title: The Okinawa Infectious Diseases Initiative

text: At the Kyushu–Okinawa Group of Eight summit in 2000, Japan announced the Okinawa Infectious Diseases Initiative (IDI) and pledged to spend US$3 billion over a five year period to combat infectious and parasitic diseases in developing countries. The IDI has exceeded expectations, spending more than US$4 billion over four years. The IDI is a unique initiative with its own philosophical basis and specifically tailored interventions and measures that helped to initiate worldwide political and financial commitments in the fight against infectious diseases. Notably, it promoted partnerships among stakeholders and emphasized comprehensive and inter-sectoral approaches (i.e. coordination and collaboration between health and other sectors). It helped to create a new vision of what is possible in the global effort against communicable diseases and has been instrumental in shaping the changing environments of development assistance, poverty reduction and other trends to reduce the impact of infectious and parasitic diseases.


title: The Effect of Recycled Water Information Disclosure on Public Acceptance of Recycled Water—Evidence from residents of Xi'an, China

text: Recycled water, the secondary water source of a city, is vital to alleviate regional water resource shortage and promote environmental conservation. The attitude and acceptance toward recycled water of the public, its direct user, hold the key to the implementation of a recycled water project. Currently, the public’s low intention of using recycled water constitutes the biggest obstacle to its popularization. To identify the factors of public acceptance of recycled water and their influence path, this study analyzes the effect mechanism of information disclosure of recycled water on the public’s acceptance of it based on the consciousness-context-behavior theory and by adopting a structural equation model. The results are as follows: (1) The public’s consciousness of water saving, risk perception of recycled water, and consciousness of environmental responsibility can effectively promote public acceptance of recycled water; (2) The consciousness of water saving and that of environmental responsibility have a significant effect on public acceptance of recycled water, and so do the consciousness of water saving and the risk perception of recycled water; and (3) Recycled water information disclosure has the most significant regulatory effect on consciousness and public acceptance.


title: Successful resolution of dermatophyte mycetoma following terbinafine treatment in two cats

text: Microsporum canis sensitive to itraconazole and terbinafine was isolated from two cats presented with generalized dermatophytosis and dermatophyte mycetoma. Itraconazole therapy was withdrawn through lack of efficacy in one cat (a Persian) and unacceptable adverse effects in the other (a Maine Coon). Both cats achieved clinical and mycological cure after 12–14 weeks therapy with 26–31 mg kg(−1) terbinafine every 24 h per os (PO). Clinical signs in the Maine Coon resolved completely after 7 weeks treatment. Four weeks of therapy with additional weekly washes with a 2% chlorhexidine/2% miconazole shampoo following clipping produced a 98% reduction in the Persian cat's mycetoma, which was then surgically excised. Recurrent generalized dermatophytosis in the Persian cat has been managed with pulse therapy with 26 mg kg(−1) terbinafine every 24 h PO for 1 week in every month. No underlying conditions predisposing to dermatophytosis were found in either cat despite extensive investigation. Terbinafine administration was associated with mild to moderate lethargy in the Persian cat, but no other adverse effects or changes in blood parameters were seen. To the best of the authors’ knowledge this is the first report of a dermatophyte mycetoma in a Maine Coon and of successful resolution of this condition in cats following terbinafine therapy.


docid: afcgqjwq

title: Precision epidemiology for infectious disease control

text: Advances in genomics and computing are transforming the capacity for the characterization of biological systems, and researchers are now poised for a precision-focused transformation in the way they prepare for, and respond to, infectious diseases. This includes the use of genome-based approaches to inform molecular diagnosis and individual-level treatment regimens. In addition, advances in the speed and granularity of pathogen genome generation have improved the capability to track and understand pathogen transmission, leading to potential improvements in the design and implementation of population-level public health interventions. In this Perspective, we outline several trends that are driving the development of precision epidemiology of infectious disease and their implications for scientists’ ability to respond to outbreaks.


title: Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

text: Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.


Characteristics of health worker fatality in China during the outbreak of COVID-19 infection


title: Acute Stroke Care in a New York City Comprehensive Stroke Center during the COVID-19 Pandemic

text: BACKGROUND AND PURPOSE: The coronavirus disease-2019 (COVID-19) pandemic caused unprecedented demand and burden on emergency health care services in New York City. We aim to describe our experience providing acute stroke care at a comprehensive stroke center (CSC) and the impact of the pandemic on the quality of care for patients presenting with acute ischemic stroke (AIS). METHODS: We retrospectively analyzed data from a quality improvement registry of consecutive AIS patients at New York University Langone Health's CSC between 06/01/2019-05/15/2020. During the early stages of the pandemic, the acute stroke process was modified to incorporate COVID-19 screening, testing, and other precautionary measures. We compared stroke quality metrics including treatment times and discharge outcomes of AIS patients during the pandemic (03/012020-05/152020) compared with a historical pre-pandemic group (6/1/2019-2/29/2020). RESULTS: A total of 754 patients (pandemic-120; pre-pandemic-634) were admitted with a principal diagnosis of AIS; 198 (26.3%) received alteplase and/or mechanical thrombectomy. Despite longer median door to head CT times (16 vs 12 minutes; p=0.05) and a trend towards longer door to groin puncture times (79.5 vs. 71 minutes, p=0.06), the time to alteplase administration (36 vs 35 minutes; p=0.83), door to reperfusion times (103 vs 97 minutes, p=0.18) and defect-free care (95.2% vs 94.7%; p=0.84) were similar in the pandemic and pre-pandemic groups. Successful recanalization rates (TICI≥2b) were also similar (82.6% vs. 86.7%, p=0.48). After adjusting for stroke severity, age and a prior history of transient ischemic attack/stroke, pandemic patients had increased discharge mortality (adjusted OR 2.90 95% CI 1.77 – 7.17, p = 0.021) CONCLUSION: Despite unprecedented demands on emergency healthcare services, early multidisciplinary efforts to adapt the acute stroke treatment process resulted in keeping the stroke quality time metrics close to pre-pandemic levels. Future studies will be needed with a larger cohort comparing discharge and long-term outcomes between pre-pandemic and pandemic AIS patients.


title: Broad-spectrum antiviral activity of carbodine, the carbocyclic analogue of cytidine

text: Abstract Carbocyclic cytidine (C-Cyd) is a broad-spectrum antiviral agent active against DNA viruses [pox (vaccinia)], (+)RNA viruses [toga (Sindbis, Semliki forest), corona], (−)RNA viruses [orthomyxo (influenza), paramyxo (parainfluenza, measles), rhabdo (vesicular stomatitis)] and (±)RNA viruses (reo). The target enzyme of C-Cyd is supposed to be CTP synthetase that converts UTP to CTP. In keeping with this assumption are the observations that (i) C-Cyd effects a dose-dependent inhibition of RNA synthesis in both virus-infected and uninfected cells, and (ii) exogenous addition of either Urd or Cyd reverses both the antiviral and cytocidal activity of C-Cyd, whereas addition of dThd or dCyd fails to do so. The selectivity of C-Cyd against Sindbis, vesicular stomatitis and reo virus is markedly increased when C-Cyd is combined with Cyd (10 μg/mL). This combination may therefore be worth pursuing as a chemotherapeutic modality for the treatment of virus infections.


title: Exploring IRES Region Accessibility by Interference of Foot-and-Mouth Disease Virus Infectivity

text: Translation initiation of picornavirus RNA is driven by an internal ribosome entry site (IRES) element located upstream of the initiator codon. RNA structure organization as well as RNA-protein interaction plays a fundamental role in internal initiation. IRES activity has been mainly analyzed in the context of reporter genes, lacking regions of the viral genome potentially affecting translation efficiency. With the aim to understand the vulnerability of the IRES and translation start region to small molecules in the context of the viral genome, we designed a set of customized RNase-resistant 2′O-methyl antisense oligoribonucleotides (2′OMe AONs) based on RNA structure data. These AONs were then used to monitor their capacity to interfere viral RNA translation, and thus, to inhibit virus yield. Foot-and-mouth disease virus (FMDV) RNA translation can be initiated at two in-frame AUG codons. We show here that a 2′OMe AON complementary to AUG2 inhibited viral multiplication more efficiently than the one that targeted AUG1. Furthermore, the response of the viral RNA to AONs targeting the IRES region denoted important differences between tissue culture cells and cell-free systems, reinforcing the need to analyze viral RNA response in living cells. Importantly, we have identified four specific motifs within the IRES element that are targets for viral inhibitors both in tissue culture cells and in cell-free systems. The identified targets define accessible regions to small molecules, which disturb either the RNA structural organization or the RNA-protein interactions needed to initiate translation in FMDV RNA.


