docid: suvmfqhn

title: Tropheryma whipplei in Children with Gastroenteritis

text: Tropheryma whipplei, which causes Whipple disease, is found in human feces and may cause gastroenteritis. To show that T. whipplei causes gastroenteritis, PCRs for T. whipplei were conducted with feces from children 2–4 years of age. Western blotting was performed for samples from children with diarrhea who had positive or negative results for T. whipplei. T. whipplei was found in samples from 36 (15%) of 241 children with gastroenteritis and associated with other diarrheal pathogens in 13 (33%) of 36. No positive specimen was detected for controls of the same age (0/47; p = 0.008). Bacterial loads in case-patients were as high as those in patients with Whipple disease and significantly higher than those in adult asymptomatic carriers (p = 0.002). High incidence in patients and evidence of clonal circulation suggests that some cases of gastroenteritis are caused or exacerbated by T. whipplei, which may be co-transmitted with other intestinal pathogens.


High-mobility group box 1 protein, angiotensins, ACE2, and target organ damage


title: Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty

text: PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.


title: Pegylated interferon-α protects type 1 pneumocytes against SARS coronavirus infection in macaques

text: The primary cause of severe acute respiratory syndrome (SARS) is a newly discovered coronavirus(1,2,3,4,5,6,7). Replication of this SARS coronavirus (SCV) occurs mainly in the lower respiratory tract, and causes diffuse alveolar damage(2,7,8). Lack of understanding of the pathogenesis of SARS has prevented the rational development of a therapy against this disease. Here we show extensive SCV antigen expression in type 1 pneumocytes of experimentally infected cynomolgus macaques (Macaca fascicularis) at 4 d postinfection (d.p.i.), indicating that this cell type is the primary target for SCV infection early in the disease, and explaining the subsequent pulmonary damage. We also show that prophylactic treatment of SCV-infected macaques with the antiviral agent pegylated interferon-α (IFN-α) significantly reduces viral replication and excretion, viral antigen expression by type 1 pneumocytes and pulmonary damage, compared with untreated macaques. Postexposure treatment with pegylated IFN-α yielded intermediate results. We therefore suggest that pegylated IFN-α protects type 1 pneumocytes from SCV infection, and should be considered a candidate drug for SARS therapy


title: Neutrophil to lymphocyte ratio as prognostic and predictive factor in patients with coronavirus disease 2019: A retrospective cross‐sectional study

text: This retrospective study was designed to explore whether neutrophil to lymphocyte ratio (NLR) is a prognostic factor in patients with coronavirus disease 2019 (COVID‐19). A cohort of patients with COVID‐19 admitted to the Tongren Hospital of Wuhan University from 11 January 2020 to 3 March 2020 was retrospectively analyzed. Patients with hematologic malignancy were excluded. The NLR was calculated by dividing the neutrophil count by the lymphocyte count. NLR values were measured at the time of admission. The primary outcome was all‐cause in‐hospital mortality. A multivariate logistic analysis was performed. A total of 1004 patients with COVID‐19 were included in this study. The mortality rate was 4.0% (40 cases). The median age of nonsurvivors (68 years) was significantly older than survivors (62 years). Male sex was more predominant in nonsurvival group (27; 67.5%) than in the survival group (466; 48.3%). NLR value of nonsurvival group (median: 49.06; interquartile range [IQR]: 25.71‐69.70) was higher than that of survival group (median: 4.11; IQR: 2.44‐8.12; P < .001). In multivariate logistic regression analysis, after adjusting for confounding factors, NLR more than 11.75 was significantly correlated with all‐cause in‐hospital mortality (odds ratio = 44.351; 95% confidence interval = 4.627‐425.088). These results suggest that the NLR at hospital admission is associated with in‐hospital mortality among patients with COVID‐19. Therefore, the NLR appears to be a significant prognostic biomarker of outcomes in critically ill patients with COVID‐19. However, further investigation is needed to validate this relationship with data collected prospectively.


title: Terapia génica: realidades actuales y expectativas

text: En esta revisión se describe la situación actual de la terapia génica en enfermedades hematológicas, inmunológicas y en cáncer. En todas ellas el objetivo principal de los diversos abordajes de la terapia génica es el transducir los genes terapéuticos en la mayor parte de las células diana. A nivel de enfermedades crónicas o inmunológicas se requiere, asimismo, una expresión estable de los genes terapéuticos y a nivel de las células tumorales la eficiencia o porcentaje de células transducidas condiciona el éxito de los tratamientos. Por consiguiente, los vectores son uno de los elementos básicos para optimizar los abordajes y protocolos de terapia génica dado que sabemos que con el empleo de liposomas menos del 10% de las células van a ser transducidas, que con el empleo de retrovirus sólo se van a infectar células en replicación y que con los adenovirus va a haber una respuesta inflamatoria importante y una transducción transitoria del gen terapéutico. Asimismo se discuten los últimos abordajes en terapia génica del cáncer con virus de replicación selectiva, genes suicidas, etc. In this review the current situation of gene therapy is described in hematological diseases, immunological conditions, and cancer. In all of them, the principal objective of various approaches with gene therapy is transduction of therapeutic genes in most of target cells. In chronic or immunological diseases, a stable expression of therapeutic genes is also required; in tumor cells, the efficiency or porcentage of transduced cells make conditional on the treatment success. Consequently, vectors are one of the basic elements to optimize gene therapy approaches and protocols in view of the facts that we know that with liposomes less than 10% of cells are transduced, that retrovirus only infect cells in replication, and that adenovirus give rise to an important inflammatory response and a transitory transduction of the therapeutic gene. In addition recent approaches in cancer gene therapy with selective replication virus, suicidal genes, etc., are discussed.


title: Infectious bronchitis virus from chickens in Al-Hasa, Saudi Arabia 2015-2016

text: AIM: This study aimed to isolate some of the currently circulating infectious bronchitis virus (IBV) strains from some broiler chicken farms in Al-Hasa and to do some molecular characteristics of these strains. MATERIALS AND METHODS: We collected 300 tissue specimens, including the trachea, bronchi, lungs, and kidneys from some four commercial chicken farms showing respiratory manifestations. We tested these tissue specimens by the real-time polymerase chain reaction (RT-PCR) and gel-based PCR. We selected some PCR positive samples for isolation in the embryonated chicken eggs (ECE). We sequenced some PCR-positive samples and conducted phylogenetic analysis based on the obtained sequences. RESULTS: Our molecular surveillance revealed that 31.6% of the tested specimens were IBV positive by PCR. We selected some positive specimens showing low Ct values by the qRT-PCR for virus isolation by the ECE. The infected eggs showed hemorrhage, dwarfing, and death in some cases after three passages in the ECE. We sequenced some of the positive PCR specimens and used the obtained sequences to draw the phylogenetic tree based on the partial IBV-ORF-1a, N, and S1 gene sequences. The phylogenetic trees based on the IBV-N and S1 gene sequences showed that the circulating IBV strains in Al-Hasa during 2016 was showing a high degree of identity to some strains from Taiwan and Italy. Meanwhile, the grouping of these strains based on the IBV-S1 sequences revealed that the currently circulating IBV strains in Al-Hasa belonged to Gr.I.7 along with strains from Taiwan. CONCLUSION: Our results confirmed the continuous circulation of the IBV among the chicken population in Al-Hasa despite the intensive application of vaccines against this virus.


title: Isolation of a novel Rhabdovirus from an insectivorous bat (Pipistrellus kuhlii) in Italy

text: BACKGROUND: Rhabdoviridae is one of the most ecologically diverse families of RNA viruses which can infect a wide range of vertebrates and invertebrates. Bats, among mammals, are pointed to harbor a significantly higher proportion of unknown or emerging viruses with zoonotic potential. Herein, we report the isolation of a novel rhabdovirus, detected in the framework of a virological survey on bats implemented in North Italy. METHODS: Virus isolation and identification were performed on samples of 635 bats by using cell cultures, negative staining electron microscopy and PCRs for different viruses. NGS was commonly performed on cell culture supernatants showing cytopathic effect or in case of samples resulted positive by at least one of the PCRs included in the diagnostic protocol. RESULTS: A rhabdovirus was isolated from different organs of a Pipistrellus kuhlii. Virus identification was obtained by electron microscopy and NGS sequencing. The complete genome size was 11,774 nt comprised 5 genes, encoding the canonical rhabdovirus structural proteins, and an additional transcriptional unit (U1) encoding a hypothetical small protein (157aa) (3’-N-P-M-G-U1-L-5′). The genome organization and phylogenetic analysis suggest that the new virus, named Vaprio virus (VAPV), belongs to the recently established genus Ledantevirus (subgroup B) and it is highly divergent to its closest known relative, Le Dantec virus (LDV) (human, 1965 Senegal). A specific RT-PCR amplifying a 350 bp fragment of the ORF 6 gene, encoding for L protein, was developed and used to test retrospectively a subset of 76 bats coming from the same area and period, revealing two more VAPV positive bats. CONCLUSIONS: VAPV is a novel isolate of chiropteran rhabdovirus. Genome organization and phylogenetic analyses demonstrated that VAPV should be considered a novel species within the genus Ledantevirus for which viral ecology and disease associations should be investigated.


