title: A multiepitopic theoretical fusion construct based on in-silico epitope screening of known vaccine candidates for protection against wide range of enterobacterial pathogens

text: Enterobacterial pathogens that have acquired antibiotic resistance genes are a leading cause of community and hospital acquired infections. In such a situation vaccination is considered as a better option to prevent such infections. In the current study reverse vaccinology approach has been used to select peptides from already known immunogenic proteins to design a chimeric construct. We selected Yersiniabactin receptor of Escherichia coli UMN026 and Flagellin of Stenotrophomonas maltophila. B-cell linear epitopes were predicted using Bepipred prediction tool. Peptide binding with reference sets of 27 alleles of MHC class I and class II was also analyzed. The predicted peptides-MHC complexes were further validated using simulation dynamics. The in-silico construction of chimera was done by restriction mapping and codon optimization. Chimera was evaluated using the immunoinformatic approach as done for the selected proteins. From the 673 amino acids of FyuA protein, a region from 1 to 492 was selected for containing more linear epitopes and the processing scores obtained were significant for MHC class I and class II binding. Similarly, from Flagellin, a region between 60 and 328 amino acids was selected and the peptides present in the selected region showed lower percentile ranks for binding with MHC molecules. The simulation studies validated the predictions of peptide-MHC complexes. The selected gene fragments accommodating maximum part of these peptides were used to design a chimaeric construct of 2454 bp. From the immunoinformatic analysis, the chimera was found to be more immunogenic in terms of increased number of B-cell and T-cell epitopes along with increased coverage of global populations with allelic variability.


title: DNA hybridization sensor based on aurothiomalate electroactive label on glassy carbon electrodes

text: In this work, a gold complex is used as electroactive label for monitoring hybridization assays on glassy carbon electrodes. Ionic gold is bound to a 30-mer sequence of the SARS (severe acute respiratory syndrome) virus, responsible for the atypical pneumonia, using sodium aurothiomalate. In order to label this single strand, a mixture of sodium aurothiomalate and the strand is prepared. Then, it is incubated for 24 h at 37 °C and, finally, free gold is separated from the labeled strand by a dialysis against a 0.15 M NaCl solution (pH 7.5). The DNA hybridization sensor is designed immobilizing the complementary probe on the pre-treated electrode surface and, then, the hybridization reaction takes place with the gold labeled strand. The electrochemical determination is based on the catalytic effect of electrodeposited gold on the reduction of silver ions. In non-stringent experimental conditions, a limit of detection of 15 fmol (30 μL) is obtained, and discrimination between a complementary oligonucleotide and a three-based mismatch complementary oligonucleotide is achieved. For the discrimination of a single-base mismatch, is needed to use stringent conditions (50% of formamide in the hybridization buffer).


title: Leader-mRNA Junction Sequences Are Unique for Each Subgenomic mRNA Species in the Bovine Coronavirus and Remain So Throughout Persistent Infection

text: Abstract The common leader sequence on bovine coronavirus subgenomic mRNAs and genome was determined. To examine leader-mRNA junction sequences on subgenomic mRNAs, specific oligodeoxynucleotide sets were used in a polymerase chain reaction to amplify junction sequences from either the positive-strand mRNA (eight of nine total identified species) or the negative-strand anti-mRNA (six of the nine species), and sequenced. The mRNA species studied were those for the N, M, S, and HE structural proteins and the 9.5-, 12.7-, 4.8-, and 4.9-kDa putative nonstructural proteins. By defining the leader-mRNA junction sequence as the sequence between (i) the point of mismatch between the leader and genome and (ii) the 3′ end of the consensus heptameric intergenic sequence [(U/A)C(U/C)AAAC)], or its variant, a unique junction sequence was found for each subgenomic mRNA species studied. In one instance (mRNA for the 12.7-kDa protein) the predicted intergenic sequence UCCAAAC was not part of the junction region, and in its place was the nonconforming sequence GGTAGAC that occurs just 15 nt downstream in the genome. Leader-mRNA junction sequences found after 296 days of persistent infection were the same as those found during acute infection (<18 hr postinfection). These data indicate that, in contrast to the closely related mouse hepatitis virus, the bovine coronavirus maintains a stable leader-mRNA junction sequence for each mRNA. Interestingly, this stability may be related to the fact that a UCUAA sequence element, postulated by others to be a regulator of the leader-mRNA fusion event, occurs only once within the 3′ flanking sequence of the genomic leader donor and once at intergenic sites in the bovine coronavirus genome, whereas it occurs two to four times at these sites in the mouse hepatitis coronavirus.


Pediatric Infectious Disease


title: Design, antiviral and cytostatic properties of isoxazolidine-containing amonafide analogues

text: Abstract A novel series of 5-arylcarbamoyl- and 5-arylmethyl-2-methylisoxazolidin-3-yl-3-phosphonates have been synthesized via cycloaddition of N-methyl-C-(diethoxyphosphoryl)nitrone with N-substituted naphthalimide acrylamides and N-allylnaphthalimides. All cis- and trans-isoxazolidine phosphonates obtained herein were assessed for antiviral activity against a broad range of DNA and RNA viruses. Isoxazolidines trans-9d and trans-9f exhibited the highest activity (EC50 =8.9μM) toward cytomegalovirus. Compounds cis- and trans-9d as well as cis- and trans-9f were found potent against HSV and Vaccinia viruses (EC50 in the 45–58μM range), whereas isoxazolidines 10a and 10d suppressed replication of Coxsackie B4 and Punta Toro viruses (EC50 in the 45–73μM range). Antiproliferative evaluation of all obtained isoxazolidines revealed the promising activity of cis-9b, cis-9d, trans-9d, cis-9e, trans-9e, cis-9f and trans-9f toward tested cancer cell lines with IC50 in the 1.1–19μM range.


title: Structural basis for RNA replication by the SARS-CoV-2 polymerase

text: Summary Nucleotide analog inhibitors, including broad-spectrum remdesivir and favipiravir, have shown promise in in vitro assays and some clinical studies for COVID-19 treatment, this despite an incomplete mechanistic understanding of the viral RNA-dependent RNA polymerase nsp12 drug interactions. Here we examine the molecular basis of SARS-CoV-2 RNA replication by determining the cryo-EM structures of the stalled pre-/post- translocated polymerase complexes. The structures show notable structural rearrangements occurring to nsp12 and its cofactors nsp7/nsp8 to accommodate the nucleic acid compared to the apo complex, while there are highly conserved residues in nsp12 positioning the template and primer for an in-line attack on the incoming nucleotide. Furthermore, we investigate the inhibition mechanisms of the triphosphate metabolite of remdesivir through structural and kinetic analyses. A transition model from the nsp7-nsp8 hexadecameric primase complex to the nsp12-nsp7-nsp8 polymerase complex is also proposed to provide clues for the understanding of the coronavirus transcription/replication machinery.


title: The Impact of the Covid‐19 Pandemic on Current Anatomy Education and Future Careers: A Student’s Perspective

text: As both an anatomy student and anatomy demonstrator, Anatomical Sciences Education has become my go-to journal to further my knowledge of the latest developments in anatomy education, innovations in pedagogical practice, and indeed perspectives on current affairs in the field.


docid: siinghks

title: Endocrine Surgery during the COVID-19 Pandemic: Recommendations from the Turkish Association of Endocrine Surgery

text: The 2019 novel coronavirus disease (COVID-19) was initially seen in Wuhan, China, in December 2019. World Health Organization classified COVID-19 as a pandemic after its rapid spread worldwide in a few months. With the pandemic, all elective surgeries and non-emergency procedures have been postponed in our country, as in others. Most of the endocrine operations can be postponed for a certain period. However, it must be kept in mind that these patients also need surgical treatment, and the delay time should not cause a negative effect on the surgical outcome or disease process. It has recently been suggested that elective surgical interventions can be described as medically necessary, time-sensitive (MeNTS) procedures. Some guidelines have been published on proper and safe surgery for both the healthcare providers and the patients after the immediate onset of the COVID-19 pandemic. We should know that these guidelines and recommendations are not meant to constitute a position statement, the standard of care, or evidence-based/best practice. However, these are mostly the opinions of a selected group of surgeons. Generally, only life-threatening emergency operations should be performed in the stage where the epidemic exceeds the capacity of the hospitals (first stage), cancer and transplantation surgery should be initiated when the outbreak begins to be controlled (second stage), and surgery for elective cases should be performed in a controlled manner with suppression of the outbreak (third stage). In this rapidly developing pandemic period, the plans and recommendations to be made on this subject are based on expert opinions by considering factors, such as the course and biology of the disease, rather than being evidence-based. In the recent reports of many endocrine surgery associations and in various reviews, it has been stated that most of the cases can be postponed to the third stage of the epidemic. We aimed to evaluate the risk reduction strategies and recommendations that can help plan the surgery, prepare for surgery, protect both patients and healthcare workers during the operation and care for the patients in the postoperative period in endocrine surgery.


title: Worldwide prevalence of viral infection in AECOPD patients: A meta-analysis

text: Abstract Background and objective Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease. On the other hand, viral infections of the airway are associated with the acute exacerbations of COPD. A systematic review and meta-analysis were performed to determine the prevalence rate of viral infections in acute exacerbations of COPD patients. Methods PubMed database was systematically searched for population-based prevalence studies (1930–2017). Fixed and random effects models were used for estimation of summary effect-sizes. Between-study heterogeneity and publication bias were also calculated. “Viral infections” and “COPD patients with exacerbations” were the two critical inclusion criteria. Results Twenty-eight studies were selected out of 26078 articles for the present review. The overall estimation of the prevalence of viral infection was 0.374 (95% C.I: 0.359–0.388). Also, the evident heterogeneity of viral infection was observed among the studies (Cochran Q test, p value < 0.001 and I-squared = 97.5%). The highest and lowest prevalence rate was related to rhinovirus and echovirus, respectively. Also, the results of this study showed that the prevalence of viral infection in exacerbated COPD patients has fluctuation during the years with a slight increase and decrease. Conclusions The results of this systematic review demonstrated that respiratory viral infections have an important role in the acute exacerbation of COPD (AECOPD). In addition, determining the exact geographic epidemiology of these viruses is very important to manage the treatment of these infections.