INFECTIONS, INFLAMMATORY MARKERS AND SCHIZOPHRENIA


title: Collaborative Intervention of Middle East Respiratory Syndrome: Rapid Response Team

text: On May 20th 2015, a 68 year old man was the first to be diagnosed with Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) in Korea. He travelled to Bahrain, Saudi Arabia, and Qatar for 16 days. On May 4th 2015, the patient entered Korea, with febrile sense and respiratory symptoms that appeared on May 11th. The MERS-CoV Outbreak became worse and several patients had to be admitted throughout various hospitals starting at the beginning of June. This situation led to a nationwide chaos. The Rapid Response Team (RRT) was organized after the Korean government's calling for specialists that were composed of 15 Infectious disease Doctors and 2 Infection Control professionals on the 8th of June 2015. The main purpose of the RRT were: 1) consultation to the Government controlling MERS-CoV outbreak. 2) Visit hospitals that were exposed to MERS-CoV infected patients, and to provide advice regarding infection control strategy for rehabilitating of the exposed hospitals. Since June 8th, the RRT visited more than 10 hospitals and an effective consultation was carried out. Most of the hospitals were recovering from the MERS outbreak since early July. Cooperation between the government and private sector experts was very effective. The efforts of government and private sector experts overcame the initial chaos situation. It could prevent further deterioration of the MERS outbreak.


docid: odbbgven

title: Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms

text: OBJECTIVE: To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population. METHODS: The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay. RESULTS: The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients. CONCLUSION: Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.


title: Decreased expression of eukaryotic initiation factor 3f is an adverse prognostic factor for stage I–III gastric cancer

text: BACKGROUND: It has been demonstrated that eIF3f expression is significantly decreased in many human cancers, a fact which plays an important role in human cancer. However, the expression of eIF3f in gastric cancer (GC) is not well understood to date. Therefore, the aim of this study is to detect the expression of eIF3f in GC. METHODS: The expression of eIF3f was examined by immunohistochemistry in tissues with stage I to III GC and adjacent non-cancerous tissues (ANCT) of 195 gastrectomy specimens; clinicopathological results, including survival, were analyzed. RESULTS: The positive expression rate of eIF3f was significantly higher in ANCT tissues than in GC. eIF3f levels were correlated with more advanced tumor stages and likelihood of recurrence (all P <0.05). The Kaplan-Meier survival curves indicated that decreased expression of eIF3f could serve as a prognosis marker for poor outcome of GC patients (P = 0.04). CONCLUSIONS: eIF3f may play an important role in recurrence, thus representing a promising predictive marker for the prognosis of GC.


N-acetylcysteine as a potential treatment for novel coronavirus disease 2019


title: Ribosomal stress and Tp53-mediated neuronal apoptosis in response to capsid protein of the Zika virus

text: We report here that in rat and human neuroprogenitor cells as well as rat embryonic cortical neurons Zika virus (ZIKV) infection leads to ribosomal stress that is characterized by structural disruption of the nucleolus. The anti-nucleolar effects were most pronounced in postmitotic neurons. Moreover, in the latter system, nucleolar presence of ZIKV capsid protein (ZIKV-C) was associated with ribosomal stress and apoptosis. Deletion of 22 C-terminal residues of ZIKV-C prevented nucleolar localization, ribosomal stress and apoptosis. Consistent with a casual relationship between ZIKV-C-induced ribosomal stress and apoptosis, ZIKV-C-overexpressing neurons were protected by loss-of-function manipulations targeting the ribosomal stress effector Tp53 or knockdown of the ribosomal stress mediator RPL11. Finally, capsid protein of Dengue virus, but not West Nile virus, induced ribosomal stress and apoptosis. Thus, anti-nucleolar and pro-apoptotic effects of protein C are flavivirus-species specific. In the case of ZIKV, capsid protein-mediated ribosomal stress may contribute to neuronal death, neurodevelopmental disruption and microcephaly.


title: Engineering Coronaviruses to Evaluate Emergence and Pathogenic Potential

text: A recent study provides a platform for generating infectious coronavirus genomes using sequence data, examining their capabilities of replicating in human cells and causing diseases in animal models, and evaluating therapeutics and vaccines. Similar approaches could be used to assess the potential of human emergence and pathogenicity for other viruses.


title: MERS and the dromedary camel trade between Africa and the Middle East

text: Dromedary camels are the most likely source for the coronavirus that sporadically causes Middle East respiratory syndrome (MERS) in humans. Serological results from archived camel sera provide evidence for circulation of MERS coronavirus (MERS-CoV) among dromedary camels in the Greater Horn of Africa as far back as 1983 and in Saudi Arabia as far back as 1992. High seroprevalences of MERS-CoV antibodies and the high virus prevalence in Saudi Arabian dromedary camels indicate an endemicity of the virus in the Arabian Peninsula, which predates the 2012 human MERS index case. Saudi Arabian dromedary camels show significantly higher MERS-CoV carrier rates than dromedary camels imported from Africa. Two MERS-CoV lineages identified in Nigerian camels were found to be genetically distinct from those found in camels and humans in the Middle East. This supports the hypothesis that camel imports from Africa are not of significance for circulation of the virus in camel populations of the Arabian Peninsula.


title: In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets

text: Abstract It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8+ cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8+ cells in 2-week-old infected piglets (33.4±12.6%) was followed by a decline to 7.3±3.0 and 11.1±3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6±0.9, 2.3±1.8 and 1.9±0.5% CD8+ cells, only. In peripheral blood, however, the average number of CD8+ cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8±1.9, 2.9±1.8 and 3.2±1.7×106 CD8+ cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8+ cells were 0.9±0.2, 1.9±1.7 and 1.6±0.5×106/ml, respectively. Furthermore, the numbers of CD2+, CD4+CD8+ and SLA-classII+ cells, respectively, in peripheral blood, together with the levels of CD2+ and CD3+ cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8+ cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.


title: Structural basis for catalysis and substrate specificity of a 3C-like cysteine protease from a mosquito mesonivirus

text: Abstract Cavally virus (CavV) is a mosquito-borne plus-strand RNA virus in the family Mesoniviridae (order Nidovirales). We present X-ray structures for the CavV 3C-like protease (3CLpro), as a free enzyme and in complex with a peptide aldehyde inhibitor mimicking the P4-to-P1 residues of a natural substrate. The 3CLpro structure (refined to 1.94 Å) shows that the protein forms dimers. The monomers are comprised of N-terminal domains I and II, which adopt a chymotrypsin-like fold, and a C-terminal α-helical domain III. The catalytic Cys-His dyad is assisted by a complex network of interactions involving a water molecule that mediates polar contacts between the catalytic His and a conserved Asp located in the domain II-III junction and is suitably positioned to stabilize the developing positive charge of the catalytic His in the transition state during catalysis. The study also reveals the structural basis for the distinct P2 Asn-specific substrate-binding pocket of mesonivirus 3CLpros.