title: Respiratory microbes present in the nasopharynx of children hospitalised with suspected pulmonary tuberculosis in Cape Town, South Africa

text: BACKGROUND: Lower respiratory tract infection in children is increasingly thought to be polymicrobial in origin. Children with symptoms suggestive of pulmonary tuberculosis (PTB) may have tuberculosis, other respiratory tract infections or co-infection with Mycobacterium tuberculosis and other pathogens. We aimed to identify the presence of potential respiratory pathogens in nasopharyngeal (NP) samples from children with suspected PTB. METHOD: NP samples collected from consecutive children presenting with suspected PTB at Red Cross Children’s Hospital (Cape Town, South Africa) were tested by multiplex real-time RT-PCR. Mycobacterial liquid culture and Xpert MTB/RIF was performed on 2 induced sputa obtained from each participant. Children were categorised as definite-TB (culture or qPCR [Xpert MTB/RIF] confirmed), unlikely-TB (improvement of symptoms without TB treatment on follow-up) and unconfirmed-TB (all other children). RESULTS: Amongst 214 children with a median age of 36 months (interquartile range, [IQR] 19–66 months), 34 (16 %) had definite-TB, 86 (40 %) had unconfirmed-TB and 94 (44 %) were classified as unlikely-TB. Moraxella catarrhalis (64 %), Streptococcus pneumoniae (42 %), Haemophilus influenzae spp (29 %) and Staphylococcus aureus (22 %) were the most common bacteria detected in NP samples. Other bacteria detected included Mycoplasma pneumoniae (9 %), Bordetella pertussis (7 %) and Chlamydophila pneumoniae (4 %). The most common viruses detected included metapneumovirus (19 %), rhinovirus (15 %), influenza virus C (9 %), adenovirus (7 %), cytomegalovirus (7 %) and coronavirus O43 (5.6 %). Both bacteria and viruses were detected in 73, 55 and 56 % of the definite, unconfirmed and unlikely-TB groups, respectively. There were no significant differences in the distribution of respiratory microbes between children with and without TB. Using quadratic discriminant analysis, human metapneumovirus, C. pneumoniae, coronavirus 043, influenza virus C virus, rhinovirus and cytomegalovirus best discriminated children with definite-TB from the other groups of children. CONCLUSIONS: A broad range of potential respiratory pathogens was detected in children with suspected TB. There was no clear association between TB categorisation and detection of a specific pathogen. Further work is needed to explore potential pathogen interactions and their role in the pathogenesis of PTB. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12879-016-1934-z) contains supplementary material, which is available to authorized users.


docid: jseyjnqg

title: Nonhuman Primate Models for SARS

text: Osterhaus and Haagmans discuss a new study in PLoS Medicine that supports the use of the cynomolgus macaque model to study SARS pathogenesis and to test intervention strategies.


title: The discrepant epidemiology of Middle East respiratory syndrome coronavirus (MERS-CoV)

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerged infection in humans affecting the Arabian Peninsula, Europe, and North Africa. The source and persistence of the infection in humans remains unknown. The aim of this paper was to apply a risk analysis approach to the epidemiology of MERS-CoV and to understand the source of ongoing infections. The epidemiology of MERS-CoV was reviewed and compared to SARS. Each observed feature of MERS-CoV epidemiology was summarized and fitted to either an epidemic or one of two sporadic scenarios (either animal or deliberate release). As of May 2014, MERS-CoV has infected over 681 people and killed a further 204 over 2 years. In contrast, there were 8,273 cases and 775 deaths from SARS within 8 months. MERS-CoV has a more sporadic pattern unlike the clear epidemic pattern seen with SARS, and an unusual concentration of cases in the Middle East, without epidemics in other countries to which it has spread. SARS, with a higher reproductive number (R0), was eliminated from humans within 8 months of emerging, yet MERS-CoV, with a low R0 has persisted in humans over a far more prolonged period. This is at odds with the expected behavior of a virus with a low R0, which theoretically should not persist unless there are ongoing introductions of infection into humans, and poses the question “what is the source of continuing infections in humans?” A hospital outbreak in Al Ahsa, the Kingdom of Saudi Arabia (KSA), had a classic epidemic pattern with some human-to-human transmission. However, 3 different strains were identified in that outbreak, an unexpected and unexplained finding for what appears to be a single source outbreak. Since this outbreak in April 2013, there has been a large increase in new cases, mainly in KSA in April and May 2014, with no corresponding epidemics in other countries. Yet MERS-CoV was present in KSA over several mass gatherings (which predispose to epidemics), including the Hajj pilgrimage, without an epidemic arising. Furthermore, although the virus has been identified in bats and camels, the mode of ongoing transmission to humans remains uncertain. Although some cases appear to be transmitted from human to human, and a few have animal or camel exposure, many cases have no history of contact with either animals or human cases. A high proportion of asymptomatic or otherwise undetected cases have been postulated as an explanation for the unusual epidemiology, yet active surveillance does not support this. When the observed data were fitted to different disease patterns, the features of MERS-CoV fit better with a sporadic pattern, with evidence for either deliberate release or an animal source. There are many discrepancies in the observed epidemiology of MERS-CoV, which better fits a sporadic than an epidemic pattern. Possible explanations of the unusual features of the epidemiology include human-to-human transmission with a large proportion of undetected cases; or sporadic ongoing infections from a non-human source; or a combination of both. Possible sources of ongoing sporadic infection in humans include animals (camels appear the most likely source), or deliberate release. The latter could explain 3 strains being present in a single hospital outbreak. Genetic testing should be conducted to determine whether the virus is evolving to be more transmissible. Better ascertainment of mild or asymptomatic cases is also needed. Finally, the discrepant epidemiology warrants critical analysis of all possible explanations, and involvement of all stakeholders in biosecurity, and deliberate release must be seriously considered and at least acknowledged as a possibility.


title: 31 Infection in Kidney Transplant Recipients

text: Abstract In organ transplant recipients, impaired inflammatory responses suppress the clinical and radiologic findings of infection. The possible etiologies of infection are diverse, ranging from common bacterial and viral pathogens that affect the entire community to opportunistic pathogens that cause invasive disease only in immunocompromised hosts. Antimicrobial therapies required to treat established infection are often complex, with accompanying risks for drug toxicities and drug interactions with the immunosuppressive agents used to maintain graft function. Rapid and specific diagnosis is essential for successful therapy. The risk of serious infections in the organ transplant patient is largely determined by the interaction between two factors: the patient’s epidemiologic exposures and the patient’s net state of immunosuppression. The epidemiology of infection includes environmental exposures and nosocomial infections, organisms derived from donor tissues, and latent infections from the recipient activated with immunosuppression. The net state of immune suppression is a conceptual framework that measures those factors contributing to risk for infection: the dose, duration, and temporal sequence of immunosuppressive drugs; the presence of foreign bodies or injuries to mucocutaneous barriers; neutropenia; metabolic abnormalities including diabetes; devitalized tissues, hematomas, or effusions postsurgery; and infection with immunomodulating viruses. Multiple factors are present in each host. A timeline exists to aid in the development of a differential diagnosis for infection. The timeline for each patient is altered by changes in prophylaxis and immunosuppressive drugs. For common infections, new microbiologic assays, often nucleic acid based, are useful in the diagnosis and management of opportunistic infections.


title: Public, environmental, and occupational health research activity in Arab countries: bibliometric, citation, and collaboration analysis

text: BACKGROUND: The objective of this study was to analyze quantity, assess quality, and investigate international collaboration in research from Arab countries in the field of public, environmental and occupational health. METHODS: Original scientific articles and reviews published from the 22 Arab countries in the category "public, environmental & occupational health" during the study period (1900 – 2012) were screened using the ISI Web of Science database. RESULTS: The total number of original and review research articles published in the category of "public, environmental & occupational health" from Arab countries was 4673. Main area of research was tropical medicine (1862; 39.85%). Egypt with 1200 documents (25.86%) ranked first in quantity and ranked first in quality of publications (h-index = 51). The study identified 2036 (43.57%) documents with international collaboration. Arab countries actively collaborated with authors in Western Europe (22.91%) and North America (21.04%). Most of the documents (79.9%) were published in public health related journals while 21% of the documents were published in journals pertaining to prevention medicine, environmental, occupational health and epidemiology. CONCLUSION: Research in public, environmental and occupational health in Arab countries is in the rise. Public health research was dominant while environmental and occupation health research was relatively low. International collaboration was a good tool for increasing research quantity and quality.


docid: xfmkczef

title: Cholesterol-Binding Viral Proteins in Virus Entry and Morphogenesis

text: Up to now less than a handful of viral cholesterol-binding proteins have been characterized, in HIV, influenza virus and Semliki Forest virus. These are proteins with roles in virus entry or morphogenesis. In the case of the HIV fusion protein gp41 cholesterol binding is attributed to a cholesterol recognition consensus (CRAC) motif in a flexible domain of the ectodomain preceding the trans-membrane segment. This specific CRAC sequence mediates gp41 binding to a cholesterol affinity column. Mutations in this motif arrest virus fusion at the hemifusion stage and modify the ability of the isolated CRAC peptide to induce segregation of cholesterol in artificial membranes. Influenza A virus M2 protein co-purifies with cholesterol. Its proton translocation activity, responsible for virus uncoating, is not cholesterol-dependent, and the transmembrane channel appears too short for integral raft insertion. Cholesterol binding may be mediated by CRAC motifs in the flexible post-TM domain, which harbours three determinants of binding to membrane rafts. Mutation of the CRAC motif of the WSN strain attenuates virulence for mice. Its affinity to the raft–non-raft interface is predicted to target M2 protein to the periphery of lipid raft microdomains, the sites of virus assembly. Its influence on the morphology of budding virus implicates M2 as factor in virus fission at the raft boundary. Moreover, M2 is an essential factor in sorting the segmented genome into virus particles, indicating that M2 also has a role in priming the outgrowth of virus buds. SFV E1 protein is the first viral type-II fusion protein demonstrated to directly bind cholesterol when the fusion peptide loop locks into the target membrane. Cholesterol binding is modulated by another, proximal loop, which is also important during virus budding and as a host range determinant, as shown by mutational studies.


title: Goal-Oriented Respiratory Management for Critically Ill Patients with Acute Respiratory Distress Syndrome

text: This paper, based on relevant literature articles and the authors' clinical experience, presents a goal-oriented respiratory management for critically ill patients with acute respiratory distress syndrome (ARDS) that can help improve clinicians' ability to care for these patients. Early recognition of ARDS modified risk factors and avoidance of aggravating factors during hospital stay such as nonprotective mechanical ventilation, multiple blood products transfusions, positive fluid balance, ventilator-associated pneumonia, and gastric aspiration can help decrease its incidence. An early extensive clinical, laboratory, and imaging evaluation of “at risk patients” allows a correct diagnosis of ARDS, assessment of comorbidities, and calculation of prognostic indices, so that a careful treatment can be planned. Rapid administration of antibiotics and resuscitative measures in case of sepsis and septic shock associated with protective ventilatory strategies and early short-term paralysis associated with differential ventilatory techniques (recruitment maneuvers with adequate positive end-expiratory pressure titration, prone position, and new extracorporeal membrane oxygenation techniques) in severe ARDS can help improve its prognosis. Revaluation of ARDS patients on the third day of evolution (Sequential Organ Failure Assessment (SOFA), biomarkers and response to infection therapy) allows changes in the initial treatment plans and can help decrease ARDS mortality.