title: Faecal virome of red foxes from peri-urban areas

text: Abstract Red foxes (Vulpes vulpes) are the most abundant carnivore species in the Northern Hemisphere. Since their populations are well established in peri-urban and urban areas, they represent a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. In this study, we evaluated the faecal virome of juvenile and adult foxes from peri-urban areas in central Croatia. The dominating mammalian viruses were fox picobirnavirus and parvovirus. The highest number of viral reads (N =1412) was attributed to a new fox circovirus and complete viral genome was de novo assembled from the high-throughput sequencing data. Fox circovirus is highly similar to dog circoviruses identified in diseased dogs in USA and Italy, and to a recently discovered circovirus of foxes with neurologic disease from the United Kingdom. Our fox picobirnavirus was more closely related to the porcine and human picobirnaviruses than to known fox picobirnaviruses.


title: Combining network analysis with epidemiological data to inform risk-based surveillance: Application to hepatitis E virus (HEV) in pigs

text: Abstract Animal movements between farms are a major route of pathogen spread in the pig production sector. This study aimed to pair network analysis and epidemiological data in order to evaluate the impact of animal movements on pathogen prevalence in farms and assess the risk of local areas being exposed to diseases due to incoming movements. Our methodology was applied to hepatitis E virus (HEV), an emerging foodborne zoonotic agent of concern that is highly prevalent in pig farms. Firstly, the pig movement network in France (data recorded in 2013) and the results of a nation-wide seroprevalence study (data collected in 178 farms in 2009) were modelled and analysed. The link between network centrality measures of farms and HEV seroprevalence levels was explored using a generalised linear model. The in-degree and ingoing closeness of farms were found to be statistically associated with high HEV within-farm seroprevalence (p<0.05). Secondly, the risk of a French département (i.e. French local administrative areas) being exposed to HEV was calculated by combining the distribution of farm-level HEV prevalence in source départements with the number of movements coming from those same départements. By doing so, the risk of exposure for départements was mapped, highlighting differences between geographical patterns of HEV prevalence and the risk of exposure to HEV. These results suggest that not only highly prevalent areas but also those having at-risk movements from infected areas should be monitored. Pathogen management and surveillance options in the pig production sector should therefore take animal movements into consideration, paving the way for the development of targeted and risk-based disease surveillance strategies.


docid: inbnqrbi

title: Oscillation of SARS CoV-2 RNA load in a cohort of children and adolescents with neuro-psychiatric disorders resident in a nursing home of Lombardy Region (Italy).


title: Reverse transcription-loop-mediated isothermal amplification for the detection of rodent coronaviruses

text: Abstract Mouse hepatitis virus (MHV) is one of the most prevalent viruses detected in laboratory mouse colonies. Enterotropic strains predominate in natural infections, and molecular techniques for the detection of MHV shedding in feces are powerful enough to diagnose active infections. A reverse transcription-loop-mediated isothermal amplification (RT-LAMP) technique was developed for the detection of rodent coronaviruses within 90min. The specificity of this technique was confirmed by its ability to detect all 17 different strains of MHV and 6 strains of rat coronaviruses as well as its failure to detect human, bovine, and porcine coronaviruses nonspecifically. The sensitivity of RT-LAMP was 3.2-fold higher than that of reverse transcription-polymerase chain reaction (RT-PCR) and 31.6-fold lower than that of nested RT-PCR. An evaluation of the diagnostic performance of RT-LAMP performed in duplicate using mouse fecal specimens showed that the sensitivity and specificity with respect to nested RT-PCR were 85.7% and 100%, respectively. RT-LAMP assays would be suitable for monitoring active MHV infection in mouse colonies.


title: Traditional Chinese and Thai medicine in a comparative perspective

text: Abstract The work presented in this paper compares traditional Chinese medicine and traditional Thai medicine, expounding on origins, academic thinking, theoretical system, diagnostic method and modern development. Based on a secondary analysis of available literature, the paper concentrates on two crucial historical developments: (1) the response to, and consequences of, the impact of the Western medicine; and (2) the revival of traditional medicine in these two countries and its prospects. From a comparative perspective, the analysis has led to the conclusion that the rise and fall of traditional medicine is an issue closely related with social and political issues; and the development of traditional medicines requires national policy and financial support from governments, human resource development, the improvement of service quality, and the dissemination of traditional medicine knowledge to the public. In addition, this paper also suggests deepening exchanges and cooperation between China and Thailand, strengthening cooperation between traditional medicine and medical tourism.


title: Recent advances in the therapeutic applications of pyrazolines

text: Introduction: Pyrazolines are well-known and important nitrogen-containing five-membered ring heterocyclic compounds. Various methods have been worked out for their synthesis. Several pyrazoline derivatives have been found to possess diverse biological properties, which has stimulated research activity in this field. Areas covered: The present review sheds light on the recent therapeutic patent literature (2000 – 2011) describing the applications of pyrazolines and their derivatives on selected activities. Many of the therapeutic applications of pyrazoline derivatives have been discussed, either in the patent or in the general literature areas in this review. In addition to selected biological data, a wide range of pharmaceutical applications and pharmaceutical compositions are also summarized. Expert opinion: Pyrazoline derivatives have numerous prominent pharmacological effects, such as antimicrobial (antibacterial, antifungal, antiamoebic, antimycobacterial), anti-inflammatory, analgesic, antidepressant and anticancer. Further pharmacological effects include cannabinoid CB1 receptor antagonists, antiepileptic, antitrypanosomal, antiviral activity, MAO-inhibitory, antinociceptive activity, insecticidal, hypotensive, nitric oxide synthase inhibitor, antioxidant, steroidal and antidiabetic. Lastly, they also effect ACAT inhibition, urotensin II and somatostatin-5 receptors, TGF-β signal transduction inhibitors and neurocytotoxicity inhibitors activities. Many new pyrazoline derivatives have been synthesized and patented, but there are still new aspects to explore and work on.


title: The Impact of Matching Vaccine Strains and Post-SARS Public Health Efforts on Reducing Influenza-Associated Mortality among the Elderly

text: Public health administrators do not have effective models to predict excess influenza-associated mortality and monitor viral changes associated with it. This study evaluated the effect of matching/mismatching vaccine strains, type/subtype pattern changes in Taiwan's influenza viruses, and the impact of post-SARS (severe acute respiratory syndrome) public health efforts on excess influenza-associated mortalities among the elderly. A negative binomial model was developed to estimate Taiwan's monthly influenza-associated mortality among the elderly. We calculated three winter and annual excess influenza-associated mortalities [pneumonia and influenza (P&I), respiratory and circulatory, and all-cause] from the 1999–2000 through the 2006–2007 influenza seasons. Obtaining influenza virus sequences from the months/years in which death from P&I was excessive, we investigated molecular variation in vaccine-mismatched influenza viruses by comparing hemagglutinin 1 (HA1) of the circulating and vaccine strains. We found that the higher the isolation rate of A (H3N2) and vaccine-mismatched influenza viruses, the greater the monthly P&I mortality. However, this significant positive association became negative for higher matching of A (H3N2) and public health efforts with post-SARS effect. Mean excess P&I mortality for winters was significantly higher before 2003 than after that year [mean ± S.D.: 1.44±1.35 vs. 0.35±1.13, p = 0.04]. Further analysis revealed that vaccine-matched circulating influenza A viruses were significantly associated with lower excess P&I mortality during post-SARS winters (i.e., 2005–2007) than during pre-SARS winters [0.03±0.06 vs. 1.57±1.27, p = 0.01]. Stratification of these vaccine-matching and post-SARS effect showed substantial trends toward lower elderly excess P&I mortalities in winters with either mismatching vaccines during the post-SARS period or matching vaccines during the pre-SARS period. Importantly, all three excess mortalities were at their highest in May, 2003, when inter-hospital nosocomial infections were peaking. Furthermore, vaccine-mismatched H3N2 viruses circulating in the years with high excess P&I mortality exhibited both a lower amino acid identity percentage of HA1 between vaccine and circulating strains and a higher numbers of variations at epitope B. Our model can help future decision makers to estimate excess P&I mortality effectively, select and test virus strains for antigenic variation, and evaluate public health strategy effectiveness.


title: Occurrence and phylogenetic analysis of bovine respiratory syncytial virus in outbreaks of respiratory disease in Norway

text: BACKGROUND: Bovine respiratory syncytial virus (BRSV) is one of the major pathogens involved in the bovine respiratory disease (BRD) complex. The seroprevalence to BRSV in Norwegian cattle herds is high, but its role in epidemics of respiratory disease is unclear. The aims of the study were to investigate the etiological role of BRSV and other respiratory viruses in epidemics of BRD and to perform phylogenetic analysis of Norwegian BRSV strains. RESULTS: BRSV infection was detected either serologically and/or virologically in 18 (86%) of 21 outbreaks and in most cases as a single viral agent. When serology indicated that bovine coronavirus and/or bovine parainfluenza virus 3 were present, the number of BRSV positive animals in the herd was always higher, supporting the view of BRSV as the main pathogen. Sequencing of the G gene of BRSV positive samples showed that the current circulating Norwegian BRSVs belong to genetic subgroup II, along with other North European isolates. One isolate from an outbreak in Norway in 1976 was also investigated. This strain formed a separate branch in subgroup II, clearly different from the current Scandinavian sequences. The currently circulating BRSV could be divided into two different strains that were present in the same geographical area at the same time. The sequence variations between the two strains were in an antigenic important part of the G protein. CONCLUSION: The results demonstrated that BRSV is the most important etiological agent of epidemics of BRD in Norway and that it often acts as the only viral agent. The phylogenetic analysis of the Norwegian strains of BRSV and several previously published isolates supported the theory of geographical and temporal clustering of BRSV.