title: Quantitative phosphoproteome on the silkworm (Bombyx mori) cells infected with baculovirus

text: BACKGROUND: Bombyx mori has become an important model organism for many fundamental studies. Bombyx mori nucleopolyhedrovirus (BmNPV) is a significant pathogen to Bombyx mori, yet also an efficient vector for recombinant protein production. A previous study indicated that acetylation plays many vital roles in several cellular processes of Bombyx mori while global phosphorylation pattern upon BmNPV infection remains elusive. METHOD: Employing tandem mass tag (TMT) labeling and phosphorylation affinity enrichment followed by high-resolution LC-MS/MS analysis and intensive bioinformatics analysis, the quantitative phosphoproteome in Bombyx mori cells infected by BmNPV at 24 hpi with an MOI of 10 was extensively examined. RESULTS: Totally, 6480 phosphorylation sites in 2112 protein groups were identified, among which 4764 sites in 1717 proteins were quantified. Among the quantified proteins, 81 up-regulated and 25 down-regulated sites were identified with significant criteria (the quantitative ratio above 1.3 was considered as up-regulation and below 0.77 was considered as down-regulation) and with significant p-value (p < 0.05). Some proteins of BmNPV were also hyperphosphorylated during infection, such as P6.9, 39 K, LEF-6, Ac58-like protein, Ac82-like protein and BRO-D. CONCLUSION: The phosphorylated proteins were primary involved in several specific functions, out of which, we focused on the binding activity, protein synthesis, viral replication and apoptosis through kinase activity.


title: Three 3D graphical representations of DNA primary sequences based on the classifications of DNA bases and their applications

text: Abstract In this article, we introduce three 3D graphical representations of DNA primary sequences, which we call RY-curve, MK-curve and SW-curve, based on three classifications of the DNA bases. The advantages of our representations are that (i) these 3D curves are strictly non-degenerate and there is no loss of information when transferring a DNA sequence to its mathematical representation and (ii) the coordinates of every node on these 3D curves have clear biological implication. Two applications of these 3D curves are presented: (a) a simple formula is derived to calculate the content of the four bases (A, G, C and T) from the coordinates of nodes on the curves; and (b) a 12-component characteristic vector is constructed to compare similarity among DNA sequences from different species based on the geometrical centers of the 3D curves. As examples, we examine similarity among the coding sequences of the first exon of beta-globin gene from eleven species and validate similarity of cDNA sequences of beta-globin gene from eight species.


Enfermedad COVID-19: el hospital del futuro ya está aquí


title: Molecular and Cellular Mechanisms for PRRSV Pathogenesis and Host Response to Infection

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) has caused tremendous amounts of economic losses to the swine industry for more than three decades, but its control is still unsatisfactory. A significant amount of information is available for host cell-virus interactions during infection, and it is evident that PRRSV has evolved to equip various strategies to disrupt the host antiviral system and provide favorable conditions for survival. The current study reviews viral strategies for modulations of cellular processes including innate immunity, apoptosis, microRNAs, inflammatory cytokines, and other cellular pathways.


title: Kinedoc, CISMeF et COVID-19: la nécessité de référencer les brochures pédagogiques pour le patient

text: Résumé La crise inédite du Covid-19 a fait apparaitre le besoin de recenser et de diffuser des supports didactiques thérapeutiques à destination des patients (auto-rééducation) en complément des séances, notamment dans le cadre du télésoin. Kinedoc, la banque documentaire francophone, a collaboré avec le D2IM du CHU de Rouen pour créer ce nouveau type de documents en adaptant le moteur de recherche du CISMeF qui recense déjà des publications similaires dans d’autres domaines. Désormais, il sera possible de trouver et de télécharger dans Kinedoc des brochures thérapeutiques dont le Collège de la Masso-Kinésithérapie (CMK) aura préalablement validé la conformité. Chaque société savante, association ou kinésithérapeute/physiothérapeute peut proposer de partager ses « brochures pédagogiques pour le patient », en les envoyant par courriel à cette adresse : secretariat@college-mk.org. Abstract With this unprecedented Covid-19 crisis, appeared the need to draw up a list and to spread pedagogical and therapeutic media for patients (self-rehabilitation), in addition to sessions, particularly in "telehealth". Kinedoc, a French database, collaborated with the D2IM of Rouen’s university hospital to create this new type of documents, adjusting CISMeF’s search engine, which has already listed similar publications in other fields. From now on, it will be possible to find and download in Kinedoc therapeutic brochures certified by the "Collège de la Masso-Kinésithérapie" (CMK). Every academic society, association or physiotherapist can suggest sharing its "pedagogical brochures for patients" by sending them to this address: secretariat@college-mk.org.


title: Redesigning a PhD measurement course for a new era in nursing science

text: Abstract Measurement is at the core of the research process. At the PhD level, students need to develop an in-depth understanding of measures relevant to their area of work and refine their knowledge of measurement issues. Traditionally, measurement coursework in Nursing focused on the psychometric evaluation of instruments measuring cognition and behavior. However, in the age of Big Data, precision medicine, and translational science, PhD students need to develop knowledge and skills relevant to these fields and to collaborate with experts from the different disciplines. Therefore, Nursing faculty need to recognize the state-of-the-science of nursing research and tend to a variety of measurement issues across a spectrum of operationalized concepts. Herein we present an overview of learning outcomes, instructional content and methods of delivery for a contemporary PhD-level course on measurement for Nursing Science. We also present our experience in the design, implementation, and evaluation of a novel PhD measurement course.


title: The role of the hotel industry in the response to emerging epidemics: a case study of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong

text: BACKGROUND: The global travel and tourism industry has been rapidly expanding in the past decades. The traditional focus on border screening, and by airline and cruise industries may be inadequate due to the incubation period of an infectious disease. This case study highlights the potential role of the hotel industry in epidemic preparedness and response. METHODS: This case study focuses on the epidemic outbreaks of SARS in 2003 and H1N1 swine flu in 2009 in Hong Kong, and the subsequent guidelines published by the health authority in relation to the hotel industry in Hong Kong which provide the backbone for discussion. RESULTS: The Metropole Hotel hastened the international spread of the 2003 SARS outbreak by the index case infecting visitors from Singapore, Vietnam, Canada as well as local people via close contact with the index case and the environmental contamination. The one-week quarantine of more than 300 guests and staff at the Metropark Hotel during the 2009 H1N1 swine flu exposed gaps in the partnership with the hotel industry. The subsequent guidelines for the hotel industry from the Centre of Health Protection focused largely on the maintenance of hygiene within the hotel premises. CONCLUSION: Positive collaborations may bring about effective preparedness across the health and the tourism sectors for future epidemics. Regular hygiene surveillance at hotel facilities, and developing coordination mechanism for impending epidemics on the use of screening, swift reporting and isolation of infected persons may help mitigate the impact of future events. Preparedness and contingency plans for infectious disease control for the hotel industry requires continuous engagement and dialogue.