An Outbreak of Severe Acute Respiratory Syndrome in a Nursing Home


title: Genetic sequence changes related to the attenuation of avian infectious bronchitis virus strain TW2575/98

text: The attenuated avian infectious bronchitis virus (IBV), derived from a wild strain (TW2575/98w) in chicken embryos after 75 passages, is designed as a commercial vaccine strain (TW2575/98vac) to control the disease in Taiwan. The differences in viral infectivity, replication efficiency, and genome sequences between TW2575/98w and TW2575/98vac were determined and compared. TW2575/98vac caused earlier death of chicken embryos and had higher viral replication efficiency. Thirty amino acid substitutions resulting from 44 mutated nucleotides in the viral genome were found in TW2575/98vac. All of the molecular variations lead to attenuation, found in TW2575/98, were not observed consistently in the other IBVs (TW2296/95, Ark/Ark-DPI/81, the Massachusetts strain, GA98/CWL0470/98, and CK/CH/LDL/97I) and vice versa. After further comparisons and evaluations from three aspects: (1) longitudinal analysis on the timing of variations appeared in specific homologous strain passages, (2) horizontal evaluations with the amino acid changes between wild and vaccine strains among the other 5 IBVs, and (3) inspection on alterations in the chemical characteristics of substituted amino acid residues in viral proteins, four amino acid substitutions [V342D in p87, S1493P and P2025S in HD1, as well as F2308Y in HD1(P41)] were selected as highly possible candidates for successful TW2575/98w attenuation. Our findings imply that molecular variations, which contribute to the successful attenuation of different IBVs, are diverse and not restricted to a fixed pattern or specific amino acid substitutions in viral proteins. In addition, four amino acid changes within the replicase gene-encoded proteins might be associated with TW2575/98 virus virulence. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11262-020-01753-5) contains supplementary material, which is available to authorized users.


title: Evaluation of recombinase polymerase amplification for detection of begomoviruses by plant diagnostic clinics

text: BACKGROUND: Plant viruses in the genus Begomovirus, family Geminiviridae often cause substantial crop losses. These viruses have been emerging in many locations throughout the tropics and subtropics. Like many plant viruses, they are often not recognized by plant diagnostic clinics due in large part to the lack of rapid and cost effective assays. An isothermal amplification assay, Recombinase polymerase amplification (RPA), was evaluated for its ability to detect three begomoviruses and for its suitability for use in plant diagnostic clinics. Methods for DNA extraction and separation of amplicons from proteins used in the assay were modified and compared to RPA manufacturer’s protocols. The modified RPA assays were compared to PCR assays for sensitivity, use in downstream applications, cost, and speed. RESULTS: Recombinase polymerase amplification (RPA) assays for the detection of Bean golden yellow mosaic virus, Tomato mottle virus and Tomato yellow leaf curl virus (TYLCV) were specific, only amplifying the target viruses in three different host species. RPA was able to detect the target virus when the template was in a crude extract generated using a simple inexpensive extraction method, while PCR was not. Separation of RPA-generated amplicons from DNA-binding proteins could be accomplished by several methods, all of which were faster and less expensive than that recommended by the manufacturer. Use of these modifications resulted in an RPA assay that was faster than PCR but with a similar reagent cost. This modified RPA was the more cost effective assay when labor is added to the cost since RPA can be performed much faster than PCR. RPA had a sensitivity approximate to that of ELISA when crude extract was used as template. RPA-generated amplicons could be used in downstream applications (TA cloning, digestion with a restriction endonuclease, direct sequencing) similar to PCR but unlike some other isothermal reactions. CONCLUSIONS: RPA could prove useful for the cost effective detection of plant viruses by plant diagnostic clinics. It can be performed in one hour or less with a reagent cost similar to that of PCR but with a lower labor cost, and with an acceptable level of sensitivity and specificity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12985-016-0504-8) contains supplementary material, which is available to authorized users.


title: Genomics and Proteomics of Mycobacteriophage Patience, an Accidental Tourist in the Mycobacterium Neighborhood

text: Newly emerging human viruses such as Ebola virus, severe acute respiratory syndrome (SARS) virus, and HIV likely originate within an extant population of viruses in nonhuman hosts and acquire the ability to infect and cause disease in humans. Although several mechanisms preventing viral infection of particular hosts have been described, the mechanisms and constraints on viral host expansion are ill defined. We describe here mycobacteriophage Patience, a newly isolated phage recovered using Mycobacterium smegmatis mc(2)155 as a host. Patience has genomic features distinct from its M. smegmatis host, including a much lower GC content (50.3% versus 67.4%) and an abundance of codons that are rarely used in M. smegmatis. Nonetheless, it propagates well in M. smegmatis, and we demonstrate the use of mass spectrometry to show expression of over 75% of the predicted proteins, to identify new genes, to refine the genome annotation, and to estimate protein abundance. We propose that Patience evolved primarily among lower-GC hosts and that the disparities between its genomic profile and that of M. smegmatis presented only a minimal barrier to host expansion. Rapid adaptions to its new host include recent acquisition of higher-GC genes, expression of out-of-frame proteins within predicted genes, and codon selection among highly expressed genes toward the translational apparatus of its new host.


title: Implementation of FilmArray Respiratory Viral Panel in a Core Laboratory Improves Testing Turnaround Time and Patient Care

text: The FilmArray respiratory virus panel detects 15 viral agents in respiratory specimens using polymerase chain reaction. We performed FilmArray respiratory viral testing in a core laboratory at a regional children’s hospital that provides service 24 hours a day 7 days a week. The average and median turnaround time were 1.6 and 1.4 hours, respectively, in contrast to 7 and 6.5 hours documented 1 year previously at an on-site reference laboratory using a direct fluorescence assay (DFA) that detected 8 viral agents. During the study period, rhinovirus was detected in 20% and coronavirus in 6% of samples using FilmArray; these viruses would not have been detected with DFA. We followed 97 patients with influenza A or influenza B who received care at the emergency department (ED). Overall, 79 patients (81%) were given oseltamivir in a timely manner defined as receiving the drug in the ED, a prescription in the ED, or a prescription within 3 hours of ED discharge. Our results demonstrate that molecular technology can be successfully deployed in a nonspecialty, high-volume, multidisciplinary core laboratory.


title: Why have youth physical activity trends flatlined in the last decade? – Opinion piece on “Global trends in insufficient physical activity among adolescents: a pooled analysis of 298 population-based surveys with 1.6 million participants” by Guthold et al.

text: • Globally physical inactivity rates in school-going adolescents are alarming. • Using realist and co-creation methodologies to better understand and develop multisectoral strategies and programs and efforts to promote effective uptake of evidence-based programs into routine practice at scale are urgently needed.


docid: pkkpdpcf

title: Targeting Antigens to Dendritic Cell Receptors for Vaccine Development

text: Dendritic cells (DCs) are highly specialized antigen presenting cells of the immune system which play a key role in regulating immune responses. Depending on the method of antigen delivery, DCs stimulate immune responses or induce tolerance. As a consequence of the dual function of DCs, DCs are studied in the context of immunotherapy for both cancer and autoimmune diseases. In vaccine development, a major aim is to induce strong, specific T-cell responses. This is achieved by targeting antigen to cell surface molecules on DCs that efficiently channel the antigen into endocytic compartments for loading onto MHC molecules and stimulation of T-cell responses. The most attractive cell surface receptors, expressed on DCs used as targets for antigen delivery for cancer and other diseases, are discussed.


title: Hematological and Biochemical Factors Predicting SARS Fatality in Taiwan

text: Background/Purpose Severe acute respiratory syndrome (SARS) has a high fatality rate worldwide. We examined the epidemiologic and clinical factors associated with death for all laboratory-confirmed SARS patients in Taiwan. Methods Using initial data in medical records reported by hospitals to the Center for Disease Control in Taiwan, we analyzed whether hematological, biochemical and arterial blood gas measures could predict fatality in 346 SARS patients. Results Both fatalities (n = 73; 21.1%) and survivors had elevated plasma concentration of initial C-reactive protein (CRP), but the mean CRP concentration was higher in fatalities (47.7 ± 43.3 mg/L) than in survivors (24.6 ± 28.2 mg/L). Initial lymphocyte counts were low in both fatalities (814 ± 378/μL) and survivors (1019 ± 480/μL). After controlling for age and sex, multiple logistic regression analysis showed that hematological factors significantly associated with fatality included initial neutrophil count > 7000/μL (odds ratio [OR] = 6.4), initial CRP concentration > 47.5 mg/L (OR = 5.8) and lactic acid dehydrogenase (LDH) > 593.5 IU/L (OR = 4.2). Factors significantly associated with initial CRP concentration > 47.5 mg/L included dyspnea (OR = 4.3), red blood cell count < 4.1 × 106/μL (OR = 4.3) and serum aspartate amino-transferase > 57 IU/L (OR = 3.1). Conclusion Initial neutrophil count, CRP and LDH levels are important predictors of mortality from SARS. [J Formos Med Assoc 2006;105(6):439-450]


title: Synthesis and biological evaluation of 2-(5-substituted-1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-substituted-hydrazinecarbothioamides

text: ABSTRACT: Various 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (4a, b) and 5-substituted-2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(phenyl-4-substituted)hydrazinecarbothioamide (5a–h) derivatives were synthesized. The compounds were screened for cytotoxicity against human HeLa and CEM T-lymphocytes as well as murine L1210 cells. The compounds were also screened for β-lactamase inhibitory activity, antiviral, antibacterial, and antifungal activity against various strains of microorganisms. Several of these compounds were endowed with low micromolar 50 %-cytostatic concentration (IC(50)) values, and some were virtually equally potent as melphalan. The most potent inhibitors against the murine leukemia cells (L1210) were also the most inhibitory against human T-lymphocyte (CEM) tumor cells. Derivative 2-(1-((diethylamino)methyl)-2-oxoindolin-3-ylidene)-N-(4-methoxyphenyl)hydrazinecarbothioamide 5c emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC(50) 11–20 μM). Moderate antimicrobial activity was observed for all derivatives. The encouraging cytostatic and antiviral activity data provide an adequate rationale for further modification of these molecular scaffolds. GRAPHICAL ABSTRACT: Derivative 5c (1.9–4.4 μM) emerged as the most potent cytostatic compound among the tested compounds. Derivatives 4b, 5a, 5b, and 5d showed antiviral activity against HEL cell cultures (IC(50) 11–20 μM). [Image: see text]


title: Silver nanoparticles for delivery purposes

text: The synthesis of nanostructured materials can be considered a research field of high importance, especially in the recent past, due to the unique properties that make these materials applicable in different fields of science and technology. Metallic nanoparticles gained significant interest due to the possibility to obtain them through biological means, among other techniques. Silver nanoparticles are some of the most investigated metallic nanoparticles, due to their recognized anticancer, antimicrobial, and antiviral potential. This chapter aims to summarize the emerging efforts to address current challenges and solutions in the treatment of infectious diseases, particularly through the use of silver nanoparticles biosynthesized via microbes and plants pathways.


title: Capture-stabilize approach for membrane protein SPR assays

text: Measuring the binding kinetics of antibodies to intact membrane proteins by surface plasmon resonance has been challenging largely because of the inherent difficulties in capturing membrane proteins on chip surfaces while retaining their native conformation. Here we describe a method in which His-tagged CXCR5, a GPCR, was purified and captured on a Biacore chip surface via the affinity tag. The captured receptor protein was then stabilized on the chip surface by limited cross-linking. The resulting chip surface retained ligand binding activity and was used for monoclonal antibody kinetics assays by a standard Biacore kinetics assay method with a simple low pH regeneration step. We demonstrate the advantages of this whole receptor assay when compared to available peptide-based binding assays. We further extended the application of the capture-stabilize approach to virus-like particles and demonstrated its utility analyzing antibodies against CD52, a GPI-anchored protein, in its native membrane environment. The results are the first demonstration of chemically stabilized chip surfaces for membrane protein SPR assays.


title: Suppression of NF-κB Activity: A Viral Immune Evasion Mechanism

text: Nuclear factor-κB (NF-κB) is an important transcription factor that induces the expression of antiviral genes and viral genes. NF-κB activation needs the activation of NF-κB upstream molecules, which include receptors, adaptor proteins, NF-κB (IκB) kinases (IKKs), IκBα, and NF-κB dimer p50/p65. To survive, viruses have evolved the capacity to utilize various strategies that inhibit NF-κB activity, including targeting receptors, adaptor proteins, IKKs, IκBα, and p50/p65. To inhibit NF-κB activation, viruses encode several specific NF-κB inhibitors, including NS3/4, 3C and 3C-like proteases, viral deubiquitinating enzymes (DUBs), phosphodegron-like (PDL) motifs, viral protein phosphatase (PPase)-binding proteins, and small hydrophobic (SH) proteins. Finally, we briefly describe the immune evasion mechanism of human immunodeficiency virus 1 (HIV-1) by inhibiting NF-κB activity in productive and latent infections. This paper reviews a viral mechanism of immune evasion that involves the suppression of NF-κB activation to provide new insights into and references for the control and prevention of viral diseases.


title: COVID-19 Impact on Stroke Presentations

text: BACKGROUND: As Covid-19 evolved into a world-wide pandemic, hospitals reported marked declines in strokes, only to be followed by reports of increased numbers of young people presenting with large-vessel occlusions. We reviewed our patient data-base to determine if similar or other novel trends were present. RESULTS: Our Thrombectomy Stroke Center experienced marked declines in ED visits from 2,349 in early March to 1,178 in late April, stroke alerts dropped from 34 to 14 during the same period. Average monthly stroke admissions dropped from 34 in 2019 to 23 in 2020. Nonetheless, in March, we had 12 patients eligible for tPA, which is twice the typical caseload and was unexpected given the low overall stroke presentations. Although the neurointervention caseload was low, the patients were significantly younger. Of the acute intervention patients in March, 5 of the 12 patients were ≤ 60 years old, and two were in their 30’s. These trends are similar to those reported elsewhere but were highly unusual for our center as our catchment area is predominantly Caucasian with 45% of the population > 65 years of age. CONCLUSIONS: Even in low risk centers Covid-19 will likely impart unique stroke presentations. It will be imperative to determine the mechanisms responsible for these changes so we can institute effective strategies for optimal stroke prevention as well as maintain timely acute interventions.


docid: gfzobzrg

title: Considerations for Postacute Rehabilitation for Survivors of COVID-19

text: Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question “What rehabilitation services do survivors of COVID-19 require?” The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.


title: Cross-infection and infection control in dentistry: Knowledge, attitude and practice of patients attended dental clinics in King Abdulaziz University Hospital, Jeddah, Saudi Arabia

text: Abstract The objective of the study was to determine the level of Knowledge, Attitude and Practice (KAP) of patients attended dental clinics at King Abdulaziz University Hospital (KAUH) regarding cross infections and infection control in dentistry. A cross-sectional study was conducted among 225 patients who attended the dental clinics of KAUH, Jeddah, Saudi Arabia, 2014. A standardized, confidential, anonymous, interviewing questionnaire was used. Knowledge about dental infections was assessed by 12 MCQs. The attitudes were assessed through answering seven statements on a three- point Likert scale. Patients’ self reported practices were also evaluated. Descriptive and inferential statistics were done. Results of the study revealed that 39.5%, 38.7% and 21.8% of the participants obtained poor, fair and satisfactory level of knowledge about infections and infection control in dentistry, respectively. Social media was the commonest source of information about dental infection. Participant's educational level was significantly associated with the level of knowledge about dental infection. Patients had positive attitudes towards infection control in dentistry. Regarding self-reported practice, only few participants would ask dentists about sterilization of dental instruments (9.3%), wearing face mask (13.3%) and gloves (16.4%) if they don’t do so. In conclusion, our participants had good attitudes towards infection control in dentistry. However, their knowledge and practice need improvements. Conduction of educational programs is needed through social media, mass media, schools and public places. These programs involve both patients and providers.


title: Solid-phase partitioning and release-retention mechanisms of copper, lead, zinc and arsenic in soils impacted by artisanal and small-scale gold mining (ASGM) activities

text: Artisanal and small-scale gold mining (ASGM) operations are major contributors to the Philippines’ annual gold (Au) output (at least 60%). Unfortunately, these ASGM activities lacked adequate tailings management strategies, so contamination of the environment is prevalent. In this study, soil contamination with copper (Cu), lead (Pb), zinc (Zn) and arsenic (As) in Nabunturan, Davao de Oro, Philippines due to ASGM activities was investigated. The results showed that ASGM-impacted soils had Cu, Pb, Zn and As up to 3.6, 83, 73 and 68 times higher than background levels, respectively and were classified as ‘extremely’ polluted (CD = 30–228; PLI = 5.5–34.8). Minerals typically found in porphyry copper-gold ores like pyrite, chalcopyrite, malachite, galena, sphalerite and goethite were identified by XRD and SEM-EDS analyses. Furthermore, sequential extraction results indicate substantial Cu (up to 90%), Pb (up to 50%), Zn (up to 65%) and As (up to 48%) were partitioned with strongly adsorbed, weak acid soluble, reducible and oxidisable fractions considered as ‘geochemically mobile’ phases in the environment. Although very high Pb and Zn were found in ASGM-impacted soils, they were relatively immobile under oxidising conditions around pH 8.5 because of their retention via adsorption to hydrous ferric oxides (HFOs), montmorillonite and kaolinite. In contrast, Cu and As release from the historic ASGM site samples exceeded the environmental limits for Class A and Class C effluents, which could be attributed to the removal of calcite and dolomite by weathering. The enhanced desorption of As at around pH 8.5 also likely contributed to its release from these soils.


title: Conserved antigenic sites between MERS-CoV and Bat-coronavirus are revealed through sequence analysis

text: BACKGROUND: MERS-CoV is a newly emerged human coronavirus reported closely related with HKU4 and HKU5 Bat coronaviruses. Bat and MERS corona-viruses are structurally related. Therefore, it is of interest to estimate the degree of conserved antigenic sites among them. It is of importance to elucidate the shared antigenic-sites and extent of conservation between them to understand the evolutionary dynamics of MERS-CoV. RESULTS: Multiple sequence alignment of the spike (S), membrane (M), enveloped (E) and nucleocapsid (N) proteins was employed to identify the sequence conservation among MERS and Bat (HKU4, HKU5) coronaviruses. We used various in silico tools to predict the conserved antigenic sites. We found that MERS-CoV shared 30 % of its S protein antigenic sites with HKU4 and 70 % with HKU5 bat-CoV. Whereas 100 % of its E, M and N protein’s antigenic sites are found to be conserved with those in HKU4 and HKU5. CONCLUSION: This sharing suggests that in case of pathogenicity MERS-CoV is more closely related to HKU5 bat-CoV than HKU4 bat-CoV. The conserved epitopes indicates their evolutionary relationship and ancestry of pathogenicity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13029-016-0049-7) contains supplementary material, which is available to authorized users.


title: Global wildlife trade permeates the Tree of Life

text: Legal and illegal wildlife trade is a multibillion dollar industry that is driving several species toward extinction. Even though wildlife trade permeates the Tree of Life, most analyses to date focused on the trade of a small selection of charismatic vertebrate species. Given that vertebrate taxa represent only 3% of described species, this is a significant bias that prevents the development of comprehensive conservation strategies. In this short contribution, we discuss the significance of global wildlife trade considering the full diversity of organisms for which data are available in the IUCN database. We emphasize the importance of being fast and effective in filling the knowledge gaps about non-vertebrate life forms, in order to achieve an in-depth understanding of global trading patterns across the full canopy of the Tree of Life, and not just its most appealing twig.


title: Antiviral Activity of Isatis indigotica Extract and Its Derived Indirubin against Japanese Encephalitis Virus

text: Isatis indigotica is widely used in Chinese Traditional Medicine for clinical treatment of virus infection, tumor, and inflammation, yet its antiviral activities remain unclear. This study probed antiviral activity of I. indigotica extract and its marker compounds against Japanese encephalitis virus (JEV). I. indigotica methanol extract, indigo, and indirubin proved less cytotoxic than other components, showing inhibitory effect (concentration-dependent) on JEV replication in vitro. Time-of-addition experiments proved the extract, indigo, and indirubin with potent antiviral effect by pretreatment (before infection) or simultaneous treatment (during infection), but not posttreatment (after entry). Antiviral action of these agents showed correlation with blocking virus attachment and exhibited potent virucidal activity. In particular, indirubin had strong protective ability in a mouse model with lethal JEV challenge. The study could yield anti-JEV agents.


title: Kanyawara Virus: A Novel Rhabdovirus Infecting Newly Discovered Nycteribiid Bat Flies Infesting Previously Unknown Pteropodid Bats in Uganda

text: Bats are natural reservoir hosts of highly virulent pathogens such as Marburg virus, Nipah virus, and SARS coronavirus. However, little is known about the role of bat ectoparasites in transmitting and maintaining such viruses. The intricate relationship between bats and their ectoparasites suggests that ectoparasites might serve as viral vectors, but evidence to date is scant. Bat flies, in particular, are highly specialized obligate hematophagous ectoparasites that incidentally bite humans. Using next-generation sequencing, we discovered a novel ledantevirus (mononegaviral family Rhabdoviridae, genus Ledantevirus) in nycteribiid bat flies infesting pteropodid bats in western Uganda. Mitochondrial DNA analyses revealed that both the bat flies and their bat hosts belong to putative new species. The coding-complete genome of the new virus, named Kanyawara virus (KYAV), is only distantly related to that of its closest known relative, Mount Elgon bat virus, and was found at high titers in bat flies but not in blood or on mucosal surfaces of host bats. Viral genome analysis indicates unusually low CpG dinucleotide depletion in KYAV compared to other ledanteviruses and rhabdovirus groups, with KYAV displaying values similar to rhabdoviruses of arthropods. Our findings highlight the possibility of a yet-to-be-discovered diversity of potentially pathogenic viruses in bat ectoparasites.


title: Management of muscle-invasive bladder cancer during a pandemic: Impact of treatment delay on survival outcomes for patients treated with definitive concurrent chemoradiation

text: INTRODUCTION: During the COVID-19 pandemic, providers and patients must engage in shared decision-making to ensure that the benefit of early intervention for muscle-invasive bladder cancer (MIBC) exceeds the risk of contracting COVID-19 in the clinic setting. It is unknown whether treatment delays for MIBC patients eligible for curative chemoradiation (CRT) compromise long-term outcomes. PATIENTS AND METHODS: In this study, we used the National Cancer Database to investigate if there is an association between a ≥90-day delay from TURBT in initiating CRT and overall survival (OS). We included patients with cT2-4N0M0 MIBC from 2004-2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped based on timing of CRT: ≤89 days after TURBT (‘earlier’) vs. ≥ 90 & <180 days after TURBT (‘delayed’). RESULTS: 1,387 (87.5%) received ‘earlier’ CRT (median 45 days post-TURBT, IQR: 34-59 days) and 197 (12.5%) received ‘delayed’ CRT (median 111 days post-TURBT, IQR: 98-130 days). Median OS was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for ‘earlier’ and ‘delayed’ CRT, respectively (p=0.94). On multivariable analysis, delayed CRT was not associated with an OS difference: hazard ratio, 1.05 (95% CI, 0.87-1.27); p=0.60. CONCLUSION: While these results are limited and require validation, short strategic treatment delays during a pandemic can be considered based on clinician judgement.


title: First evidence of a pro-inflammatory response to severe infection with influenza virus H1N1

text: The great majority of infections caused by the pandemic variant of the influenza virus (nvH1N1) are self-limited, but a small percentage of patients develop severe symptoms requiring hospitalization. Bermejo-Martin and colleagues have presented a pilot study describing the differences in the early immune response for patients both mildly and severely infected with nvH1N1. Patients who develop severe symptoms after nvH1N1 infection showed Th1 and Th17 'hypercytokinemia', compared to mildly infected patients and healthy controls. The mediators involved with the Th1 and Th17 profiles are known to be involved in antiviral, pro-inflammatory and autoimmune responses. This is the first work reporting the association of a pro-inflamatory immune response with a severe pandemic infection, although it is likely that more studies are needed to understand the detrimental or beneficial roles these cytokines play in the evolution of mild and severe nvH1N1 infection.


title: Synanthropic rodents as virus reservoirs and transmitters

text: This review focuses on reports of hepatitis E virus, hantavirus, rotavirus, coronavirus, and arenavirus in synanthropic rodents (Rattus rattus, Rattus norvegicus, and Mus musculus) within urban environments. Despite their potential impact on human health, relatively few studies have addressed the monitoring of these viruses in rodents. Comprehensive control and preventive activities should include actions such as the elimination or reduction of rat and mouse populations, sanitary education, reduction of shelters for the animals, and restriction of the access of rodents to residences, water, and food supplies.


Psoriasis, COVID‐19 and acute respiratory distress syndrome: focusing on the risk of concomitant biological treatment


docid: vmofcrim

title: Thromboprophylaxis in a patient with COVID‐19 and severe hemophilia A on emicizumab prophylaxis

text: COVID‐19 can be associated with coagulopathy (CAC, COVID‐19‐associated coagulopathy) with a high prothrombotic risk based on an intense inflammatory response to viral infection leading to immunothrombosis through different procoagulant pathways[1]. Emerging evidence suggests that the use of heparin in these patients could be associated with lower mortality[2].


title: COVID-19 suicides in Pakistan, dying off not COVID-19 fear but poverty? – The forthcoming economic challenges for a developing country

text: • Suicide increment during and afterwards a pandemic is highly common. • This study reports COVID-19 suicide cases in Pakistan for the first time. • Most of the suicides occur due to lockdown-related economic recession. • Fear of infection is the second suicide contributing factor. • Lockdown-related unemployment aggravates the life-threatening situation.


title: Gastrointestinal Pathology G.T. Williams Gastrointestinal Pathology

text: Unknown


Co-infections: potentially lethal and unexplored in COVID-19


title: Conflict and Emerging Infectious Diseases

text: Detection and control of emerging infectious diseases in conflict situations are major challenges due to multiple risk factors known to enhance emergence and transmission of infectious diseases. These include inadequate surveillance and response systems, destroyed infrastructure, collapsed health systems and disruption of disease control programs, and infection control practices even more inadequate than those in resource-poor settings, as well as ongoing insecurity and poor coordination among humanitarian agencies. This article outlines factors that potentiate emergence and transmission of infectious diseases in conflict situations and highlights several priority actions for their containment and control.


title: Comparison of Infectious Agents Susceptibility to Photocatalytic Effects of Nanosized Titanium and Zinc Oxides: A Practical Approach

text: Nanotechnology contributes towards a more effective eradication of pathogens that have emerged in hospitals, veterinary clinics, and food processing plants and that are resistant to traditional drugs or disinfectants. Since new methods of pathogens eradication must be invented and implemented, nanotechnology seems to have become the response to that acute need. A remarkable achievement in this field of science was the creation of self-disinfecting surfaces that base on advanced oxidation processes (AOPs). Thus, the phenomenon of photocatalysis was practically applied. Among the AOPs that have been most studied in respect of their ability to eradicate viruses, prions, bacteria, yeasts, and molds, there are the processes of TiO(2)/UV and ZnO/UV. Titanium dioxide (TiO(2)) and zinc oxide (ZnO) act as photocatalysts, after they have been powdered to nanoparticles. Ultraviolet (UV) radiation is an agent that determines their excitation. Methods using photocatalytic properties of nanosized TiO(2) and ZnO prove to be highly efficient in inactivation of infectious agents. Therefore, they are being applied on a growing scale. AOP-based disinfection is regarded as a very promising tool that might help overcome problems in food hygiene and public health protection. The susceptibility of infectious agents to photocatalylic processes can be generally arranged in the following order: viruses > prions > Gram-negative bacteria > Gram-positive bacteria > yeasts > molds.


title: Bronchoalveolar Interferon-α, Tumor Necrosis Factor-α, Interleukin-1, and Inflammation during Acute Influenza in Pigs: A Possible Model for Humans?

text: Biologically active interferon-α, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1) were detected in bronchoalveolar lavage (BAL) fluids of 3-week-old cesarian-derived colostrum-deprived pigs inoculated with H1N1 influenza virus. Cytokine titers and lung virus titers were significantly higher 18–24 h after inoculation than at 48–72 h after inoculation in all 4 litters of pigs examined. All three cytokines were positively correlated with a 3- to 4-fold increase in BAL cell numbers (P < .036) and with a drastic neutrophil infiltration (24%–77% of BAL cells vs. 0–1.5% in controls) (P < .001). In addition, cytokine production coincided with the onset of general and respiratory symptoms of influenza and with the development of a necrotizing bronchopneumonia. This study is the first demonstration of TNF-α and IL-1 in BAL fluids of a natural influenza virus host. It documents that pigs may be a highly valuable experimental model in human influenza virus pneumonia.


title: Use of recombinant feline interferon and glucocorticoid in the treatment of feline infectious peritonitis

text: Abstract A total of 12 clinically ill cats previously diagnosed as feline infectious peritonitis (FIP) were treated with a combination of recombinant feline interferon and glucocorticoid. A complete remission (over 2 years) and a partial remission (2 to 5 months) were observed in four (33.3%) and four (33.3%) cases, respectively. Those that survived for more than 2 years were all older cats (6 to 16 years old) with the effusive form of FIP.


title: Decline in PM2.5 Concentrations over Major Cities Around the World Associated with COVID-19

text: Abstract The COVID-19 started from Wuhan city in China, slowly spread across the globe after December 2019. Due to movement of people from one city to other cities, one country to other countries, infection spreads and COVID-19 became a pandemic. Efforts were made at local, regional and national levels to lockdown the movement of people and to keep infected one in quarantine or isolation to stop the spread of COVID-19. The traffic, market and small industries were closed, as a result pronounced decline in the concentrations of particulate matters (PM) were observed. Normally these sources contribute to the high concentrations of particulate matters (PM2.5) which represents air quality of a location. In this short communication, we present analysis of PM2.5 of major cities (New York, Los Angeles, Zaragoza, Rome, Dubai, Delhi, Mumbai, Beijing and Shanghai) around the world suffered severely with the COVID-19. Our analysis shows decline in PM2.5 concentration due to lockdown, mainly due to less movement of people to keep “social distancing” to control the spread of CORONA-19. The low concentrations of PM2.5 reflect the efforts made in the cities to curb the spread of infection, that improve air quality.


title: Deleted in colorectal cancer (netrin‐1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis

text: A 7‐year‐old neutered female domestic shorthaired cat born in Poland and then moved to Japan presented to the local clinic with recent onset of convulsive cluster seizures and status epilepticus. Magnetic resonance imaging revealed bilateral swelling of the hippocampus with T2 hyperintensity and contrast enhancing image, suggesting hippocampal necrosis. The cat completely recovered after treatment with antiepileptic drugs (AED) and administration of prednisolone (1 mg/kg PO q24h for 4 days and tapered). However, cluster seizures reoccurred and developed into status epilepticus despite increasing doses of AED. Although the convulsions were resolved by other AEDs, stupor and renal failure developed, and the cat was euthanized. Pathological findings were consistent with hippocampal necrosis. Immunological analysis for leucine‐rich glioma inactivated 1 (LGI1) autoantibodies was negative, but antibodies against DCC (deleted in colorectal carcinoma) known as netrin‐1 receptor were found. This report describes a case of feline autoimmune limbic encephalitis and hippocampal necrosis that were presumably associated with DCC autoantibodies.


docid: heislgtc

title: Long-lasting cough in an adult German population: incidence, symptoms, and related pathogens

text: Studies of the incidence of pertussis in adults have shown that it accounts for only 5–15% cases of prolonged coughing. We assessed the burden of suffering related to prolonged coughing and tried to identify further causative agents. Based on a sentinel study with 35 general practitioners in two German cities (Krefeld, Rostock), with 3,946 patients fulfilling the inclusion criteria, we estimated the incidence of prolonged coughing in adults. In 975 of these outpatients, PCR and/or serology for adenovirus, Bordetella pertussis and B. parapertussis, human metapneumovirus, influenza virus A and rhinovirus, parainfluenza virus, Mycoplasma pneumonia, and respiratory syncytial virus (RSV) were performed. Treatment data were extracted for a subgroup of 138 patients. Descriptive statistics, including Kaplan–Maier curves were generated. Yearly incidence ranged between 1.4 and 2.1% per population in the two cities. Adult patients sought medical attention only after a median of 3 weeks of coughing. Irrespective of smoking and unrelated to the identified pathogens, the median duration of coughing was 6 weeks, with an interquartile range of 4–11 weeks. In 48.3% of patients, possible pathogens were identified, among which adenovirus (15.1%), RSV (7.5%), B. pertussis (5.6%), and influenza viruses (4.0%) were most often found. Symptoms were not indicative of a specific agent and a total of 64% of patients received antibiotics. Prolonged adult coughing requiring medical attention prompts substantial healthcare use. Apart from B. pertussis, a broad range of pathogens was associated with the symptoms. However, patients sought medical attention too late to guide efficacious therapeutic interventions using the diagnostic tests.


title: Transient CFD simulation of the respiration process and inter-person exposure assessment

text: Abstract It is known that the person-to-person spreading of certain infectious diseases is related with the transmission of human exhaled air in the indoor environments, and this is suspected to be the case with the severe acute respiratory syndrome (SARS) outbreak. This paper presents the numerical analysis of the human respiration process and the transport of exhaled air by breathing, sneezing, and coughing and their potential impact on the adjacent person in a modeled room with displacement ventilation. In order to account for the influence of the thermal plume around the human body, a three-dimensional computational thermal manikin (CTM) with an accurate description of body geometry was applied. Some of the results were compared with those from former simulations and experiments. It was found that personal exposure to the exhaled air from the normal respiration process of other persons is very low in a modeled room with displacement ventilation. Personal exposure to pollution caused by sneezing or coughing is highly directional. When two occupants face each other the cross-infection may happen due to the long transport distance of the exhalation.


title: Evaluating the impact of international airline suspensions on the early global spread of COVID-19

text: Global airline networks play a key role in the global importation of emerging infectious diseases. Detailed information on air traffic between international airports has been demonstrated to be useful in retrospectively validating and prospectively predicting case emergence in other countries. In this paper, we use a well-established metric known as effective distance on the global air traffic data from IATA to quantify risk of emergence for different countries as a consequence of direct importation from China, and compare it against arrival times for the first 24 countries. Using this model trained on official first reports from WHO, we estimate time of arrival (ToA) for all other countries. We then incorporate data on airline suspensions to recompute the effective distance and assess the effect of such cancellations in delaying the estimated arrival time for all other countries. Finally we use the infectious disease vulnerability indices to explain some of the estimated reporting delays.


title: Viral RNA load and histological changes in tissues following experimental infection with an arterivirus of possums (wobbly possum disease virus)

text: Abstract Tissues from Australian brushtail possums (Trichosurus vulpecula) that had been experimentally infected with wobbly possum disease (WPD) virus (WPDV) were examined to elucidate pathogenesis of WPDV infection. Mononuclear inflammatory cell infiltrates were present in livers, kidneys, salivary glands and brains of WPD-affected possums. Specific staining was detected by immunohistochemistry within macrophages in the livers and kidneys, and undefined cell types in the brains. The highest viral RNA load was found in macrophage-rich tissues. The detection of viral RNA in the salivary gland, serum, kidney, bladder and urine is compatible with transmission via close physical contact during encounters such as fighting or grooming, or by contact with an environment that has been contaminated with saliva or urine. Levels of viral RNA remained high in all tissues tested throughout the study, suggesting that on-going virus replication and evasion of the immune responses may be important in the pathogenesis of disease.


title: Public Health Emergency of International Concern (PHEIC) has Declared Twice in 2014; Polio and Ebola at the Top

text: BACKGROUND: The current Ebola outbreak in West Africa and the large scale wild Polio virus outbreak in several countries are the top most issues among international public health and scientific communities' debates and concerns. These two outbreaks were judged to be declared as Public Health Emergency of International Concern (PHEIC) during 2014. This is the first time ever to have such circumstance of two PHEICs at the same time. DISCUSSION: PHEIC, which has to be declared by WHO Director General after a recommendation of IHR Emergency Committee; is observed to start in countries with fragile health system and conflict areas. Then it rapidly spread to threaten the global public health. The year 2014 has uniquely witnessed declaration of two events as PHEIC according to IHR (2005); Polio and Ebola Virus Disease (EVD). Both outbreaks are caused by viruses such as H1N1 which was previously declared as PHEIC in 2009. SUMMARY: Public Health Emergencies of International Concern in 2014 occurred in countries with weak health systems and conflicts and threatening the whole globe. International collaborative work is required to contain the event and to mobilize resources/capacities between countries. Moreover, public health surveillance systems as core capacity for IHR (2005) should be strengthened in all countries with focus on those with limited capacity and ongoing conflicts. The ultimate aim is timely detection of potential PHEIC events in the future along with early preparedness and response plans.


Colchicine and COVID‐19


title: Thoracic Surgeons’ Insights: Improving Thoracic Surgery Outcomes During the Coronavirus Disease 2019 Pandemic

text: [Figure: see text]


title: Inhalant Allergies in Children

text: Children with chronic or recurrent upper respiratory inflammatory disease (rhinitis) should be considered for inhalant allergies. Risk factors for inhalant allergies in children include a first-degree relative with allergies, food allergy in infancy, and atopic dermatitis. Although inhalant allergies are rare in infancy, inhalant allergies are common in older children and impair quality of life and productivity. Differentiating between viral and allergic rhinitis can be challenging in children, but the child's age, history, and risk factors can provide helpful information. Allergic rhinitis is a risk factor for asthma, and if one is present, medical consideration of the other is warranted.


title: Major Histocompatibility Complex Class I Haplotype Diversity in Chinese Rhesus Macaques

text: The use of Chinese-origin rhesus macaques (Macaca mulatta) for infectious disease immunity research is increasing despite the relative lack of major histocompatibility complex (MHC) class I immunogenetics information available for this population. We determined transcript-based MHC class I haplotypes for 385 Chinese rhesus macaques from five different experimental cohorts, providing a concise representation of the full complement of MHC class I major alleles expressed by each animal. In total, 123 Mamu-A and Mamu-B haplotypes were defined in the full Chinese rhesus macaque cohort. We then performed an analysis of haplotype frequencies across the experimental cohorts of Chinese rhesus macaques, as well as a comparison against a group of 96 Indian rhesus macaques. Notably, 35 of the 51 Mamu-A and Mamu-B haplotypes observed in Indian rhesus macaques were also detected in the Chinese population, with 85% of the 385 Chinese-origin rhesus macaques expressing at least one of these class I haplotypes. This unexpected conservation of Indian rhesus macaque MHC class I haplotypes in the Chinese rhesus macaque population suggests that immunologic insights originally gleaned from studies using Indian rhesus macaques may be more applicable to Chinese rhesus macaques than previously appreciated and may provide an opportunity for studies of CD8(+) T-cell responses between populations. It may also be possible to extend these studies across multiple species of macaques, as we found evidence of shared ancestral haplotypes between Chinese rhesus and Mauritian cynomolgus macaques.


title: COVID-19: Media coverage and financial markets behavior—A sectoral inquiry

text: We analyze the relationship between sentiment generated by coronavirus-related news with volatility of equity markets. The ongoing coronavirus outbreak (COVID-19) resulted in unprecedented news coverage and outpouring of opinions in this age of swift propagation of information. Ensuing uncertainty in financial markets leads to heightened volatility in prices. We find that overwhelming panic generated by the news outlets are associated with increasing volatility in the equity markets. Our results for individual economic sectors demonstrate that panic-laden news contributed to a greater extent to volatility in the sectors perceived to be most affected by coronavirus outbreak


title: Inhibition of Cavin3 Degradation by the Human Parainfluenza Virus Type 2 V Protein Is Important for Efficient Viral Growth

text: Cavin proteins have important roles in the formation of caveolae in lipid raft microdomains. Pulse-chase experiments of cells infected with human parainfluenza virus type 2 (hPIV-2) showed decreased proteasomal degradation of Cavin3. Overexpression of hPIV-2 V protein alone was sufficient to inhibit Cavin3 degradation. Immunoprecipitation analysis revealed that V protein bound to Cavin3. Trp residues within C-terminal region of V protein, as well as the N-terminal region of Cavin3, are important for V–Cavin3 interaction. Cavin3 knockdown suppressed hPIV-2 growth without affecting its entry, replication, transcription, or translation. Higher amounts of Cavin3 were observed in V protein-overexpressing cells than in control cells in lipid raft microdomains. Our data collectively suggest that hPIV-2 V protein binds to and stabilizes Cavin3, which in turn facilitates assembly and budding of hPIV-2 in lipid raft microdomains.


title: Fluorescence-Based Multiplex Protein Detection Using Optically Encoded Microbeads

text: Potential utilization of proteins for early detection and diagnosis of various diseases has drawn considerable interest in the development of protein-based multiplex detection techniques. Among the various techniques for high-throughput protein screening, optically-encoded beads combined with fluorescence-based target monitoring have great advantages over the planar array-based multiplexing assays. This review discusses recent developments of analytical methods of screening protein molecules on microbead-based platforms. These include various strategies such as barcoded microbeads, molecular beacon-based techniques, and surface-enhanced Raman scattering-based techniques. Their applications for label-free protein detection are also addressed. Especially, the optically-encoded beads such as multilayer fluorescence beads and SERS-encoded beads are successful for generating a large number of coding.


title: Chapter 12 Biology and Diseases of Dogs

text: Historically, the dog played an important role as a laboratory animal in biomedical research. Although numbers are declining, the use of dogs continues to be common in pharmacokinetics and cardiovascular studies. The normal biology of the dog as both a laboratory and a companion animal has been well studied and reference values are presented here as a clinical and experimental resource. This provides the necessary background to discuss the spontaneous diseases, including infectious and neoplastic conditions, prevalent in purpose bred as well as random source dogs used in biomedical research. In addition, diseases and conditions that arise secondary to the housing and experimental manipulation of dogs is discussed with emphasis on treatment and prevention.


Response to Letter Regarding “How Should the Rehabilitation Community Prepare for 2019-nCoV?”


Collaboration in the War against Viruses: A Multidisciplinary International Effort


title: Respiratory viruses in patients with influenza-like illness in Senegal: Focus on human respiratory adenoviruses

text: BACKGROUND: Human adenoviruses (HAdVs) are highly contagious pathogens that are associated with a wide spectrum of human illnesses involving the respiratory tract. In the present study, we investigate the epidemiologic and viral molecular features of HAdVs circulating in Senegal after 4 consecutive years of sentinel surveillance of influenza-like Illness cases. METHODOLOGY AND RESULTS: From January 2012 to December 2015 swabs were collected from consenting ILI outpatients. Adenoviral detection is performed by rRT-PCR with the Anyplex(™) II RV16 Detection kit (Seegene) and molecular characterization was performed using a partial hexon gene sequence. 6381 samples were collected. More than half of patients (51.7%; 3297/6381) were children of ≤ 5 years. 1967 (30.8%) were positive for HAdV with 1561 (79.4%) found in co-infection with at least one another respiratory virus. The most common co-detections were with influenza viruses (53.1%; 1045/1967), rhinoviruses (30%; 591/1967), enteroviruses (18.5%; 364/1967) and RSV (13.5%; 266/1967). Children under 5 were the most infected group (62.2%; 1224/1967; p <0.05). We noted that HAdV was detected throughout the year at a high level with detection peaks of different amplitudes without any clear seasonality. Phylogenetic analysis revealed species HAdV-C in majority, species HAdV-B and one HAdV- 4 genome type. The 9 HAdV-B species like strains from Senegal grouped with genome types HAdV-7, HAdV-55 and HAdV-11 as shown by a phylogenetic branch with a high bootstrap value of (88%). CONCLUSION: In conclusion, the results of the present study suggest strong year-round HAdV activity in Senegal, especially in children up to 5 years of age. Molecular studies revealed that the dominant species in circulation in patients with ILI appears to be HAdV-C and HAdV-B species. The circulation of though HAdV-7 and HAdV-55 genome types is of note as these serotypes are recognized causes of more severe and even fatal acute respiratory infections.


title: Early Experience Managing a High-volume Academic Orthopaedic Department During the Coronavirus Pandemic in New York City

text: Our orthopaedic surgery department at Montefiore Medical Center and Albert Einstein College of Medicine is located within the Bronx, a borough of New York City, and serves a densely populated urban community. Since the beginning of the novel coronavirus outbreak in New York City, the medical center was forced to rapidly adapt to the projected influx of critically ill patients. The aim of this report is to outline how our large academic orthopaedic surgery department adopted changes and alternative practices in response to the most daunting challenge to public health in our region in over a century. We hope that this report provides insight for others facing similar challenges.


title: Molecular signature of clinical severity in recovering patients with severe acute respiratory syndrome coronavirus (SARS-CoV)

text: BACKGROUND: Severe acute respiratory syndrome (SARS), a recent epidemic human disease, is caused by a novel coronavirus (SARS-CoV). First reported in Asia, SARS quickly spread worldwide through international travelling. As of July 2003, the World Health Organization reported a total of 8,437 people afflicted with SARS with a 9.6% mortality rate. Although immunopathological damages may account for the severity of respiratory distress, little is known about how the genome-wide gene expression of the host changes under the attack of SARS-CoV. RESULTS: Based on changes in gene expression of peripheral blood, we identified 52 signature genes that accurately discriminated acute SARS patients from non-SARS controls. While a general suppression of gene expression predominated in SARS-infected blood, several genes including those involved in innate immunity, such as defensins and eosinophil-derived neurotoxin, were upregulated. Instead of employing clustering methods, we ranked the severity of recovering SARS patients by generalized associate plots (GAP) according to the expression profiles of 52 signature genes. Through this method, we discovered a smooth transition pattern of severity from normal controls to acute SARS patients. The rank of SARS severity was significantly correlated with the recovery period (in days) and with the clinical pulmonary infection score. CONCLUSION: The use of the GAP approach has proved useful in analyzing the complexity and continuity of biological systems. The severity rank derived from the global expression profile of significantly regulated genes in patients may be useful for further elucidating the pathophysiology of their disease.


title: Characterization and evolution of porcine deltacoronavirus in the United States

text: Abstract Porcine deltacoronavirus (PDCoV) was identified in multiple states across the United States (US) in 2014. In this study, we investigate the presence of PDCoV in diagnostic samples, which were further categorized by case identification (ID), and the association between occurrence, age, specimen and location between March and September 2014. Approximately, 7% of the case IDs submitted from the US were positive for PDCoV. Specimens were categorized into eight groups, and the univariate analysis indicated that oral fluids had 1.89 times higher odds of detecting PDCoV compared to feces. While the 43–56 day age group had the highest percentage of PDCoV positives (8.4%), the univariate analysis indicated no significant differences between age groups. However, multivariable analysis for age adjusted by specimen indicated the >147 day age group had 59% lower odds than suckling pigs of being positive for PDCoV. The percentage of PDCoV in diagnostic samples decreased to <1% in September 2014. In addition, 19 complete PDCoV genomes were sequenced, and Bayesian analysis was conducted to estimate the emergence of the US clade. The evolutionary rate of the PDCoV genome is estimated to be 3.8×10−4 substitutions/site/year (2.3×10−4–5.4×10−4, 95% HPD). Our results indicate that oral fluids continue to be a valuable specimen to monitor swineherd health, and PDCoV has been circulating in the US prior to 2014.


title: Covid‐19: A Perspective on Africa's Capacity and Response

text: Global powerhouses with tried and tested health systems have struggled to contain the COVID‐19 pandemic. One is left to wonder what will be left of Africa, the second most populous continent after Asia, which is torn by civil wars, hunger, and diseases like AIDS and TB and, in recent years, the Ebola Virus Disease (EVD). The majority of countries’ health systems, already dependent on donor aid, are ill‐equipped and under‐resourced to deal with the raging pandemic. There is a lack of isolation and intensive care infrastructure, ventilators, and financial resources to bankroll the fight against COVID‐19 pandemic. However, there is some cause for optimism, for example, in West Africa where infrastructure like diagnostic testing facilities, intensive care units, surveillance, and systems for reporting emergencies used during the EVD outbreak of 2013‐2016 can be leveraged to fight the COVID‐19 pandemic. Further, a number of African countries have responded swiftly by activating the necessary political and financial tools to combat the pandemic. Technical support from continental bodies like the Africa Centres for Disease Control and global development partners has improved the capacity of the continent to handle the pandemic. In this article, the authors unpack, review, and share a perspective on Africa's capacity to contain and control the COVID‐19 pandemic and review the current response. This article is protected by copyright. All rights reserved.


title: Similar response rates and survival with PARP inhibitors for patients with solid tumors harboring somatic versus Germline BRCA mutations: a Meta-analysis and systematic review

text: BACKGROUND: PARP inhibitors (PARPi) have recently been approved for various malignancies based on the results of several clinical trials. However, these trials have mostly recruited patients with germline BRCA mutations, and it is unclear whether PARPi have similar efficacy in patients with somatic BRCA mutations. Our study aimed to determine the efficacy of PARPi in patients with somatic BRCA mutations. METHODS: We performed a meta-analysis comparing overall response rate to PARPi in patients harboring somatic versus germline BRCA mutations. We looked at studies including somatic and germline mutations in BRCA patients that received PARPi. RESULTS: After screening and removing duplicates, 18 studies met our criteria for including both somatic and germline BRCA mutations. Only 8 studies reported response rates for both somatic and germline BRCA mutations. In those studies, 24 out of 43 patients with somatic BRCA mutations (55.8%), and 69 out of 157 (43.9%) patients with germline BRCA patients had a response to therapy to PARPi. This difference was not statistically significant (p = 0.399). In all five studies that reported progression-free survival, there was no obvious difference in outcomes between somatic versus germline BRCA patients, however a precise statistical analysis could not be performed. CONCLUSION: Our meta-analysis and systematic review of the literature indicates similar response rates of PARPi therapy in patients with somatic and germline BRCA mutations. Investigation of use of PARPi therapy in a broader patient population, and the inclusion of somatic BRCA mutations in further clinical trials is paramount in improving therapeutic options for our patients.


title: Evaluation of the EUROIMMUN Anti-SARS-CoV-2 ELISA Assay for detection of IgA and IgG antibodies

text: As the Coronavirus 2019 (COVID-19) pandemic evolves, the development of immunoassays to help determine exposure and potentially predict immunity has become a pressing priority. In this report we present the performance of the EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples using recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Specimens from patients, with and without COVID-19 infection, were tested at the University of Chicago Clinical Microbiology and Immunology Laboratory. Of 86 samples from COVID-19 PCR-negative patients, including 28 samples positive for common human coronavirus strains, 76 tested negative and 10 tested positive for IgA (88.4% agreement, 95% CI: 79.9–93.6) while 84 tested negative and 2 tested positive for IgG (97.7% agreement, 95% CI: 91.9–99.6). Of 82 samples from COVID-19 PCR-positive patients, 14 tested negative and 68 tested positive for IgA (82.9% agreement, 95% CI: 73.4–89.5) while 27 tested negative and 55 tested positive for IgG (67.1% agreement, 95% CI: 56.3–76.3). Samples collected ≥4 days after positive PCR 38 of 42 (90.5% CI: 77.9–96.2) were positive for IgA, and 42 of 42 (100% 95% CI: 91.6–100) were positive for IgG, respectively. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay demonstrates good sensitivity for detection of IgA and excellent sensitivity for detection of IgG antibodies from samples collected ≥4 days, after COVID-19 diagnosis by PCR. This assay demonstrated only borderline cross reaction in 2 of the 28 samples from patients with common human coronaviruses infection, types NL63 and OC43.


title: Single B cell antibody technologies

text: Monoclonal antibodies (mAbs) are arguably the most significant class of biologics for use as pharmaceuticals and diagnostics. Many technological concepts exist for the generation and identification of therapeutically relevant mAbs, including the isolation and cloning of immunoglobulin (Ig) encoding genes from single B-lineage cells. This review summarizes various single B cell approaches and describes their use for the discovery of mAbs with potential therapeutic values or in basic research.


What is our threshold? Departmental planning for radiation oncology’s future in the time of COVID-19


title: Targeting Coronaviral Replication and Cellular JAK2 Mediated Dominant NF-κB Activation for Comprehensive and Ultimate Inhibition of Coronaviral Activity

text: Tylophorine-based compounds exert broad spectral, potent inhibition of coronaviruses. NF-κB activation is a common pro-inflammatory response of host cells to viral infection. The aims of this study were to (i) find an effective combination treatment for coronaviral infections through targeting of the virus per se and cellular NF-κB activity; and (ii) to study the underling mechanisms. We found that tylophorine-based compounds target the TGEV viral RNA and effectively inhibit TGEV replication. NF-κB inhibition also leads to anti-TGEV replication. NF-κB activation induced by TGEV infection was found to be associated with two convergent pathways, IKK-2_IκBα/p65 and JAK2 mediated p65 phosphorylation, in swine testicular cells. JAK2 inhibition either by CYT387 (a JAK family inhibitor) or by silencing JAK2-expression revealed a dominant JAK2 mediated p65 phosphorylation pathway for NF-κB activation and resulted in NF-κB inhibition, which overrode the IκBα regulation via the IKK-2. Finally, tylophorine-based compounds work cooperatively with CYT387 to impart comprehensive anti-TGEV activities. The combination treatment, wherein a tylophorine compound targets TGEV and a JAK2 inhibitor blocks the alternative dominant NF-κB activation mediated by JAK2, is more effective and comprehensive than either one alone and constitutes a feasible approach for the treatment of SARS-CoV or MERS-CoV.


title: Generation of a Nebulizable CDR-Modified MERS-CoV Neutralizing Human Antibody

text: Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe aggravating respiratory failure in infected patients, frequently resulting in mechanical ventilation. As limited therapeutic antibody is accumulated in lung tissue following systemic administration, inhalation is newly recognized as an alternative, possibly better, route of therapeutic antibody for pulmonary diseases. The nebulization process, however, generates diverse physiological stresses, and thus, the therapeutic antibody must be resistant to these stresses, remain stable, and form minimal aggregates. We first isolated a MERS-CoV neutralizing antibody that is reactive to the receptor-binding domain (RBD) of spike (S) glycoprotein. To increase stability, we introduced mutations into the complementarity-determining regions (CDRs) of the antibody. In the HCDRs (excluding HCDR3) in this clone, two hydrophobic residues were replaced with Glu, two residues were replaced with Asp, and four residues were replaced with positively charged amino acids. In LCDRs, only two Leu residues were replaced with Val. These modifications successfully generated a clone with significantly greater stability and equivalent reactivity and neutralizing activity following nebulization compared to the original clone. In summary, we generated a MERS-CoV neutralizing human antibody that is reactive to recombinant MERS-CoV S RBD protein for delivery via a pulmonary route by introducing stabilizing mutations into five CDRs.


title: Special Issue: MicroRNA Regulation in Health and Disease

text: Our understanding of non-coding RNA has significantly changed based on recent advances in genomics and molecular biology, and their role is recognized to include far more than a link between the sequence of DNA and synthesized proteins [...].


title: DNA Vaccine of SARS-Cov S Gene Induces Antibody Response in Mice

text: The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is one of the most important antigen candidates for vaccine design. In the present study, three fragments of the truncated S protein were expressed in E. coli, and analyzed with pooled sera of convalescence phase of SARS patients. The full length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The mouse serum IgG antibody against SARS-CoV was measured by ELISA with E. coli expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The results showed that all the three fragments of S protein expressed by E. coli was able to react with sera of SARS patients and the S gene DNA candidate vaccine could induce the production of specific IgG antibody against SARS-CoV efficiently in mice with seroconversion ratio of 75% after 3 times of immunization. These findings lay some foundations for further understanding the immunology of SARS-CoV and developing SARS vaccines.


Percutaneous Dilatational Tracheostomy in COVID-19 ECMO Patients: A Case Series


title: SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis of clinical features and pregnancy outcomes

text: BACKGROUND: Perform a systematic review and meta-analysis of SARS-CoV-2 infection and pregnancy. METHODS: Databases (Medline, Embase, Clinicaltrials.gov, Cochrane Library) were searched electronically on 6th April and updated regularly until 8th June 2020. Reports of pregnant women with reverse transcription PCR (RT-PCR) confirmed COVID-19 were included. Meta-analytical proportion summaries and meta-regression analyses for key clinical outcomes are provided. FINDINGS: 86 studies were included, 17 studies (2567 pregnancies) in the quantitative synthesis; other small case series and case reports were used to extract rarely-reported events and outcome. Most women (73.9%) were in the third trimester; 52.4% have delivered, half by caesarean section (48.3%). The proportion of Black, Asian or minority ethnic group membership (50.8%); obesity (38.2%), and chronic co-morbidities (32.5%) were high. The most commonly reported clinical symptoms were fever (63.3%), cough (71.4%) and dyspnoea (34.4%). The commonest laboratory abnormalities were raised CRP or procalcitonin (54.0%), lymphopenia (34.2%) and elevated transaminases (16.0%). Preterm birth before 37 weeks’ gestation was common (21.8%), usually medically-indicated (18.4%). Maternal intensive care unit admission was required in 7.0%, with intubation in 3.4%. Maternal mortality was uncommon (~1%). Maternal intensive care admission was higher in cohorts with higher rates of co-morbidities (beta=0.007, p<0.05) and maternal age over 35 years (beta=0.007, p<0.01). Maternal mortality was higher in cohorts with higher rates of antiviral drug use (beta=0.03, p<0.001), likely due to residual confounding. Neonatal nasopharyngeal swab RT-PCR was positive in 1.4%. INTERPRETATION: The risk of iatrogenic preterm birth and caesarean delivery was increased. The available evidence is reassuring, suggesting that maternal morbidity is similar to that of women of reproductive age. Vertical transmission of the virus probably occurs, albeit in a small proportion of cases. FUNDING: N/A


Perspective from Singapore and China on the Covid-19 pandemic: the new world order for ophthalmic practice


docid: nmmkkvaq

title: Phylogenetic and gene-centric metagenomics of the canine intestinal microbiome reveals similarities with humans and mice

text: This study is the first to use a metagenomics approach to characterize the phylogeny and functional capacity of the canine gastrointestinal microbiome. Six healthy adult dogs were used in a crossover design and fed a low-fiber control diet (K9C) or one containing 7.5% beet pulp (K9BP). Pooled fecal DNA samples from each treatment were subjected to 454 pyrosequencing, generating 503 280 (K9C) and 505 061 (K9BP) sequences. Dominant bacterial phyla included the Bacteroidetes/Chlorobi group and Firmicutes, both of which comprised ∼35% of all sequences, followed by Proteobacteria (13–15%) and Fusobacteria (7–8%). K9C had a greater percentage of Bacteroidetes, Fusobacteria and Proteobacteria, whereas K9BP had greater proportions of the Bacteroidetes/Chlorobi group and Firmicutes. Archaea were not altered by diet and represented ∼1% of all sequences. All archaea were members of Crenarchaeota and Euryarchaeota, with methanogens being the most abundant and diverse. Three fungi phylotypes were present in K9C, but none in K9BP. Less than 0.4% of sequences were of viral origin, with >99% of them associated with bacteriophages. Primary functional categories were not significantly affected by diet and were associated with carbohydrates; protein metabolism; DNA metabolism; cofactors, vitamins, prosthetic groups and pigments; amino acids and derivatives; cell wall and capsule; and virulence. Hierarchical clustering of several gastrointestinal metagenomes demonstrated phylogenetic and metabolic similarity between dogs, humans and mice. More research is required to provide deeper coverage of the canine microbiome, evaluate effects of age, genetics or environment on its composition and activity, and identify its role in gastrointestinal disease.