title: Coronavirus nucleocapsid proteins assemble constitutively in high molecular oligomers

text: Coronaviruses (CoV) are enveloped viruses and rely on their nucleocapsid N protein to incorporate the positive-stranded genomic RNA into the virions. CoV N proteins form oligomers but the mechanism and relevance underlying their multimerization remain to be fully understood. Using in vitro pull-down experiments and density glycerol gradients, we found that at least 3 regions distributed over its entire length mediate the self-interaction of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) N protein. The fact that these regions can bind reciprocally between themselves provides a possible molecular basis for N protein oligomerization. Interestingly, cytoplasmic N molecules of MHV-infected cells constitutively assemble into oligomers through a process that does not require binding to genomic RNA. Based on our data, we propose a model where constitutive N protein oligomerization allows the optimal loading of the genomic viral RNA into a ribonucleoprotein complex via the presentation of multiple viral RNA binding motifs.


title: The Nucleolus under Stress

text: Cells typically respond quickly to stress, altering their metabolism to compensate. In mammalian cells, stress signaling usually leads to either cell-cycle arrest or apoptosis, depending on the severity of the insult and the ability of the cell to recover. Stress also often leads to reorganization of nuclear architecture, reflecting the simultaneous inhibition of major nuclear pathways (e.g., replication and transcription) and activation of specific stress responses (e.g., DNA repair). In this review, we focus on how two nuclear organelles, the nucleolus and the Cajal body, respond to stress. The nucleolus senses stress and is a central hub for coordinating the stress response. We review nucleolar function in the stress-induced regulation of p53 and the specific changes in nucleolar morphology and composition that occur upon stress. Crosstalk between nucleoli and CBs is also discussed in the context of stress responses.


title: Mapping of the receptor-binding domain and amino acids critical for attachment in the spike protein of avian coronavirus infectious bronchitis virus

text: Abstract The infection of the avian coronavirus infectious bronchitis virus (IBV) is initiated by the binding of the spike glycoprotein S to sialic acids on the chicken host cell. In this study we identified the receptor-binding domain (RBD) of the spike of the prototype IBV strain M41. By analyzing the ability of recombinantly expressed chimeric and truncated spike proteins to bind to chicken tissues, we demonstrate that the N-terminal 253 amino acids of the spike are both required and sufficient for binding to chicken respiratory tract in an α-2,3-sialic acid-dependent manner. Critical amino acids for attachment of M41 spike are present within the N-terminal residues 19–69, which overlap with a hypervariable region in the S1 gene. Our results may help to understand the differences between IBV S1 genotypes and the ultimate pathogenesis of IBV in chickens.


title: COVID-19 and water

text: The 2019 coronavirus disease, called COVID-19, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since it was first identified in China in December 2019, COVID-19 has spread to almost all countries and territories and caused over 310,000 deaths, as on May 16, 2020. The impacts of the COVID-19 pandemic are now seen in almost every sector of our society. In this article, I discuss the impacts of COVID-19 on the water sector. I point out that our efforts to control the spread of COVID-19 will increase the water demand and worsen the water quality, leading to additional challenges in water planning and management. In view of the impacts of COVID-19 and other global-scale phenomena influencing water resources (e.g., global climate change), I highlight the urgent need for interdisciplinary collaborations among researchers studying water and new strategies to address water issues.


title: Immune response in cattle inoculated with the recombinant complete polyprotein of foot-and-mouth disease virus from Bombyx mori larvae

text: The intact open reading frame (ORF) of foot-and-mouth disease virus (FMDV) Asia I/XJ strain was amplified by RT-PCR and inserted into the transfer vector pVL1393 to generate plasmid pVL-ORF. Bm-N cells were transfected with pVL-ORF and linearized Bm-BacPAK6 DNA, and the recombinant silkworm baculovirus Bm-ORF containing the full ORF of FMDV was obtained. The results of indirect immunofluorescence assay (IFA) showed that Bm-ORF could be expressed efficiently in Bm-N cell. After inoculating the early 5th instar larvae of silkworm, the polyprotein of FMDV could be detected by sandwich ELISA and empty capsid-like particles could be observed under the electron microscope. Expression products from silkworm were used as the antigen to immunize the cattle. The specific antibody was induced in all vaccinated animals. The immunized cattle were challenged with the virulent FMDV Asia I/XJ strain, two of the four cattle were completely protected and clinical symptoms were alleviated and delayed in the others. The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.


Characterizing the Role of the “Triagist”: Reasons for Triage Discordance and Impact on Disposition


title: The potential impact of the COVID-19 response related lockdown on TB incidence and mortality in India

text: India has the highest burden of incident tuberculosis (TB) cases and deaths globally. TB is strongly associated with poverty and this risk is largely mediated by undernutrition in India. COVID-19 response related lockdown has resulted in an economic crisis which may double levels of poverty, has exacerbated food insecurity, and disrupted TB services. These developments may have serious implications for TB progression and transmission in India. The nutritional status of a population is a strong determinant of the TB incidence, and undernutrition in adults alone accounts for 32-44% of TB incidence in India. A systematic review has shown that a 14% increase in TB incidence can occur per one unit decrease in body mass index (BMI), across the BMI range of 18.5-30 kg/m2. We believe that one unit decrease in BMI (corresponding to a 2-3 kg weight loss) may result in the poor in India as a result of the lockdown and its aftermath. This may result in an increase in estimated (uncertainty interval) incident TB by 185 610 (180 230, 190 990) cases. A 59% reduction in TB case detection between end March and May 2020, may result in an estimated (uncertainty interval) additional 87 711 (59 998, 120 630) TB deaths [19.5% increase (14.5, 24.7)] in 2020. Disadvantaged social groups, those living in states with higher levels of poverty, undernutrition, and migrant workers are at particular risk. We suggest enhanced rations including pulses through the public distribution system, direct cash transfers to the poor pending restoration of livelihoods. TB services should be resumed immediately with enhanced efforts at case detection including active case finding. To prevent deaths among TB detected within the national TB programme, systemic identification, referral and management of severe disease at notification should be considered.


title: Stacking up the armory against viruses

text: Highlights of the Future Antiviral: Latest Developments in HIV, Hepatitis, Herpes, Influenza, RSV & SARS conference (12-13 November, 2003, London) discussing the major advances and novel solutions in the field of antiviral drug development.


title: Activation of Astrocytes in the Spinal Cord of Mice Chronically Infected with a Neurotropic Coronavirus

text: Abstract Mice infected with the neurotropic JHM strain of mouse hepatitis virus (MHV-JHM) develop a demyelinating encephalomyelitis several weeks after infection. Astrogliosis and infiltration of inflammatory cells are prominent findings in the brains and spinal cords of infected mice. In this report, astrocytes in infected spinal cords were analyzed for expression of three pleiotropic cytokines, TNF-α, IL-1β, and IL-6; Type 2 nitric oxide synthase (iNOS); and MHC class I and II antigen. The data show that all three cytokines and iNOS are expressed by astrocytes in chronically infected spinal cords. These activated astrocytes are localized to areas of virus infection and demyelination, although most of the astrocytes expressing these proteins are not MHV-infected. MHC class I and II antigen can be detected in these spinal cords as well, but not in cells with the typical morphology of astrocytes. TNF-α, IL-6, and iNOS are also evident in the brains of mice with MHV-induced acute encephalitis, but in marked contrast to the results obtained with the chronically infected mice, most of the cells expressing these cytokines or iNOS had the morphology of macrophages or other mononuclear cells and very few appeared to be astrocytes. Additionally, astrocytes and, most likely, oligodendrocytes are infected in the spinal cords of mice with chronic demyelination. These results are consistent with a role for both viral infection of glial cells and high localized levels of proinflammatory cytokines and nitric oxide in the demyelinating process in mice infected with MHV-JHM. They also show that analogously to the human demyelinating disease, multiple sclerosis, astrocytes are a major cellular source for these cytokines in mice with chronic, but not acute disease.


title: Immunopathogenesis of polymicrobial otitis media

text: OM, or inflammation of the middle ear, is a highly prevalent infection in children worldwide. OM is a multifactorial disease with multiple risk factors, including preceding or concurrent viral URT infection. Hence, OM is also a polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM are replete; however, all are predicated on the general principle of compromise of primary host airway defenses. Thus, despite an as-yet incomplete understanding of the molecular mechanisms involved in bacterial superinfection of a virus-compromised respiratory tract, the URT viruses are known to induce histopathology of airway mucosal epithelium, up-regulate expression of eukaryotic receptors used for bacterial adherence, alter the biochemical and rheological properties of airway mucus, and affect innate and acquired host immune functions, among others. Although discussed here in the context of OM, during preceding or concurrent viral infection of the human respiratory tract, viral impairment of airway defenses and the resulting predisposition to subsequent bacterial coinfection are also known to be operational in the mid and lower airway as well.


title: Potent neutralizing antibodies against SARS-CoV-2 identified by high-throughput single-cell sequencing of convalescent patients’ B cells

text: Summary The COVID-19 pandemic urgently needs therapeutic and prophylactic interventions. Here we report the rapid identification of SARS-CoV-2 neutralizing antibodies by high-throughput single-cell RNA and VDJ sequencing of antigen-enriched B cells from 60 convalescent patients. From 8,558 antigen-binding IgG1+ clonotypes, 14 potent neutralizing antibodies were identified with the most potent one, BD-368-2, exhibiting an IC50 of 1.2 ng/mL and 15 ng/mL against pseudotyped and authentic SARS-CoV-2, respectively. BD-368-2 also displayed strong therapeutic and prophylactic efficacy in SARS-CoV-2-infected hACE2-transgenic mice. Additionally, the 3.8Å Cryo-EM structure of a neutralizing antibody in complex with the spike-ectodomain trimer revealed the antibody’s epitope overlaps with the ACE2 binding site. Moreover, we demonstrated that SARS-CoV-2 neutralizing antibodies could be directly selected based on similarities of their predicted CDR3H structures to those of SARS-CoV neutralizing antibodies. Altogether, we showed that human neutralizing antibodies could be efficiently discovered by high-throughput single B-cell sequencing in response to pandemic infectious diseases.


title: COVID-19 spike-host cell receptor GRP78 binding site prediction

text: Summary Objectives Understanding the novel coronavirus (COVID-19) mode of host cell recognition may help to fight the disease and save lives. The spike protein of coronaviruses is the main driving force for host cell recognition. Methods In this study, the COVID-19 spike binding site to the cell-surface receptor (Glucose Regulated Protein 78 (GRP78)) is predicted using combined molecular modeling docking and structural bioinformatics. The COVID-19 spike protein is modeled using its counterpart, the SARS spike. Results Sequence and structural alignments show that four regions, in addition to its cyclic nature have sequence and physicochemical similarities to the cyclic Pep42. Protein-protein docking was performed to test the four regions of the spike that fit tightly in the GRP78 Substrate Binding Domain β (SBDβ). The docking pose revealed the involvement of the SBDβ of GRP78 and the receptor-binding domain of the coronavirus spike protein in recognition of the host cell receptor. Conclusions We reveal that the binding is more favorable between regions III (C391-C525) and IV (C480-C488) of the spike protein model and GRP78. Region IV is the main driving force for GRP78 binding with the predicted binding affinity of -9.8 kcal/mol. These nine residues can be used to develop therapeutics specific against COVID-19.


The inaugural Healthcare Infection Society Middle East Summit: a local perspective


title: Continuous monitoring of aerial bioburden within intensive care isolation rooms and identification of high-risk activities

text: Summary Background The spread of pathogens via the airborne route is often underestimated, and little is known about the extent to which airborne microbial contamination levels vary throughout the day and night in hospital facilities. Aims To evaluate airborne contamination levels within intensive care unit (ICU) isolation rooms over 10–24-h periods in order to improve understanding of the variability of environmental aerial bioburden, and the extent to which ward activities may contribute. Methods Environmental air monitoring was conducted within occupied and vacant inpatient isolation rooms. A sieve impactor sampler was used to collect 500-L air samples every 15 min over 10-h (08:00–18:00 h) and 24-h (08:00–08:00 h) periods. Samples were collected, room activity was logged, and bacterial contamination levels were recorded as colony-forming units (cfu)/m3 air. Findings A high degree of variability in levels of airborne contamination was observed across all scenarios in the studied isolation rooms. Air bioburden increased as room occupancy increased, with air contamination levels highest in rooms occupied for the longest time during the study (10 days) (mean 104.4 cfu/m3, range 12–510 cfu/m3). Counts were lowest in unoccupied rooms (mean 20 cfu/m3) and during the night. Conclusion Peaks in airborne contamination were directly associated with an increase in activity levels. This study provides the first clear evidence of the extent of variability in microbial airborne levels over 24-h periods in ICU isolation rooms, and found direct correlation between microbial load and ward activity.


title: Alpha-beta T cells provide protection against lethal encephalitis in the murine model of VEEV infection

text: We evaluated the safety and immunogenicity of a chimeric alphavirus vaccine candidate in mice with selective immunodeficiencies. This vaccine candidate was highly attenuated in mice with deficiencies in the B and T cell compartments, as well as in mice with deficient gamma-interferon responsiveness. However, the level of protection varied among the strains tested. Wild type mice were protected against lethal VEEV challenge. In contrast, alpha/beta (αβ) TCR-deficient mice developed lethal encephalitis following VEEV challenge, while mice deficient in gamma/delta ( γδ) T cells were protected. Surprisingly, the vaccine potency was diminished by 50% in animals lacking interferon-gamma receptor alpha chain (R1)-chain and a minority of vaccinated immunoglobulin heavy chain-deficient (μMT) mice survived challenge, which suggests that neutralizing antibody may not be absolutely required for protection. Prolonged replication of encephalitic VEEV in the brain of pre-immunized mice is not lethal and adoptive transfer experiments indicate that CD3(+) T cells are required for protection.


title: The Roles of Bacteria and Viruses in Bronchiectasis Exacerbation: A Prospective Study

text: Abstract Background Exacerbations are crucial events during bronchiectasis progression. Objectives To explore the associations between bacterial, viral, and bacterial plus viral isolations and bronchiectasis exacerbations. Methods In this prospective study, we enrolled 108 patients who were followed up every 3–6 months and at onset of exacerbations between March 2017 and November 2018. Spontaneous sputum was split for detection of bacteria (routine culture) and viruses (quantitative polymerase chain reaction). Symptoms and lung function were assessed during exacerbations. Results The median exacerbation rate was 2.0 (interquartile range: 1.0–2.5) per patient-year. At any visit, viral isolations (V+) occurred more frequently during onset of exacerbations [odds ratio (OR): 3.28, 95% confidence interval (95%CI): 1.76–6.12], as did isolation of new bacteria (NB+) (OR: 2.52, 95%CI: 1.35–4.71) and bacterial plus viral isolations (OR: 2.24, 95%CI: 1.11–4.55). Whilst coryza appeared more common in exacerbations with V+ than in exacerbations with no pathogen isolations and those with NB+, lower airway symptoms were more severe in exacerbations with NB+ (P <.05). Sputum interleukin-1β levels were higher in exacerbations with NB+ than in exacerbations with no pathogen isolations and those with V+ (both P <.05). Significantly more coryza symptoms correlated with bacterial plus viral isolations at exacerbations (P =.019). Compared with V+ alone, bacterial with and without viral isolations tended to yield more severe lower airway symptoms, but not sputum cytokine levels at exacerbations. Conclusions Viral isolations, isolation of new bacteria and bacterial plus viral isolation are associated with bronchiectasis exacerbations. Symptoms at exacerbations might inform clinicians the possible culprit pathogens.


title: Diagnosing COVID‐19 in the Emergency Department: A Scoping Review of Clinical Exam, Labs, Imaging Accuracy and Biases

text: In December 2019 a novel viral respiratory pathogen emerged in China, ultimately named severe acute respiratory syndrome coronavirus 2 (SARS‐Co‐V‐2) with the clinical illness dubbed coronavirus disease (COVID‐19). COVID‐19 became a global pandemic in early 2020 forcing governments worldwide to enact social isolation policies with dire economic ramifications. Emergency departments (ED) encountered decreased patient volumes before some in Seattle, New York City, New Orleans, and Detroit experienced waves of COVID‐19 patients mixed with asymptomatic patients or those concerned about potential exposures. Diagnosing COVID‐19 was hampered by inadequate supplies of reagents and kits, which was compounded by clinical and radiographic features that overlap with numerous seasonal viral respiratory infections.


MERS-CoV: in search of answers


title: Identification of the peptide derived from S1 domain that inhibits type I and type II feline infectious peritonitis virus infection

text: Abstract Feline infectious peritonitis virus (FIPV) can cause a lethal disease in cats, feline infectious peritonitis (FIP). A therapeutic drug that is effective against FIP has not yet been developed. Peptides based on viral protein amino acid sequences have recently been attracting attention as new antiviral drugs. In the present study, we synthesized 30 overlapping peptides based on the amino acid sequence of the S1 domain of the type I FIPV strain KU-2 S protein, and investigated their inhibitory effects on FIPV infection. To evaluate the inhibitory effects on type I FIPV infection of these peptides, we investigated a method to increase the infection efficiency of poorly replicative type I FIPV. The efficiency of type I FIPV infection was increased by diluting the virus with medium containing a polycation. Of the 30 peptides, I-S1-8 (S461-S480), I-S1-9 (S471-S490), I-S1-10 (S481-S500), I-S1-16 (S541-S560), and I-S1-22 (S601-S620) significantly decreased the infectivity of FIPV strain KU-2 while I-S1-9 and I-S1-16 exhibited marked inhibitory effects on FIPV infection. The inhibitory effects on FIPV infection of these 2 peptides on other type I and type II FIPV strains, feline herpesvirus (FHV), and feline calicivirus (FCV) were also examined. These 2 peptides specifically inhibited type I and type II FIPV, but did FHV or FCV infection. In conclusion, the possibility of peptides derived from the S protein of type I FIPV strain KU-2 as anti-FIPV agents effective not only for type I, but also type II FIPV was demonstrated in vitro.


title: Masters of disasters? Challenges and opportunities for SMEs in times of crisis

text: Small and medium-sized enterprises (SMEs) are the backbone of every economy. So, when an external crisis jeopardizes markets, such as the recent COVID-19 outbreak, SMEs are hit with great force. Their so-called liability of smallness, a lack of resources that would shield them from outside shocks, worsens the situation. This manuscript conducts a literature study on 69 manuscripts that studied SMEs in previous crises and proposes ways to overcome economic downturns in the areas of finance, strategy and the institutional environment. The paper finds a “strategy/funding chicken-and-egg-problem” and proposes an effectual world view when dealing with situations of great uncertainty.


title: Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus

text: Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.


title: Planning an innovation marathon at an infectious disease conference with results from the International Meeting on Emerging Diseases and Surveillance 2016 Hackathon

text: Abstract A hackathon is best described as an ‘innovation marathon’. Derived from the words ‘hacking’ and ‘marathon’, it brings together multidisciplinary teams to collaborate intensely over a short period of time to define a problem, devise a solution, and design a working prototype. International scientific meetings are conducive to successful hackathons, providing an audience of expert professionals who describe challenges and ensure the proposed solutions address end-user needs. Collaborations with local organizations and academic centers are crucial to attracting complementary specialties such as IT advisors, engineers, and entrepreneurs to develop sustainable projects. The core process of first identifying and deconstructing a problem followed by solution iteration is applicable to challenges at workplaces around the world. Ultimately, this model can be used to drive innovation and catalyze change in the global health community. The planning, execution, and outcomes of a hackathon event organized in conjunction with the International Meeting on Emerging Diseases and Surveillance (IMED 2016) are described in this article. Physicians, public health practitioners, veterinarians, IT professionals, engineers, and entrepreneurs came together for 2days to develop solutions at the intersection of emerging infectious diseases and climate change. Projects that resulted from the IMED 2016 Hackathon included environmental impact assessment software for humanitarian organization relief efforts; enhanced communication tools to prevent disease outbreaks; a participatory mobile application to speed the elimination of rabies in Indonesia; integrated disease surveillance platforms; and an improved search function for infectious disease outbreak reports in the ProMED-mail network.


title: DDX1 is an RNA-dependent ATPase Involved in HIV-1 Rev Function and Virus Replication

text: The HIV-1 Rev protein is essential for the virus because it promotes nuclear export of alternatively-processed mRNAs, and Rev is also linked to translation of viral mRNAs and genome encapsidation. Previously, the human DEAD-box helicase DDX1 was suggested to be involved in Rev functions, but this relationship is not well understood. Biochemical studies of DDX1 and its interactions with Rev and model RNA oligonucleotides were carried out to investigate the molecular basis for association of these components. A combination of gel-filtration chromatography and circular dichroism spectroscopy demonstrated that recombinant DDX1 expressed in E. coli is a well-behaved folded protein. Binding assays using fluorescently-labeled Rev and cell-based immunoprecipitation analysis confirmed a specific RNA-independent DDX1-Rev interaction. Additionally, DDX1 was shown to be an RNA-activated ATPase, wherein Rev-bound RNA was equally effective at stimulating ATPase activity as protein-free RNA. Gel mobility shift assays further demonstrated that DDX1 forms complexes with Rev-bound RNA. RNA silencing of DDX1 provided strong evidence that DDX1 is required for both Rev activity and HIV production from infected cells. Collectively, these studies demonstrate a clear link between DDX1 and HIV-1 Rev in cell based assays of HIV-1 production, and provide the first demonstration that recombinant DDX1 binds Rev and RNA, and has RNA dependent catalytic activity.


title: Characterization of trans- and cis-cleavage activity of the SARS coronavirus 3CL(pro) protease: basis for the in vitro screening of anti-SARS drugs

text: Severe acute respiratory syndrome (SARS) has been globally reported. A novel coronavirus (CoV), SARS-CoV, was identified as the etiological agent of the disease. SARS-CoV 3C-like protease (3CL(pro)) mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, playing an important role in viral replication. In this study, we demonstrated the expression of the SARS-CoV 3CL(pro) in Escherichia coli and Vero cells, and then characterized the in vitro trans-cleavage and the cell-based cis-cleavage by the 3CL(pro). Mutational analysis of the 3CL(pro) demonstrated the importance of His41, Cys145, and Glu166 in the substrate-binding subsite S1 for keeping the proteolytic activity. In addition, alanine substitution of the cleavage substrates indicated that Gln-(P1) in the substrates mainly determined the cleavage efficiency. Therefore, this study not only established the quantifiable and reliable assay for the in vitro and cell-based measurement of the 3CL(pro) activity, but also characterized the molecular interaction of the SARS-CoV 3CL(pro) with the substrates. The results will be useful for the rational development of the anti-SARS drugs.


title: Home Care for Cancer Patients During COVID-19 Pandemic: The Double Triage Protocol

text: Abstract Patients with cancer have an increased risk of developing severe forms of coronavirus disease 2019, and patients with advanced cancer who are followed at home represent a particularly frail population. Although with substantial differences, the challenges that cancer care professionals have to face during a pandemic are quite similar to those posed by natural disasters. We have already managed the oncological home care service in L’Aquila (middle Italy) after the 2009 earthquake. With this letter, we want to share the procedures and tools that we have started using at the home care service of the Tuscany Tumor Association during the coronavirus disease 2019 pandemic.


title: The New Normal: Key Considerations for Effective Serious Illness Communication Over Video or Telephone During the Coronavirus Disease 2019 (COVID-19) Pandemic

text: In-person communication with patients hospitalized with COVID-19 and their families is often not possible. This article provides helpful guidance on how to have meaningful conversations about serious illness using telecommunication.


title: The Search for Meaning in Virus Discovery

text: The rate of new virus discovery is increasing dramatically with improvements in sequencing and other molecular diagnostic platforms, and investments in sample collection and analysis. However, progress has been more limited in identification and implication of infectious agents that pose threats to human health and welfare. Here we review strategies for targeting research to enable efficient significant virus discovery.


title: Life-saving effect of convalescent plasma treatment in covid-19 disease: Clinical trial from eastern Anatolia

text: AIM: Convalescent Plasma (CP) therapy is of interest as no vaccine or specific treatment is available for emerging viruses such as severe acute respiratory syndrome coronavirus 2 causing Covid-19. It was aimed to report the results of our patients who underwent CP in the treatment of Covid-19. METHODS: CP treatment was applied to 26 Covid-19 patients in intensive care unit who had quantitative reverse transcriptase–polymerase chain reaction positive Sars-Cov-2 infection. Plasma was collected at least 14 days after complete recovery from patients who had mild or moderate infection with Sars-Cov-2 infection. The collected CP (200cc) were applied to severe Covid-19 patients. Laboratory values of patients just before CP and after 7 days were compared. RESULTS: There were no statistically significant differences in leukocyte, neutrophil, lymphocyte, platelet, CRP, ferritin, LDH, ALT, AST, sO(2) and total bilirubin values just before and after 1 week of CP. A statistically significant difference was found between age and lymphocyte values of living and dying patients. The patients who died were determined to have older age (74,6 vs 61,85, p = 0,018) and more severe lymphopenia (0,47 vs 1,18, p = 0,001). CONCLUSION: CP therapy has the potential to provide immediate and promising treatment options before specific vaccines and treatments are developed. In early stage Covid-19 patients who do not need mechanical ventilation, CP treatment may be a curative treatment option.


What further should be done to control COVID-19 outbreaks in addition to cases isolation and contact tracing measures?


title: The relevance of the aldehyde bisulfite toluidine blue reaction and its variants in the submicroscopic carbohydrate research

text: Summary Carbohydrates are chemical compounds that contain only oxygen, hydrogen and carbon. They are classified by their number of sugar units: monosaccharides (such as glucose and fructose), and disaccharides (such as sucrose and lactose) are simple carbohydrates; oligosaccharides and polysaccharides (such as starch, glycogen and cellulose) are complex carbohydrates. Carbohydrates play a crucial role in diverse biological systems [Hricovín M. Structural aspects of carbohydrates and the relation with their biological properties. Curr Med Chem 2004;11:2565–83]. According to Roseman [Sugars of the cell membrane. In: Weissmann G, Clairborn E, editors. Cell membranes. Biochemistry, Cell Biology, Pathology. New York: H. P. Publ. Co; 1975. p. 55–64], two classes of glycoproteins are described. Free glycoproteins are localised in the surface coat of the membranes and form a thick mobile layer, without any association to the membrane itself. Functionally, however, they are located in a close association with the membrane (e.g. in the duodenal mucosa). The other group consists of the membrane glycoproteins, which are integral to the membranes and are located in the outer layer. The oligosaccharide chains are bound to the N-terminal part of proteins, and are situated in the hydrophilic zone. Glycoproteins have diverse functions. They are important in specific receptor functions, in immunological cell destruction and play a significant role in reactions with lectins, antibodies, as well as in cell association and mutual recognition of the cells. This paper focuses on aspects of a summary of polarisation optical investigations and biological functions of the following three groups of carbohydrates: oligosaccharides, glycoproteins and glycosaminoglycans.


title: Advances in virtual screening

text: Although the term virtual screening as the in silico analog of high throughput screening has been coined only a decade ago, virtual screening is now a widespread lead identification method in the pharmaceutical industry. A myriad of different methods have been developed exploiting the growing library of target structures and assay data as a basis for finding new lead structures. Exploiting synergies between different methods best utilizes the information available and is at the center of recent developments. Section editors: Tudor Oprea – University of New Mexico, School of Medicine, Albuquerque, USA Alex Tropsha – University of North Carolina, Chapel Hill, USA


title: Emerging Infectious Diseases That Threaten the Blood Supply

text: Following the devastating effects of blood-transmitted human immunodeficiency virus (HIV), blood establishments have become increasingly vigilant for the emergence or re-emergence of new threats to the safety of the blood supply. Many agents have fulfilled the broad definition of emerging blood-transmitted infections, including West Nile virus (WNV), Trypanosoma cruzi, Plasmodium spp., Babesia spp., parvovirus B19, dengue virus, and the prions that cause variant Creutzfeld-Jacob disease (vCJD). Other agents such as human herpes virus- 8 (HHV-8—Kaposi’s sarcoma virus) and Borellia (Lyme disease) and, perhaps, avian flu virus, are known to have a viremic phase, but have not yet been proved to be transfusion-transmitted. In the wake of these threats, transfusion services use a variety of donor screening interventions, including serologic assays, nucleic acid assays, and geographic exclusions based on potential exposure. The ultimate safeguard may be a pre-emptive pathogen inactivation strategy that will disrupt all nucleic acid–containing agents (though not prions). Considerable effort and resources have been invested in this arena, but currently no single technique is effective for inactivation of both liquid and cellular blood products and toxicity issues have not been completely resolved. The blood supply is remarkably safe with the risk of major pathogens such as hepatitis C virus (HCV) and HIV now reduced to less than one transmission per 2 to 3 million exposures. However, to approach near-zero infectious disease risk for emerging and re-emerging pathogens, new strategies such as pathogen inactivation or multi-pathogen microarray technology will need to be developed or refined.


title: Immunohistochemical characterisation of PCV2 associate lesions in lymphoid and non-lymphoid tissues of pigs with natural postweaning multisystemic wasting syndrome (PMWS)

text: Abstract The lymphoid, renal, pulmonary, and hepatic lesions of naturally occurring postweaning multisystemic wasting syndrome (PMWS) affected pigs have been studied by means of immunohistology. Ten conventionally reared pigs showing acute clinical signs of PMWS were selected from a farm on which animal were seronegative to porcine reproductive and respiratory virus and to Aujeszky’s disease virus. All pigs were positive in tests for porcine circovirus type 2 by ISH and IHC. Monoclonal and polyclonal antibodies to CD3, CD79α, CD45RA (3C3/9), lysozyme, SLA-II-DQ (BL2H5), and MAC387 were used to characterise cells in PMWS lesions. The most relevant changes were reduction or loss of B and T lymphocytes, increased numbers of macrophages, and partial loss and redistribution of antigen presenting cells throughout lymphoid tissues compared to uninfected controls. The characteristics of lymphoid lesions in the present study strongly suggest an immunosuppressive effect of PMWS in affected pigs.


Influenza surveillance during 2015/2016 season in Portugal


title: Corticosteroids for community-acquired pneumonia: time to act!

text: The use of corticosteroids for the treatment of community-acquired pneumonia has been reported for almost 50 years. A recent systematic analysis of the relevant literature suggested that corticosteroids reduce the critical illness associated with community-acquired pneumonia. There is little doubt that a prolonged administration of a moderate dose of corticosteroids may alleviate the systemic inflammatory response and subsequent organ dysfunction in severe infection. Whether these favorable effects on morbidity may translate into better survival and quality of life needs to be addressed in additional adequately powered randomized controlled trials.


title: Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19

text: The SARS-CoV-2 is responsible for the pandemic COVID-19 in infected individuals, who can either exhibit mild symptoms or progress towards a life-threatening acute respiratory distress syndrome (ARDS). It is known that exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. With the aim to improve the knowledge in this area, we developed a cross-sectional study, in which we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood of COVID-19 patients with different clinical severity in comparison with healthy control individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Collectively, our results suggest that inflammatory transitional and non-classical monocytes preferentially migrate from blood to lungs in patients with severe COVID-19. CD1c+ conventional dendritic cells also followed this pattern, whereas CD141+ conventional and CD123hi plasmacytoid dendritic cells were depleted from blood but were absent in the lungs. Thus, this study increases the knowledge on the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies to fight SARS-CoV-2 infection.


COVID-19 and competition—aspiring for more than our old normality?


title: Elucidating Transmission Patterns From Internet Reports: Ebola and Middle East Respiratory Syndrome as Case Studies

text: The paucity of traditional epidemiological data during epidemic emergencies calls for alternative data streams to characterize the key features of an outbreak, including the nature of risky exposures, the reproduction number, and transmission heterogeneities. We illustrate the potential of Internet data streams to improve preparedness and response in outbreak situations by drawing from recent work on the 2014–2015 Ebola epidemic in West Africa and the 2015 Middle East respiratory syndrome (MERS) outbreak in South Korea. We show that Internet reports providing detailed accounts of epidemiological clusters are particularly useful to characterize time trends in the reproduction number. Moreover, exposure patterns based on Internet reports align with those derived from epidemiological surveillance data on MERS and Ebola, underscoring the importance of disease amplification in hospitals and during funeral rituals (associated with Ebola), prior to the implementation of control interventions. Finally, we discuss future developments needed to generalize Internet-based approaches to study transmission dynamics.


title: Quantitative Salivary Proteomic Differences in Oral Chronic Graft-versus-Host Disease

text: PURPOSE: Chronic graft-versus-host disease (cGVHD) is a severe immunological complication that occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Although oral cGVHD occurs in >25 % of cGVHD patients and leads to decreased quality of life, its etiology is poorly understood. The present retrospective cross-sectional analysis of oral cGVHD patients sought to (1) test the feasibility of liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify protein biomarkers of oral cGVHD and (2) to gain a clearer understanding of salivary proteins impacted by oral cGVHD. METHODS: Using unstimulated whole saliva, we compared pooled saliva from five patients with a diagnosis of moderate or severe oral cGVHD, with a gender-and age- matched pool of five cGVHD patients with no oral mucosal findings. LC-MS/MS was used to identify salivary proteins, followed by Ingenuity Pathway Analysis (IPA). Selected mass spectrometric findings, including lactotransferrin, lactoperoxidase, and albumin, were confirmed by targeted label-free quantification. RESULTS: LC-MS/MS led to confident identification of 180 proteins. Of these proteins, 102 changed in abundance at least 2 fold, including 12 proteins identified only in the No oral cGVHD group. Downregulation of ~0.4 fold was confirmed for both lactotransferrin and lactoperoxidase in Oral cGVHD saliva using targeted label-free quantification. IPA analysis implicated pathways involved in cellular metabolism and immunoregulation. CONCLUSIONS: Reduction of salivary lactoperoxidase, lactotransferrin, and several cysteine proteinase inhibitor family proteins suggests impaired oral antimicrobial host immunity in cGVHD patients. This shotgun proteomic analysis of oral cGVHD saliva using targeted label-free quantification of select proteins supports the use of mass spectrometry for future validation in a large patient population as noninvasive tests for screening, early detection, and monitoring of cGVHD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10875-012-9738-4) contains supplementary material, which is available to authorized users.


title: Le virus influenza, le SARS-CoV2 et les voies aériennes : mise au point pour l’Otorhinolaryngologiste

text: Résumé Le virus influenza et le SARS-CoV2 provoquent des infections respiratoires hautes banales et basses sévères (Virus influenza 290 000 à 650 000 décès/an). Ces virus entrent en contact avec les voies aériennes soit par projection directe, soit par inhalation secondaire de gouttelettes en suspension dans l’air, soit par manuportage. L’objectif de cet article est de faire une mise au point sur les mécanismes de production et de pénétration des gouttelettes de sécrétions, émises lors de tous les phénomènes expiratoires, susceptibles de transporter ces virus et venir au contact de la muqueuse respiratoire. Les gouttelettes > 5 µm suivent les lois de la balistique, celles < 5 µm suivent le mouvement Brownien et restent en suspension dans l’air. Les aérosols de gouttelettes sont hétérogènes que le sujet soit sain ou malade. En période infectieuse, les gouttelettes ne contiennent pas toutes de l’ARN viral. Si ces ARNs sont détectables autour des patients, sur les surfaces et dans l’air ambiant à des distances variables selon les études (de 0,5 m jusqu’au-delà de la chambre du patient) cela ne préjuge pas du caractère infectieux (viabilité) du virus et de la dose minimale infectieuse. Il y a un décalage entre la période de contagiosité et celle de la détection de l’ARN. Enfin, si des gouttelettes sont inhalées, elles devront suivre les lois de la dynamique des fluides (filtration) pour se déposer dans l’arbre respiratoire. Tout ceci explique pour partie la contagiosité et l’expression clinique de ces virus de la fente olfactive aux alvéoles pulmonaires.


title: Pneumonia Complicating Pregnancy

text: Community-acquired pneumonia (CAP) can affect pregnancy, posing risks to mother and fetus. CAP is the most common fatal nonobstetric infectious complication and a common cause of hospital readmission. Risk factors of pneumonia in pregnancy relate to anatomic and physiologic respiratory changes and immune changes. Aspiration can occur during labor, can cause life-threatening disease, and is more common in cesarean deliveries. Influenza pneumonia can cause severe disease, increasing the risk of preterm delivery, abortion, cesarean section, maternal respiratory failure, and death. CAP treatment requires considering antimicrobial appropriateness and safety, choosing therapy in line with guidelines, but considering maternal and fetal risk.


Considerations in Mandating a New Covid-19 Vaccine in the USA for Children and Adults


title: SARS-CoV fusion peptides induce membrane surface ordering and curvature

text: Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.


title: Medical Care for Undocumented Immigrants National and International Issues

text: The number of undocumented immigrants (UIs) varies worldwide, and most reside in the United States. With more than 12 million UIs in the United States, addressing the health care needs of this population presents unique challenges and opportunities. Most UIs are uninsured and rely on the safety-net health system for their care. Because of young age, this population is often considered to be healthier than the overall US population, but they have specific health conditions and risks. Adequate coverage is lacking; however, there are examples of how to better address the health care needs of UIs.


title: The VIZIER project: Preparedness against pathogenic RNA viruses

text: Abstract Life-threatening RNA viruses emerge regularly, and often in an unpredictable manner. Yet, the very few drugs available against known RNA viruses have sometimes required decades of research for development. Can we generate preparedness for outbreaks of the, as yet, unknown viruses? The VIZIER (VIral enZymes InvolvEd in Replication) (http://www.vizier-europe.org/) project has been set-up to develop the scientific foundations for countering this challenge to society. VIZIER studies the most conserved viral enzymes (that of the replication machinery, or replicases) that constitute attractive targets for drug-design. The aim of VIZIER is to determine as many replicase crystal structures as possible from a carefully selected list of viruses in order to comprehensively cover the diversity of the RNA virus universe, and generate critical knowledge that could be efficiently utilized to jump-start research on any emerging RNA virus. VIZIER is a multidisciplinary project involving (i) bioinformatics to define functional domains, (ii) viral genomics to increase the number of characterized viral genomes and prepare defined targets, (iii) proteomics to express, purify, and characterize targets, (iv) structural biology to solve their crystal structures, and (v) pre-lead discovery to propose active scaffolds of antiviral molecules.


title: Virus-induced vasculitis

text: There is a growing understanding of the different syndromes that have a definite, and in some cases a possible, association with viral infections. Hepatitis C virus-associated mixed cryoglobulinemias and hepatitis B virus-associated polyarteritis nodosa are examples of a vasculitis with a definite viral association. However, various types of cutaneous vasculitis are examples of a vasculitis with only a possible association with a viral infection.


title: Comparing ozone metrics on associations with outpatient visits for respiratory diseases in Taipei Metropolitan area

text: Abstract This study reported cumulative 6-day (lag 0–5 days) relative risks (RR) and confidence intervals (CI) of daily outpatient visits for total respiratory disease (RD), asthma, and chronic airway obstruction not otherwise classified (CAO) associated with three ozone metrics (daily 1-h maximum (O3, 1 h max), 8-h average maximum (O3, 8 h max), 24-h average (O3, 24 h avg)), and an alternative oxidant indicator (Ox) in Taipei Metropolitan, using distributed lag non-linear models after controlling for potential confounders. The Ox showed the strongest association with outpatient visits for total RD (RR = 1.10, 95% CI: 1.10, 1.11) and asthma (RR = 1.18, 95% CI: 1.00, 1.39) in the cold season. The O3, 24 h avg appeared to be the optimal ozone metric associating with total RD than O3, 1 h max and O3, 8 h max based on model selection. In conclusion, outpatient visits for total RD associated with ozone vary with ozone metrics, disease and season.


title: Campylobacteriosis, Salmonellosis, Yersiniosis, and Listeriosis as Zoonotic Foodborne Diseases: A Review

text: Zoonoses are diseases transmitted from animals to humans, posing a great threat to the health and life of people all over the world. According to WHO estimations, 600 million cases of diseases caused by contaminated food were noted in 2010, including almost 350 million caused by pathogenic bacteria. Campylobacter, Salmonella, as well as Yersinia enterocolitica and Listeria monocytogenes may dwell in livestock (poultry, cattle, and swine) but are also found in wild animals, pets, fish, and rodents. Animals, often being asymptomatic carriers of pathogens, excrete them with faeces, thus delivering them to the environment. Therefore, pathogens may invade new individuals, as well as reside on vegetables and fruits. Pathogenic bacteria also penetrate food production areas and may remain there in the form of a biofilm covering the surfaces of machines and equipment. A common occurrence of microbes in food products, as well as their improper or careless processing, leads to common poisonings. Symptoms of foodborne infections may be mild, sometimes flu-like, but they also may be accompanied by severe complications, some even fatal. The aim of the paper is to summarize and provide information on campylobacteriosis, salmonellosis, yersiniosis, and listeriosis and the aetiological factors of those diseases, along with the general characteristics of pathogens, virulence factors, and reservoirs.


title: Application of infrared thermography in computer aided diagnosis

text: Abstract The invention of thermography, in the 1950s, posed a formidable problem to the research community: What is the relationship between disease and heat radiation captured with Infrared (IR) cameras? The research community responded with a continuous effort to find this crucial relationship. This effort was aided by advances in processing techniques, improved sensitivity and spatial resolution of thermal sensors. However, despite this progress fundamental issues with this imaging modality still remain. The main problem is that the link between disease and heat radiation is complex and in many cases even non-linear. Furthermore, the change in heat radiation as well as the change in radiation pattern, which indicate disease, is minute. On a technical level, this poses high requirements on image capturing and processing. On a more abstract level, these problems lead to inter-observer variability and on an even more abstract level they lead to a lack of trust in this imaging modality. In this review, we adopt the position that these problems can only be solved through a strict application of scientific principles and objective performance assessment. Computing machinery is inherently objective; this helps us to apply scientific principles in a transparent way and to assess the performance results. As a consequence, we aim to promote thermography based Computer-Aided Diagnosis (CAD) systems. Another benefit of CAD systems comes from the fact that the diagnostic accuracy is linked to the capability of the computing machinery and, in general, computers become ever more potent. We predict that a pervasive application of computers and networking technology in medicine will help us to overcome the shortcomings of any single imaging modality and this will pave the way for integrated health care systems which maximize the quality of patient care.


title: The impact of 13-valent pneumococcal conjugate vaccination on virus-associated community-acquired pneumonia in elderly Exploratory analysis of the CAPiTA trial

text: Abstract Objectives Our objective was to evaluate whether vaccination with the 13-valent pneumococcal conjugate vaccine (PCV13) prevents the incidence of community-acquired pneumonia (CAP) caused by influenza (influenza-associated CAP, IA-CAP) or other respiratory viruses in the elderly. Methods This analysis was part of the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA); a double blind, randomized, placebo-controlled trial in 84 496 immunocompetent individuals aged ≥65 years. CAP was defined by clinical and radiological criteria, and oropharyngeal swabs were collected from all individuals referred to a sentinel centre with a clinical suspicion of pneumonia. Presence of influenza A and B, parainfluenza 1, 2, 3 and 4, human adeno-, boca-, corona-, metapneumo-, rhino- and respiratory syncytial viruses was determined by real-time PCR. Results Of 3209 episodes of suspected pneumonia, viral aetiology was tested in 2917 and proportions with influenza virus, human metapneumovirus and respiratory syncytial virus were 4.6%, 2.5% and 3.1%, respectively. There were 1653 oropharyngeal swabs for PCR testing available from 1814 episodes that fulfilled criteria for CAP, yielding 23 first episodes of IA-CAP in the PCV13 and 35 in the in placebo group—vaccine efficacy for IA-CAP of 34.4% (95% CI –11.1% to 61.2%; p 0.117). Annual influenza vaccination was received by 672 (87.2%) in the PCV13 group and 719 (87.7%) in the placebo group of the confirmed CAP cases. Conclusion In a randomized study of 84 496 elderly individuals with a high uptake of influenza vaccination, PCV13 was not associated with a statistically significant reduction of influenza or virus-associated CAP. Overall incidence of non-influenza viral pneumonia was low.


title: Chapter 4 Methods to Study Viruses

text: Abstract This chapter describes methods for growing, purifying, counting, and characterizing viruses. It also provides general principles of diagnostic virology. As obligate intracellular parasites, viruses require cell in which to replicate. The cells must express appropriate receptors and other proteins required by the virus. Cultured cells are often used to study basic steps in virus replication. Viruses can be purified away from cellular proteins and organelles using centrifugation techniques. Most viruses cannot be seen using standard light microscopes, but are often imaged using electron microscopy. Methods that combine image collection and computationally demanding image processing can provide incredible details about virus architecture. Another common way to visualize viruses is to use fluorescent tags or dyes. Although these techniques do not show detailed virus structures, they can be used to follow the progress of a virus through a cell and can provide a direct window into protein–protein interactions required for virus replication. A more indirect method to detect viruses is to look for virally induced changes to cell morphology. A variety of basic biochemical techniques are useful for analyzing viral proteins and nucleic acids. As the viral genomes are relatively simple, they can be manipulated/mutated to study the function of virtually any viral protein. Powerful genetic techniques can also be used to generate “designer” cells or organisms. There are a variety of methods for quantitating viruses. Infectivity assays measure the ability of a virus to productively infect a cell. Techniques that identify specific viral proteins or genomes provide ways to rapidly identify viruses. Some of these assays can be used at the bedside, or in the field. Powerful and inexpensive DNA sequencing technologies are being used to identify new viruses, many of which could not be found by other methods. The challenge is to understand how or if these viruses impact their hosts.


title: Antiproliferative effect of Toona sinensis leaf extract on non–small-cell lung cancer

text: Toona sinensis (TS), which is also known as Cedrela sinensis, belongs to Meliaceae family, the compounds identified from this TS leaves possess a wide range of biologic functions, such as hypoglycemic effects, anti–LDL glycative activity, antioxidant activities, and inhibition of sudden acute respiratory syndrome (SARS) coronavirus replication. However, their effect against cancer cells is not well explored. In this study, to understand the cytotoxic effect and molecular mechanism stimulated by TSL-1 (TS leaf extract fraction) we employed three different non–small-cell lung cancer (NSCLC) cell lines: H441 cells (lung adenocarcinoma), H661 cells (lung large cell carcinoma) and H520 cells (lung squamous cell carcinoma). IC50 value was varied between these three cell lines, the least IC50 value was observed in TSL-1–treated H661cells. Exposure of NSCLC cells to TSL-1 caused cell-cycle arrest in subG1 phase and caused apoptosis. Moreover, TSL-1 treatment decreased the cell-cycle regulators; cyclin D1 and CDK4 proteins by up regulating p27 expression in a dose-dependent manner. Thus, the TSL-1–induced apoptosis was further confirmed by cell morphology, subG1 peak accumulation, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) cleavage, propidium iodide (PI)-Annexin-V double staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The decreased Bcl2 protein level was concurrent with an increased Bax protein level in all 3 cell lines. Additionally, the tumoricidal effect of TSL-1 was measured using a xenograft model, after 5 weeks of TSL-1 treatment by various regimen caused regression of tumor. Taken together both these in vitro and in vivo studies revealed that TSL-1 is a potent inhibitor against NSCLC growth and our provoking result suggest that TSL-1 can be a better nutriceutical as a singlet or along with doublet agents (taxane, vinorelbine, and gemcitabine) for treating NSCLC.


title: Tanshinones as selective and slow-binding inhibitors for SARS-CoV cysteine proteases

text: Abstract In the search for anti-SARS-CoV, tanshinones derived from Salvia miltiorrhiza were found to be specific and selective inhibitors for the SARS-CoV 3CLpro and PLpro, viral cysteine proteases. A literature search for studies involving the seven isolated tanshinone hits showed that at present, none have been identified as coronaviral protease inhibitors. We have identified that all of the isolated tanshinones are good inhibitors of both cysteine proteases. However, their activity was slightly affected by subtle changes in structure and targeting enzymes. All isolated compounds (1–7) act as time dependent inhibitors of PLpro, but no improved inhibition was observed following preincubation with the 3CLpro. In a detail kinetic mechanism study, all of the tanshinones except rosmariquinone (7) were identified as noncompetitive enzyme isomerization inhibitors. However, rosmariquinone (7) showed a different kinetic mechanism through mixed-type simple reversible slow-binding inhibition. Furthermore, tanshinone I (5) exhibited the most potent nanomolar level inhibitory activity toward deubiquitinating (IC50 =0.7μM). Additionally, the inhibition is selective because these compounds do not exert significant inhibitory effects against other proteases including chymotrysin, papain, and HIV protease. These findings provide potential inhibitors for SARS-CoV viral infection and replication.


docid: reotxckr

title: The 9-kDa hydrophobic protein encoded at the 3′ end of the porcine transmissible gastroenteritis coronavirus genome is membrane-associated

text: Abstract The open reading frame potentially encoding a 78 amino acid, 9101 Da hydrophobic protein (HP) and, mapping at the 3′ end of the porcine transmissible gastroenteritis coronavirus (TGEV) genome, was shown to be expressed during virus replication. The cloned HP gene was placed in a plasmid under control of the T7 RNA polymerase promoter and in vitro translation of transcripts generated in vitro yielded a 9.1-kDa protein that was immunoprecipitable with porcine hyperimmune anti-TGEV serum. Antiserum raised in rabbits against a 31 amino acid synthetic polypeptide that represented the central hydrophilic region of HP specifically immunoprecipitated HP from TGEV-infected cells. HP was further shown to become associated with microsomal membranes during synthesis in vitro and was found to be closely associated with the endoplasmic reticulum and cell surface membranes in infected cells. The intracellular location of HP suggests that it may play a role in the membrane association of replication complexes or in virion assembly.


title: Recent insights into the development of therapeutics against coronavirus diseases by targeting N protein

text: The advent of severe acute respiratory syndrome (SARS) in the 21st century and the recent outbreak of Middle-East respiratory syndrome (MERS) highlight the importance of coronaviruses (CoVs) as human pathogens, emphasizing the need for development of novel antiviral strategies to combat acute respiratory infections caused by CoVs. Recent studies suggest that nucleocapsid (N) proteins from coronaviruses and other viruses can be useful antiviral drug targets against viral infections. This review aims to provide readers with a concise survey of the structural features of coronavirus N proteins and how these features provide insights into structure-based development of therapeutics against coronaviruses. We will also present our latest results on MERS-CoV N protein and its potential as an antiviral drug target.


docid: lythwgvt

title: Clinical evaluation of viral acute respiratory tract infections in children presenting to the emergency department of a tertiary referral hospital in the Netherlands

text: BACKGROUND: The relative incidence and clinical impact of individual respiratory viruses remains unclear among children presenting to the hospital emergency department with acute respiratory tract infection (ARTI). METHODS: During two winter periods, respiratory virus real-time multiplex PCR results were evaluated from children (< 18 years) presenting to the emergency department of a tertiary referral hospital with ARTI that had been sampled within 48 hours of hospital presentation. In an attempt to identify virus-specific distinguishing clinical features, single virus infections were correlated with presenting signs and symptoms, clinical findings and outcomes using multivariate logistic regression. RESULTS: In total, 274 children with ARTI were evaluated and most were aged < 3 years (236/274, 86%). PCR detected respiratory viruses in 224/274 (81.8%) children and included 162 (59%) single and 62 (23%) mixed virus infections. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) single virus infections were common among children aged < 3 years, but proportional differences compared to older children were only significant for RSV (95% CI 1.3–15). Clinical differentiation between viral ARTIs was not possible due to common shared presenting signs and symptoms and the high frequency of mixed viral infections. We observed virus-associated outcome differences among children aged < 3 years. Oxygen treatment was associated with RSV (OR 3.6) and inversely correlated with FLU (OR 0.05). Treatment with steroids (OR 3.4) or bronchodilators (OR 3.4) was associated with HRV. Severe respiratory complications were associated with HRV (OR 3.5) and inversely correlated with RSV (OR 0.24). CONCLUSIONS: Respiratory viruses are frequently detected in young children presenting to the hospital emergency department with ARTI and require PCR diagnosis since presenting signs and symptoms are not discriminant for a type of virus. RSV and HRV bear a high burden of morbidity in the pediatric clinical setting.


title: The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study

text: PURPOSE: In this prospective, multicenter, 14-day inception cohort study, we investigated the epidemiology, patterns of infections, and outcome in patients admitted to the intensive care unit (ICU) as a result of severe acute respiratory infections (SARIs). METHODS: All patients admitted to one of 206 participating ICUs during two study weeks, one in November 2013 and the other in January 2014, were screened. SARI was defined as possible, probable, or microbiologically confirmed respiratory tract infection with recent onset dyspnea and/or fever. The primary outcome parameter was in-hospital mortality within 60 days of admission to the ICU. RESULTS: Among the 5550 patients admitted during the study periods, 663 (11.9 %) had SARI. On admission to the ICU, Gram-positive and Gram-negative bacteria were found in 29.6 and 26.2 % of SARI patients but rarely atypical bacteria (1.0 %); viruses were present in 7.7 % of patients. Organ failure occurred in 74.7 % of patients in the ICU, mostly respiratory (53.8 %), cardiovascular (44.5 %), and renal (44.6 %). ICU and in-hospital mortality rates in patients with SARI were 20.2 and 27.2 %, respectively. In multivariable analysis, older age, greater severity scores at ICU admission, and hematologic malignancy or liver disease were independently associated with an increased risk of in-hospital death, whereas influenza vaccination prior to ICU admission and adequate antibiotic administration on ICU admission were associated with a lower risk. CONCLUSIONS: Admission to the ICU for SARI is common and associated with high morbidity and mortality rates. We identified several risk factors for in-hospital death that may be useful for risk stratification in these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00134-015-4206-2) contains supplementary material, which is available to authorized users.


title: A 15-year analysis of molecular epidemiology of avian infectious bronchitis coronavirus in China

text: Abstract A comprehensive study of the epidemiology and pathogenicity of infectious bronchitis virus (IBV) in China was carried out by molecular characterization of the S1 gene from 46 isolates obtained for this study and 174 reference strains isolated over a 15-year period. Nine types were found according to sequence analysis and phylogenetic study of the S1 gene. The co-circulation of multiple IBV types and the ongoing emergence of IBV variants are the epidemiological challenges in China. Factors contributing to the continual emergence include mutations, insertions and deletions in the S1 protein genes; recombination between local IBV strains circulating in chicken flocks in China; and recombination between local strains and vaccine strains. Vaccination-challenge analysis between circulating field strains and Mass-type H120 vaccine indicated the need to develop new vaccines from local IBV strains. These results also emphasize the importance of continued IBV surveillance in China.


title: Changing paradigms of dermatology practice in developing nations in the shadow of COVID‐19: Lessons learnt from the pandemic

text: At present, routine dermatology practices stay mostly disrupted worldwide owing to the ongoing COVID‐19 pandemic. However, dermatology services need to be resumed in future and dermatologists especially in developing countries face a mammoth task of devising plans to tackle the upcoming surge of patients while still maintaining the precautions to avoid risk of infection to health care workers and our patients. Teledermatology practice is a viable alternative and there is need of starting functioning teledermatology centers at primary health care centers and training health care workers in telemedicine. Several steps like increasing the working hours of outpatient clinics, posting dermatologists and health staffs in shifts, encouraging online registration and payment, providing time slots to patients should be taken to prevent overcrowding at outpatient departments in hospitals of developing countries like India where the usual patient turnover during summers maybe around 600 to 800 per day. Once diagnosed by the dermatologist, a subsequent meticulous use of teledermatology can limit the number of follow‐up visits. To avoid student gatherings, the undergraduate and postgraduate teaching schedule should be replaced by online or virtual teaching in form of webinars and video conferencing. Above all, intense upgradation of health care infrastructure, recruitment, training of new health care staffs on mass level and huge investment in health care sector is required in all the developing countries.


Resumption of elective surgery during the COVID-19 pandemic: what lessons can we apply?


title: Social Distancing During the COVID‐19 Pandemic: Who Are the Present and Future Non‐compliers?

text: Social distancing is an effective means for containing the spread of COVID‐19, but only so if we all participate. Who are the individuals who are the least likely to adhere to social distancing recommendations, presently and in the long‐term? Such knowledge is important for policymakers looking to sustain the public's buy‐in to social distancing. Using survey data from sample U.S. residents (n = 1,449), we show that some demographic factors (gender, age, race, political party) help predict intent to adhere to social distancing. Yet demographic factors are relatively poor predictors compared to individual attitudes and media diets. We argue that public officials should make efforts to inform and persuade the public of the importance of social distancing, targeting mediums like TV and radio where audiences are less likely to currently engage in social distancing or are less likely to envision themselves sustaining strict social distancing for several weeks or months. This article is protected by copyright. All rights reserved.


title: A hospital cluster combined with a family cluster of avian influenza H7N9 infection in Anhui Province, China

text: Summary Objectives To identify human-to-human transmission of H7N9 avian influenza virus, we investigated a hospital cluster combined with family cluster in this study. Methods We obtained and analyzed clinical, epidemiological and virological data from the three patients. RT-PCR, viral culture and sequencing were conducted for determination of causative pathogen. Results The index case presented developed pneumonia with fever after exposure to chicken in a poultry farm. Case A presented pneumonia with high fever on day 3 after she shared a hospital room with the index case. Case B, the father of the index case, presented pneumonia with high fever on day 15 after he took care of the index case. H7N9 virus circulated in the local farm to which the index case was exposed. Full genomic sequence of virus showed 99.8–100% identity shared between the index case and case A or case B. Compared to the earliest virus of Anhui, a total of 29 amino acid variation sites were observed in the 8 segments. Conclusions A hospital cluster combined with family cluster of H7N9 avian influenza infection was identified. Air transmission resulted in the hospital cluster possibly. A poultry farm was the initially infectious source of the cluster.