title: Tropism and replication of Middle East respiratory syndrome coronavirus from dromedary camels in the human respiratory tract: an in-vitro and ex-vivo study

text: Summary Background Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic infection causing severe viral pneumonia, with index cases having resided in or recently travelled to the Arabian peninsula, and is a global concern for public health. Limited human-to-human transmission, leading to some case clusters, has been reported. MERS-CoV has been reported in dromedary camels but phenotypic characterisation of such viruses is limited. We aimed to compare MERS-CoV isolates from dromedaries in Saudi Arabia and Egypt with a prototype human MERS-CoV to assess virus replication competence and cell tropism in ex-vivo cultures of human bronchus and lung. Methods We characterised MERS-CoV viruses from dromedaries in Saudi Arabia and Egypt and compared them with a human MERS-CoV reference strain. We assessed viral replication kinetics and competence in Vero-E6 cells (rhesus monkey), tissue tropism in cultures of ex-vivo human bronchial and lung tissues, and cytokine and chemokine induction, gene expression, and quantification of viral RNA in Calu-3 cells (human respiratory tract). We used mock-infected tissue as negative controls for ex-vivo experiments and influenza A H5N1 as a positive control for cytokine and chemokine induction experiments in Calu-3 cells. Findings We isolated three dromedary strains, two from Saudi Arabia (Dromedary/Al-Hasa-KFU-HKU13/2013 [AH13] and Dromedary/Al-Hasa-KFU-HKU19D/2013 [AH19D]), and one from Egypt (Dromedary/Egypt-NRCE-HKU270/2013 [NRCE-HKU270]). The human and dromedary MERS-CoV strains had similar viral replication competence in Vero-E6 cells and respiratory tropism in ex-vivo cultures of the human respiratory tract, and had similar ability to evade interferon responses in the human-respiratory-tract-derived cell line Calu-3. Interpretation The similarity of virus tropism and replication competence of human and dromedary MERS-CoV from the Arabian peninsula, and genetically diverse dromedary viruses from Egypt, in ex-vivo cultures of the human respiratory tract suggests that dromedary viruses from Saudi Arabia and Egypt are probably infectious to human beings. Exposure to zoonotic MERS-CoV is probably occurring in a wider geographical region beyond the Arabian peninsula. Funding King Faisal University, Egyptian National Research Centre, Hong Kong Food and Health Bureau, National Institute of Allergy and Infectious Diseases, and European Community Seventh Framework Program.


title: Challenges presented by MERS corona virus, and SARS corona virus to global health

text: Numerous viral infections have arisen and affected global healthcare facilities. Millions of people are at severe risk of acquiring several evolving viral infections through several factors. In the present article we have described about risk factors, chance of infection, and prevention methods of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV), human coronaviruses (CoVs) frequently cause a normal cold which is mild and self-restricting. Zoonotic transmission of CoVs such as the newly discovered MERS-CoV and SARS-CoV, may be associated with severe lower respiratory tract infection. The present review provides the recent clinical and pathological information on MERS and SARS. The task is to transform these discoveries about MERS and SARS pathogenesis and to develop intervention methods that will eventually allow the effective control of these recently arising severe viral infections. Global health sector has learnt many lessons through the recent outbreak of MERS and SARS, but the need for identifying new antiviral treatment was not learned. In the present article we have reviewed the literature on the several facets like transmission, precautions and effectiveness of treatments used in patients with MERS-CoV and SARS infections.


title: COVID-19 and diabetes mellitus: An unholy interaction of two pandemics

text: Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “diabetes mellitus”, “SARS”, “infection” and “management of diabetes mellitus” with interposition of the Boolean operator “AND”. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.


title: The Functional Protein Microarray as Molecular Decathlete: A Versatile Player in Clinical Proteomics

text: Functional protein microarrays were developed as a high-throughput tool to overcome the limitations of DNA microarrays and to provide a versatile platform for protein functional analyses. Recent years have witnessed tremendous growth in the use of protein microarrays, particularly functional protein microarrays, to address important questions in the field of clinical proteomics. In this review, we will summarize some of the most innovative and exciting recent applications of protein microarrays in clinical proteomics, including biomarker identification, pathogen-host interactions, and cancer biology.


title: MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2

text: Middle East respiratory syndrome coronavirus (MERS-CoV) causes sporadic zoonotic disease and healthcare-associated outbreaks in human. MERS is often complicated by acute respiratory distress syndrome (ARDS) and multi-organ failure(1,2). The high incidence of renal failure in MERS is a unique clinical feature not often found in other human coronavirus infections(3,4). Whether MERS-CoV infects the kidney and how it triggers renal failure are not understood(5,6). Here, we demonstrated renal infection and apoptotic induction by MERS-CoV in human ex vivo organ culture and a nonhuman primate model. High-throughput analysis revealed that the cellular genes most significantly perturbed by MERS-CoV have previously been implicated in renal diseases. Furthermore, MERS-CoV induced apoptosis through upregulation of Smad7 and fibroblast growth factor 2 (FGF2) expression in both kidney and lung cells. Conversely, knockdown of Smad7 effectively inhibited MERS-CoV replication and protected cells from virus-induced cytopathic effects. We further demonstrated that hyperexpression of Smad7 or FGF2 induced a strong apoptotic response in kidney cells. Common marmosets infected by MERS-CoV developed ARDS and disseminated infection in kidneys and other organs. Smad7 and FGF2 expression were elevated in the lungs and kidneys of the infected animals. Our results provide insights into the pathogenesis of MERS-CoV and host targets for treatment. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nmicrobiol.2016.4) contains supplementary material, which is available to authorized users.


title: Viral transport and the cytoskeleton

text: Abstract In the past decade, studies into the way in which intracellular bacterial pathogens hijack and subvert their hosts have provided many important insights into regulation of the actin cytoskeleton and cell motility, in addition to increasing our understanding of the infection process. Viral pathogens, however, may ultimately unlock more cellular secrets as they are even more dependent on their hosts during their life cycle.


title: Decrease in acute coronary syndrome presentations during the COVID19 pandemic in upstate New York

text: Abstract Introduction The COVID 19 virus is a devastating pandemic that has impacted the US healthcare system significantly. More than one study reported a significant decrease in acute coronary syndrome admissions during that pandemic which is still due to unknown reasons. Methods This is a retrospective non-controlled multi-centered study of 180 patients (117 males and 63 females) with acute coronary syndrome (STEMI and NSTEMI) admitted during March/April of 2019 and March/April 2020 in Upstate New York. Results A total of 113 patients (61.9% males, 38.1% females) with a mean age of 72.3±14.2 presented during March/April 2019 with ACS (STEMI + NSTEMI) while only 67 (70.1% males, 29.9% females) COVID 19 negative patients with a mean age of 65.1±14.5 presented during the same period (March/April) in 2020. This is a drop by 40.7% (P <.05) of total ACS cases during the COVID 19 pandemic. In NSTEMI patients, 36.4% presented late (>24hours of symptoms) during the COVID 19 pandemic in comparison with 2019 (27.1%, P =.033). Conclusion The COVID 19 pandemic led to a substantial drop by 40.7% (P <.05) of total ACS admissions in our area. This decrease in hospital admissions and late presentations can be a worrisome sign for an increase in future complications of myocardial infarctions.


title: The Fertility Quality of Life (FertiQoL) tool: development and general psychometric properties

text: Objective To develop the first international instrument to measure fertility quality of life, FertiQoL, in men and women experiencing fertility problems, to evaluate the preliminary psychometric properties of this new tool and to translate FertiQoL into multiple languages. Design Survey. Setting Online and fertility clinics in USA, Australia/New Zealand, Canada, and United Kingdom. Participants A total of 1,414 people with fertility problems. Intervention(s) None. Main Outcome Measure(s) FertiQoL. Result(s) FertiQoL consists of 36 items that assess core (24 items) and treatment-related (10 items) quality of life as well as overall life and physical health (2 items). Cronbach reliability statistics for the Core and Treatment FertiQoL (and subscales) were satisfactory, in the range of 0.72 and 0.92. Sensitivity analyses showed that FertiQoL detected expected relations between quality of life and gender, parity, and support seeking. FertiQoL was translated into 20 languages by the same translation team, with each translation verified by local bilingual fertility experts. Conclusion(s) FertiQoL is a reliable measure of the impact of fertility problems and its treatment on quality of life. Future research should establish its use in cross-cultural research and clinical work.


title: A nationwide survey of Leishmania infantum infection in cats and associated risk factors in Italy

text: Though scantly investigated, Leishmania infantum infection and clinical cases of leishmaniasis in cats have been recently reported in several countries of the Mediterranean basin, with large variability in prevalence data. A major limitation in the comparability of the data available is attributed to the differences in diagnostic techniques employed and cat populations sampled. The aim of this study was to assess the prevalence of L. infantum infection in owned cats across Italy by serological and molecular tests and the identification of potential risk factors. Blood samples from 2,659 cats from northern (n = 1,543), central (n = 471) and southern (n = 645) Italy were tested for antibodies against L. infantum, by an immunofluorescence antibody test and for the parasites’ DNA, by real-time PCR. Samples were additionally screened for feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) proviral DNAs. An overall cumulative L. infantum prevalence of 3.9% was recorded by serology (3.3%) and/or qPCR (0.8%), with a higher rate (10.5%) in southern Italy. The risk of L. infantum infection in cats was significantly associated to the geographical areas (South vs North and Centre; p<0.0001), age class (from 19 months to 6 years old vs ≤18 months old, p = 0.0003), neutering status (not neutered vs neutered, p = 0.0028) and FIV infection (p = 0.0051).Though the role of cats in the epidemiology of L. infantum is still debated, our findings indicate that cats are exposed to and/or infected by this protozoan, mainly in endemic regions of Italy. Hence, a standardization of procedures for a prompt diagnosis of L. infantum infection in cats and for screening cat population is crucial for a better understanding of the epidemiology of feline leishmaniasis, and of the potential role of cats in the transmission cycle of zoonotic visceral leishmaniasis.


title: Management of the slowly emerging zoonosis, Hendra virus, by private veterinarians in Queensland, Australia: a qualitative study

text: BACKGROUND: Veterinary infection control for the management of Hendra virus (HeV), an emerging zoonosis in Australia, remained suboptimal until 2010 despite 71.4% (5/7) of humans infected with HeV being veterinary personnel or assisting a veterinarian, three of whom died before 2009. The aim of this study was to identify the perceived barriers to veterinary infection control and HeV management in private veterinary practice in Queensland, where the majority of HeV outbreaks have occurred in Australia. RESULTS: Most participants agreed that a number of key factors had contributed to the slow uptake of adequate infection control measures for the management of HeV amongst private veterinarians: a work culture characterised by suboptimal infection control standards and misconceptions about zoonotic risks; a lack of leadership and support from government authorities; the difficulties of managing biosecurity and public health issues from a private workforce perspective; and the slow pattern of emergence of HeV. By 2010, some infection control and HeV management changes had been implemented. Participants interviewed agreed that further improvements remained necessary; but also cautioned that this was a complex process which would require time. CONCLUSION: Private veterinarians and government authorities prior to 2009 were unprepared to handle new slowly emerging zoonoses, which may explain their mismanagement of HeV. Slowly emerging zoonoses may be of low public health significance but of high significance for specialised groups such as veterinarians. Private veterinarians, who are expected to fulfil an active biosecurity and public health role in the frontline management of such emerging zoonoses, need government agencies to better recognise their contribution, to consult with the veterinary profession when devising guidelines for the management of zoonoses and to provide them with greater leadership and support. We propose that specific infection control guidelines for the management of slowly emerging zoonoses in private veterinary settings need to be developed.


title: Porcine epidemic diarrhea in China

text: Abstract Porcine epidemic diarrhea (PED) is a contagious intestinal disease caused by Porcine epidemic diarrhea virus (PEDV) that characterized by vomiting, diarrhea, and dehydration. PEDV was first identified in the 1980s in China, and since then, it has become one of the most common viral causes of diarrhea. In October 2010, a large-scale outbreak of PED caused by a PEDV variant occurred in China, resulting in tremendous economic losses. This review presents a comprehensive description of PEDV history, prevalence, molecular features, and prevention and control strategies in China.


title: Disposition of the car☐y-terminus tail of rabbit lactase-phlorizin hydrolase elucidated by phosphorylation with protein kinase A in vitro and in tissue culture

text: Abstract The intracellular disposition of the car☐y-terminus tail of rabbit lactase-phlorizin hydrolase (LPH) is demonstrated, using a specific phosphorylation of Ser1916 by protein kinase A (PKA). This phosphorylation is shown to occur not only in vitro (with pure LPH and pure catalytic subunit of PKA), but also in an organ culture of the small intestine. Cholera toxin, which is known to act in vivo on the membranes of the small intestine, with severe clinical consequences, and to elevate the intracellular cyclic AMP of enterocytes, is shown to enhance significantly the phosphorylation of LPH in intact cells grown as an organ culture. These findings establish the cytosolic orientation of the car☐yterminus tail of LPH in situ, and raise the possibility that the tail itself and its phosphorylation by PKA may have a physiological or physiopathological significance.


COVID‐19: a major cause of cachexia and sarcopenia?


title: The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer

text: The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.


The Nucleocapsid Protein of SARS–CoV-2: a Target for Vaccine Development


title: Preparation for the United States Medical Licensing Examinations in the Face of COVID-19

text: The COVID-19 pandemic has led to the canceling and rescheduling of the United States Medical Licensing Examination (USMLE) examinations due to the nationwide closure of the Prometric testing centers, which poses a significant challenge to medical students. The rescheduling of a high-stakes board examination leads to significant stress and potential burnout. Students may need guidance to decrease anxiety and reframe their study plan while maintaining their knowledge. Here, we combined board examination coaching tips with specific worked examples to describe how to prevent burnout, give recommendations for scheduling, and suggest practical approaches to USMLE and other high-stakes examinations.


title: Land Use Change and Human Health

text: Human activity is dramatically changing the global landscape. These changes in land use and cover are, in turn, altering the dynamics of infectious disease transmission in numerous ways. They are creating new habitat and breeding sites for disease vectors that, in many cases, favor disease transmission. They are leading to direct exposure to pathogens by changing water quality and runoff patterns. They are altering the nature of human–wildlife interactions and creating new exposure routes. Not surprisingly, these changes are occurring coincident with a rise in new or reemerging infectious diseases. These are not merely academic concerns. The diseases impacted by these changes represent a large percentage of the total global burden of disease.


Cardiopulmonary resuscitation in the COVID-19 era – Will the risk-benefit shift in resource-poor settings?


title: Gastrointestinal Diseases of Ferrets

text: Disease of the gastrointestinal (GI) tract is common in ferrets. This chapter reviews diseases of the upper and lower GI tract in ferrets, discusses how to differentiate between causes of diarrhea and vomiting, and provides information to help formulate an appropriate treatment plan. Clinicians should be familiar with the more common GI disorders in ferrets and be able to recognize clinical signs and differentiate among potential diagnoses.


title: GS-5734 and its parent nucleoside analog inhibit Filo-, Pneumo-, and Paramyxoviruses

text: GS-5734 is a monophosphate prodrug of an adenosine nucleoside analog that showed therapeutic efficacy in a non-human primate model of Ebola virus infection. It has been administered under compassionate use to two Ebola patients, both of whom survived, and is currently in Phase 2 clinical development for treatment of Ebola virus disease. Here we report the antiviral activities of GS-5734 and the parent nucleoside analog across multiple virus families, providing evidence to support new indications for this compound against human viruses of significant public health concern.


A novel strategy to generate virus vaccines with expanded genetic codes


title: Estimating the risk of Middle East respiratory syndrome (MERS) death during the course of the outbreak in the Republic of Korea, 2015

text: Summary Objectives A large cluster of the Middle East respiratory syndrome (MERS) linked to healthcare setting occurred from May to July 2015 in the Republic of Korea. The present study aimed to estimate the case fatality ratio (CFR) by appropriately taking into account the time delay from illness onset to death. We then compare our estimate against previously published values of the CFR for MERS, i.e., 20% and 40%. Methods Dates of illness onset and death of the MERS outbreak in the Republic of Korea were extracted from secondary data sources. Using the known distribution of time from illness onset to death and an integral equation model, we estimated the delay-adjusted risk of MERS death for the South Korean cluster. Results Our most up-to-date estimate of CFR for the MERS outbreak in South Korea was estimated at 20.0% (95% confidence intervals (CI): 14.6, 26.2). During the course of the outbreak, estimate of the CFR in real time appeared to have decreased and become significantly lower than 40%. Conclusions The risk of MERS death in Korea was consistent with published CFR. The estimate decreased with time perhaps due to time-dependent increase in case ascertainment. Crude ratio of cumulative deaths to cases underestimates the actual risk of MERS death because of time delay from illness onset to death.


Reply to: Bioactive Lipids and Coronavirus (COVID-19)-further Discussion


title: Immunohistological demonstration of feline infectious peritonitis virus antigen in paraffin-embedded tissues using feline ascites or murine monoclonal antibodies

text: Abstract Feline infectious peritonitis (FIP) virus antigen was demonstrated after methanol, ethanol or formalin fixation in paraffin-embedded tissues by means of monoclonal and polyclonal antibodies. The monoclonal antibody was induced by immunization with transmissible gastroenteritis virus. Polyclonal antibodies were obtained by purification on protein A-Sepharose of ascites fluid from a cat with FIP. Almost all cats diagnosed as suffering from FIP by postmortem and histological examination exhibited FIP virus (FIPV) antigen in macrophages in granulomas whereas FIPV antigen was only once demonstrable in another location.


title: The impact of physical activity on psychological health during Covid-19 pandemic in Italy

text: The worldwide spread of COVID-19 has upset the normality of Italian daily life, forcing population to social distancing and self-isolation. Since the containment precautions also concern sport-related activities, home workout remained the only possibility to play sports and stay active during the pandemic. The present study aimed to examine changes in the physical activity levels during self-quarantine in Italy, and the impact of exercise on psychological health. A total of 2974 Italian subjects has completed an online survey, but only 2524 subjects resulted eligible for this study. The questionnaire measured the total weekly physical activity energy expenditure before and during quarantine (i.e. the sum of walking, moderate-intensity physical activities, and vigorous-intensity physical activities) in Metabolic Equivalent Task minutes per week (MET–min/wk) using an adapted version of International Physical Activity Questionnaire and their psychological well-being using the Psychological General Well Being Index. Of the 2524 Italian subjects included in the study, 1426 were females (56.4%) and 1098 males (43.6%). Total physical activity significantly decreased between before and during COVID-19 pandemic (Mean: 2429 vs. 1577 MET–min/wk, ∗∗∗∗p < 0.0001), in all age groups and especially in men (Female, mean: 1994 vs. 1443 MET–min/wk, ∗∗∗∗p < 0.0001; Male, mean: 2998 vs. 1754 MET–min/wk, ∗∗∗∗p < 0.0001). Furthermore, a significant positive correlation was found between the variation of physical activity and mental well-being (r = 0.07541, ∗∗∗p = 0.0002), suggesting that the reduction of total physical activity had a profoundly negative impact on psychological health and well-being of population. Based on this scientific evidence, maintaining a regular exercise routine is a key strategy for physical and mental health during a forced rest period like the current coronavirus emergency.


title: Residents’ awareness of the role of informal green spaces in a post-industrial city, with a focus on regulating services and urban adaptation potential

text: Abstract Urban green spaces (UGS) and the ecosystem services they provide are essential for the health and wellbeing of city dwellers. UGS are increasingly seen as a potential solution for sustainable urban planning and development. Informal green spaces (IGS), even though they may make up a large share of UGS, are often overlooked in this regard. This study examines residents’ awareness of the ecosystem services provided by IGS and their need for redevelopment. The data were collected through structured interviews in the immediate vicinity of selected IGS in the Polish city of Łódź. Łódź is typical of post-industrial European cities struggling with environmental (heatwaves, cloudbursts), social (aging, depopulation) and spatial (a neglected and dense city center) issues. Our results show that residents saw IGS as places able to provide a range of services, mostly of the regulating type, and even minor design interventions can improve the attractiveness of IGS. Taking this into account, we conclude that IGS are important vegetated areas in the city, which can be complementary to formal greenery.


title: A “possible” involvement of TNF-alpha in apoptosis induction in peripheral blood lymphocytes of cats with feline infectious peritonitis

text: Abstract Feline infectious peritonitis (FIP) cats show a decrease in peripheral blood lymphocyte counts, and a particularly marked decrease in T cells including CD4+ and CD8+ cells. In this study, we showed that lymphopenia observed in FIP cats was due to apoptosis, and that the ascitic fluid, plasma, and culture supernatant of peritoneal exudate cells (adherent cells with macrophage morphology, or PEC) from FIP cats readily induced apoptosis in specific pathogen-free cat peripheral blood mononuclear cells, particularly CD8+ cells. In addition, TNF-alpha released from macrophages and TNF-receptor (TNFR) 1 and TNFR2 mRNA expression in lymphocytes were closely involved in this apoptosis induction. In particular, in CD8+ cells cultured in the presence of the PEC culture supernatant, the expression levels of TNFR1 and TNFR2 mRNA were increased, indicating that CD8+ cells are more susceptible to apoptosis induction by TNF-alpha than other lymphocyte subsets, particularly B cells (CD21+ cells). The results of this study suggest that TNF-alpha, produced by virus-infected macrophages, is responsible for induction of apoptosis in uninfected T cells, primarily CD8+ T cells.


title: BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID‐19 therapy

text: Bruton's tyrosine kinase (BTK) signaling is involved in innate immune responses and regulates the production of proinflammatory cytokines that can contribute to COVID‐19 immunopathology. Clinical trials with BTK inhibitors in COVID‐19 treatment have been proposed, and previous studies have attempted to investigate the therapeutic effects of ibrutinib and underlying mechanisms in treating viral pneumonia. These attempts, however, did not consider potential off target effect of BTK inhibitors on T cell differentiation, function, and survival, which may be beneficial in treatment for COVID‐19. Here, we summarize the current knowledge of BTK/IL‐2‐inducible T‐cell kinase (ITK) signaling in immunopathology and lymphopenia and discuss the potential of BTK/ITK dual inhibitors such as ibrutinib in modulating immunopathology and lymphopenia, for COVID‐19 therapy.


In memory of Michael J. O. Wakelam (1955–2020): a pioneer in lipid signalling and lipidomics


title: Update on molecular techniques for diagnostic testing of infectious disease

text: The era of diagnostic molecular biology has arrived for small animal clinicians, and it is a near certainty that assays such as the PCR and RT-PCR will become more widely available for a wider array of infectious agents. Already there is an extensive list of infectious diseases of dogs and cats that have been investigated with molecular tools. A partial list is included in box 1. An understanding of the advantages and disadvantages of the molecular techniques and some of the questions these techniques can answer for clinicians can serve practitioners well in their approach to the diagnosis of infectious diseases in dogs and cats. It is likely that additional applications of these tools to small animal medicine will become apparent as investigators use and refine them for their research purposes, or as new uses emerge from human medical applications. Clinicians also are likely to reap the benefits of this knowledge. Because samples often are acquired easily from clinical patients in most practice settings, access to these tools puts all clinicians in the group of discoverers of new, or variations of, infectious diseases and their clinical manifestations.


title: Developing WHO rapid advice guidelines in the setting of a public health emergency

text: Abstract Objectives We describe newly established guidance for guideline developers at the World Health Organization (WHO) on the process and procedures for developing a rapid advice guideline in the context of a public health emergency (e.g., the 2014 Ebola epidemic). Study Design and Setting We based our approach on established rapid review methods, which were incorporated into existing WHO guideline development processes. Guidance was further informed by in-depth discussions of issues related to rapid guideline development with WHO staff (n = 6), who oversee the Organization's response to emergencies. Results We discuss criteria for considering if a rapid advice guideline is appropriate and feasible and outline the roles of various contributors across the phases of development. Further, we describe the methods and steps involved in performing rapid reviews, which are more fluid and iterative than for a standard guideline process. In general, rapid advice guidelines involve a shorter timeline, narrower scope, and the use of abbreviated methods for the evidence review. Conclusion Important differences exist between developing a standard guideline and a rapid advice guideline. However, the core principles for WHO guidelines apply to rapid advice guidelines including minimizing bias, applying transparent processes and the use of explicit methods.


title: Hesperetin protects crayfish Procambarus clarkii against white spot syndrome virus infection

text: Abstract Hesperetin is a natural flavanone compound, which mainly exists in lemons and oranges, and has potential antiviral and anticancer activities. In this study, hesperetin was used in a crayfish pathogen challenge to discover its effects on the innate immune system of invertebrates. The crayfish Procambarus clarkii was used as an experimental model and challenged with white spot syndrome virus (WSSV). Pathogen challenge experiments showed that hesperetin treatment significantly reduced the mortality caused by WSSV infection, while the VP28 copies of WSSV were also reduced. Quantitative reverse transcriptase polymerase chain reaction revealed that hesperetin increased the expression of several innate immune-related genes, including NF-kappaB and C-type lectin. Further analysis showed that hesperetin treatment plays a positive effects on three immune parameters like total hemocyte count, phenoloxidase and superoxide dismutase activity. Nevertheless, whether or not infected with WSSV, hesperetin treatment would significantly increase the hemocyte apoptosis rates in crayfish. These results indicated that hesperetin could regulate the innate immunity of crayfish, and delaying and reducing the mortality after WSSV challenge. Therefore, the present study provided novel insights into the potential therapeutic or preventive functions associated with hesperetin to regulate crayfish immunity and protect crayfish against WSSV infection, provide certain theoretical basis for production practice.


title: Cas d’une patiente de grand âge en hospitalisation aiguë pour une atteinte sévère de COVID-19: Aspects moteurs

text: Résumé Le virus SRAS-CoV-2, à l’origine de la pandémie actuelle de COVID-19, engendre des troubles respiratoires aigus qui peuvent conduire à une hospitalisation, essentiellement chez les personnes âgées. Le cas présenté est celui d’une patiente de grand âge présentant une atteinte pulmonaire sévère. Les évaluations motrices quotidiennes sur une semaine comprenaient le test Timed up and go, le test Five sit-to-stand, le test de force de serrage maximal et le recueil des constantes cardio-respiratoires (fréquence cardiaque, respiratoire et saturation en oxygène). Une évaluation cognitive et de la qualité de vie ont aussi été réalisés. Entre l’évaluation initiale et finale, la durée de réalisation du Timed Up and Go a diminué de 4.9 s, la performance au Five sit-to-stand est restée relativement stable, dans un contexte de sevrage de l’oxygène, de maintien de la saturation et d’une augmentation de la fréquence respiratoire. Malgré un pronostic péjoratif, l’amélioration respiratoire de la patiente s’est accompagnée d’améliorations motrices fonctionnelles. Les relations de régulations motrices et cardio-respiratoires sont discutées. Abstract The SARS-CoV-2 virus at the origin of the current COVID-19 pandemic is causing acute respiratory disorders that may lead to hospitalization, mainly in the elderly. The case presented is that of an old age patient with severe lung disease. Daily motor assessments over 1 week included Timed up and go test, the Five sit-to-stand test, the grip test and the collection of cardiorespiratory constants (heart rate, respiratory rate and 02 saturation). A cognitive and quality of life assessments were performed. Between the initial and final evaluation, the time taken to complete the Timed Up and Go decreased by 4.9 sec, the performance at the five sit-to-stand remained relatively stable, in a context of oxygen withdrawal, maintenance of saturation and an increase in respiratory rate. Despite a poor prognosis, the patient's respiratory improvement was accompanied by functional motor improvements. The relationship between motor and cardiorespiratory regulation is discussed.


title: The direction of restructuring of a Korea field epidemiology training program through questionnaire survey among communicable disease response staff in Korea

text: We used a survey about the need for an educational training of infectious disease response staff in Korea Centers for Disease Control and Prevention (KCDC) and officer in metropolitan cities and provincial government to conduct field epidemiological investigation. The survey was conducted from January 25 to March 15, 2016. A total of 173 participants were selected from four different groups as follows: 27 clinical specialists, 22 Epidemic Intelligence Service (EIS) officers, 82 KCDC staff, and 42 local health department officials. Results revealed that 83% of KCDC staff and 95% of local health department officials agreed on the need for educational training to strengthen capability of personnel to conduct epidemic research and investigation. The level of their need for training was relatively high, while self-confidence levels of individuals to conduct epidemic research and investigation was low. It was concluded that there was a need to develop training programs to enhance the ability of public health officials, EIS officers, KCDC staff, and local health department personnel to conduct epidemic research and investigation.


title: Zinc lozenges as cure for the common cold – A review and hypothesis

text: Summary A 7-day reduction in duration of common colds was shown by Eby et al. in 1984 using 23mg zinc gluconate throat lozenges. Over the following 25years, 14 double-blind, placebo-controlled, randomized clinical trials produced widely differing results with about one-half showing success and the remainder showing failure. Positively charged, ionic zinc (iZn), but not bound zinc, is strongly astringent, antirhinoviral, increases interferon-gamma (IFN-γ) 10-fold, inhibits intercellular adhesion molecule-1 (ICAM-1) and inhibits the release of vasoactive ingredients from mast cell granules. Solution equilibrium chemistry analytical techniques showed lozenge iZn fraction varying from 0% to 100% of total lozenge zinc between trials, with zinc acetate (ZA) releasing 100% iZn, zinc gluconate (ZG) releasing 72% iZn and other zinc compounds releasing much less or none at physiologic pH 7.4. Since only iZn has in vitro benefits, iZn variations are hypothesized to have produced the widely varying clinical results. In support of the iZn hypothesis, lozenge iZn and total daily iZn in trials were found highly correlated with reductions in common cold durations with statistical significance for mean duration (P <0.001) and median duration (P <0.004), while total zinc (iZn plus bound) showed no correlation with changes in duration. Duration reductions (mean 0days, median 0.43days) for multi-ligand ZG and ZA lozenges differed significantly from duration reductions (mean 3.37days, median 2.9days) for single ligand ZA and ZG lozenges (P <0.001) showing that additive ligands as flavor-masks damaged or eliminated efficacy. Five of 6 trials with lozenges whose zinc compositions had a first stability constant of 1.7 or less succeeded, while only 2 of 9 trials of lozenges with higher stability succeeded (P <0.02). From the strong, multiple statistical relationships found, it is inferred that iZn is the active ingredient in zinc lozenges for colds, as it is in vitro against rhinoviruses, and that solution chemistry analytical techniques used at physiological pH are correct means for lozenge iZn analysis. Zinc lozenges slowly dissolving in the mouth over a 20–30min period releasing adequate iZn (⩾18mg) used each 2h are hypothesized to shorten common colds by 6–7days, which is a cure for the common cold. Due to inadequate lozenge iZn very few of more than 40 different brands of zinc lozenges on the US market are expected to have any effect on the duration or severity of common colds.


title: A High Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury during the COVID-19 pandemic

text: Drug repurposing is the only method capable of delivering treatments on the shortened time-scale required for patients afflicted with lung disease arising from SARS-CoV-2 infection. Mucin-1 (MUC1), a membrane-bound molecule expressed on the apical surfaces of most mucosal epithelial cells, is a biochemical marker whose elevated levels predict the development of acute lung injury (ALI) and respiratory distress syndrome (ARDS), and correlate with poor clinical outcomes. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce MUC1 protein abundance. Our screen identified Fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, Fostamatinib reduced MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by Fostamatinib promoted MUC1 removal from the cell surface. Our work reveals Fostamatinib as a repurposing drug candidate for ALI and provides the rationale for rapidly standing up clinical trials to test Fostamatinib efficacy in patients with COVID-19 lung injury.


docid: bklpufud

title: Novel Approach to Reduce Transmission of COVID-19 During Tracheostomy

text: ABSTRACT Severe infection involving the novel coronavirus 2019 (COVID-19) has been associated with acute respiratory distress syndrome that subsequently requires patients to be intubated and dependent on mechanical ventilation. In the setting of the recent pandemic, there is a greater need to perform tracheostomy for these patients. With the high transmissibility of the virus, there has been an increasing concern for the development of techniques to perform surgical intervention while mitigating the risk for infecting hospital staff. As more data emerge pertaining to viral shedding in various bodily fluids, it has become more important to give special attention to precautions. In this article, we submit a novel approach for better protection and thus reduced transmission for tracheostomy in a COVID-19 positive patient. Importantly, this technique is functional, easy to set up, and can be used for additional operations that involve risk of aerosolization or droplet exposure to operating room staff.


title: Clinical characteristics, laboratory findings, radiographic signs and outcomes of 61,742 patients with confirmed COVID-19 infection: A systematic review and meta-analysis

text: INTRODUCTION: In the current time where we face a COVID-19 pandemic, there is no vaccine or effective treatment at this time. Therefore, the prevention of COVID-19 and the rapid diagnosis of infected patients is crucial. METHOD: We searched all relevant literature published up to February 28, 2020. We used Random-effect models to analyze the appropriateness of the pooled results. RESULT: Eighty studies were included in the meta-analysis, including 61,742 patients with confirmed COVID-19 infection. 62.5% (95% CI 54.5–79, p < 0.001) of patients had a history of recent travel endemic area or contact with them. The most common symptoms among COVID-19 infected patients were fever 87% (95% CI 73–93, p < 0.001), and cough 68% (95% CI 55.5–74, p < 0.001)), respectively. The laboratory analysis showed that thrombocytosis was present in 61% (95% CI 41–78, p < 0.001) CRP was elevated in 79% (95% CI 65–91, p < 0.001), and lymphopenia in 57.5% (95% CI 42–79, p < 0.001). The most common radiographic signs were bilateral involvement in 81% (95% CI 62.5–87, p < 0.001), consolidation in 73.5% (95% CI 50.5–91, p < 0.001), and ground-glass opacity 73.5% (95% CI 40–90, p < 0.001) of patients. Case fatality rate (CFR) in <15 years old was 0.6%, in >50 years old was 39.5%, and in all range group was 6%. CONCLUSIONS: Fever and cough are the most common symptoms of COVID-19 infection in the literature published to date. Thombocytosis, lymphopenia, and increased CRP were common lab findings although most patients included in the overall analysis did not have laboratory values reported. Among Chinese patients with COVID-19, rates of hospitalization, critical condition, and hospitalization were high in this study, but these findings may be biased by reporting only confirmed cases.


title: Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID‐19 pandemic: The Princess Margaret experience and proposal

text: BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT‐hypo) during the COVID‐19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT‐hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT‐acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005‐2017 were included. Locoregional control (LRC) and distant control (DC) after RT‐hypo, RT‐acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus–positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT‐hypo, RT‐acc, and CCRT, respectively) and 1045 HPV– HNSCC cases (with 263, 451, and 331 receiving RT‐hypo, RT‐acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy‐alone patients were older. The median follow‐up was 4.6 years. RT‐hypo, RT‐acc, and CCRT produced comparable 3‐year LRC and DC for HPV+ T1‐2N0‐N2a disease (seventh edition of the TNM system [TNM‐7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1‐T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1‐2N2c/T3N0‐N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT‐hypo or RT‐acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV– HNSCC, 3‐year LRC and DC were similar with RT‐hypo, RT‐acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT‐hypo and RT‐acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT‐acc (62%) but not RT‐hypo (80%) or CCRT (92%; RT‐hypo vs CCRT: P = .270; RT‐acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT‐hypo or RT‐acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT‐hypo be considered in place of CCRT for HPV+ T1‐T3N0‐N2c (TNM‐7) HNSCCs, HPV– T1‐T2N0 HNSCCs, and select stage III HNSCCs during the COVID‐19 outbreak.


title: A rapid immunochromatographic test strip for detecting rabies virus antibody

text: Abstract An immunochromatographic test strip (ICTS) for detecting antibodies to rabies virus was developed, using colloidal gold particles labeled with rabies virus glycoprotein as the tracer. The assay was evaluated using sera from dogs immunized with various commercial rabies vaccines, or from dogs in the clinics and sera from dogs immunized with vaccines against pathogens other than rabies virus, and negative sera from a wide variety of animal sources, including dogs, mice, and cats which had never been vaccinated. The ICTS was found to be highly specific for antibodies against rabies virus, with a detection limit of 0.5IU/ml as measured by the fluorescent antibody virus neutralization (FAVN) test. Compared with the FAVN test, the specificity and sensitivity of ICTS were 98.2% and 90.4%, respectively. There was an excellent agreement between results obtained by the ICTS and FAVN tests (kappa=0.888). Strips stored at 4°C in a plastic bag with a desiccant retained their specificity and sensitivity for at least 15 months, and strips stored at ambient temperature remained stable for 12 months. The immunochromatographic test strip may therefore be useful for clinical laboratories lacking specialized equipment and for diagnosis in the field for rapid detection of rabies virus-specific antibodies.


title: Grouper TRIM13 exerts negative regulation of antiviral immune response against nodavirus

text: Abstract The tripartite motif (TRIM)-containing proteins have attracted particular attention to their multiple functions in different biological processes. TRIM13, a member of the TRIM family, is a RING domain-containing E3 ubiquitin ligase which plays critical roles in diverse cellular processes including cell death, cancer and antiviral immunity. In this study, a TRIM13 homolog from orange spotted grouper, Epinephelus coioides (EcTRIM13) was cloned and characterized. The full-length of EcTRIM13 cDNA encoded a polypeptide of 399 amino acids which shared 81% identity with TRIM13 homolog from large yellow croaker (Larimichthys crocea). