoV RT-PCR assay should be useful for the detection of currently known CoVs in animal biological samples.


title: The clinical impact of pneumocystis and viral PCR testing on bronchoalveolar lavage in immunosuppressed patients

text: Abstract Introduction Pulmonary infiltrates in immunosuppressed patients are common. Yields from bronchoscopy with bronchoalveolar lavage (BAL) has been reported to be between 31 and 65%. The clinical impact of pneumocystis and viral Polymerase chain reaction (PCR) testing on BAL has not been extensively evaluated in a mixed immunosuppressed patient population. Methods We performed a retrospective chart review of immunosuppressed adults with pulmonary infiltrates who underwent BAL at the University of Rochester Medical Center. Only one BAL per patient was included. We compared the rate of positive PCR testing to conventional testing. We then investigated factors associated with positive PCR testing. Finally, we assessed for changes in antimicrobial therapy after bronchoscopy. Results Three hundred and fifty-nine patients underwent BAL with 249 patients having pneumocystis PCR testing and 142 having viral PCR testing. Pneumocystis identification occurred in 43 patients and viral species identification occurred in 56 patients. PCR testing increased pneumocystis identification compared to microscopy, 14% vs. 5%, p = 0.01, and viral identification compared to culture, 25% vs. 6%, p = 0.0001. Of the patients with positive pneumocystis PCR testing 49% had antibiotics stopped, 66% were started on anti-pneumocystis therapy, and only 6% did not receive treatment. There was no difference in the number of patients with antibiotics stopped based on viral PCR testing results. Discussion PCR testing increases BAL yield in immunosuppressed patients compared to conventional testing. Pneumocystis identified by PCR only may cause a self-limited infection and may not require antimicrobial therapy. PCR testing should be included in the evaluation of pulmonary infiltrates in immunosuppressed patients.


title: Crisis management and recovery: how restaurants in Hong Kong responded to SARS

text: Abstract The 2003 Severe Acute Respiratory Syndrome (SARS) outbreak constitutes an example of the many crises that a restaurant may encounter. This article reviews a typology of crises, examines the crisis response of restaurants in Hong Kong, illustrates how local restaurants deal with this unprecedented situation and develop strategies for management and recovery. The lessons and experience gained from dealing with the SARS crisis serve as references for restaurants in other destinations when they face similar crises in future.


title: Chapter 9 Recovery from Infection

text: This chapter addresses the factors involved in recovery from infection. Antibody and cellular responses (CMI) are considered. The mechanisms by which antibodies neutralise viruses/prevent infection are described, as is the involvement of antibody in bacterial and protozoal diseases. The role of CMI in recovery from specific bacterial, protozoal and viral infections is considered. The mechanisms of cell killing by cytotoxic T-cells is described and the role of NK cells and macrophages in pathogen clearance is discussed, as is the role of inflammation. Mechanisms by which the complement system acts and its role in vivo is discussed, as is the interferon response. Recovery from S. typhimurium is used to illustrate the multimechanistic nature of recovery. The role of temperature in recovery and pathogen factors that induce fever are considered. Tissue repair mechanisms are discussed, as is finally resistance to infection.


Response letter: handling of COVID-19 positive patients during the pandemic


Viral respiratory infections in BMT - A common cold is not just a cold in transplant recipients


title: Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review

text: For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.


2020 - The Year that Needed the Nurse: Considerations for Critical Care Nursing Research and Practice Emerging in the Midst of COVID-19


title: Propagation analysis and prediction of the COVID-19

text: Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.


title: Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola Virus in Rhesus Monkeys

text: The most recent Ebola virus outbreak in West Africa – unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected – highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae(1). No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we describe the discovery of a novel anti-EBOV small molecule antiviral, GS-5734, a monophosphoramidate prodrug of an adenosine analog. GS-5734 exhibits antiviral activity against multiple variants of EBOV in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternate substrate and RNA-chain terminator in primer-extension assays utilizing a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life = 14 h) and distribution to sanctuary sites for viral replication including testes, eye, and brain. In a rhesus monkey model of EVD, once daily intravenous administration of 10 mg/kg GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two of six treated animals. These results provide the first substantive, post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses – including filoviruses, arenaviruses, and coronaviruses – suggests the potential for expanded indications. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing.


WHO's Director-General candidates: visions and priorities


title: Phospholipid vesicles containing bovine heart mitochondrial cytochrome c oxidase exhibit proton translocating activity in the presence of gramicidin

text: Abstract Phospholipid vesicles containing bovine heart mitochondrial cytochrome c oxidase (COV) were characterized for electron transfer and proton translocating activities in the presence of the mobile potassium ionophore, valinomycin, and the channel-forming ionophore, gramicidin, in order to determine if the ionophores modify the functional properties of the enzyme. In agreement with previous work, incubation of COV with valinomycin resulted in a perturbation of the absorbance spectrum of oxidized heme aa 3 in the Soret region (430 nm); gramicidin had no effect on the heme aa 3 absorbance spectrum. Different concentrations of the two ionophores were required for maximum respiratory control ratios in COV; 40- to 70-fold higher concentrations of valinomycin were required to completely uncouple electron transfer activity when compared to gramidicin. The proton translocating activity of COV incubated with each ionophore gave a similar apparent proton translocated to electron transferred stoichiometry ( H+ e− ratio) of 0.66 ± 0.10. However, COV treated with low concentrations of gramicidin (0.14 mg/g phospholipid) exhibited 1.5- to 2.5-fold higher rates of alkalinization of the extravesicular media after the initial proton translocation reaction than did COV treated with valinomycin, suggesting that gramicidin allows more rapid equilibration of protons across the phospholipid bilayer during the proton translocation assay. Moreover, at higher concentrations of gramicidin (1.4 mg/g phospholipid), the observed H+ e− ratio decreased to 0.280 ± 0.020, while the rate of alkalinization increased an additional 2-fold, suggesting that at higher concentrations, gramicidin acts as a proton ionophore. These results support the hypothesis that cytochrome c oxidase is a redox-linked proton pump that operates at similar efficiencies in the presence of either ionophore. Low concentrations of gramicidin dissipate the membrane potential in COV most likely by a channel mechanism that is different from the carrier mechanism of valinomycin, yet does not make the phospholipid bilayer freely permeable to protons.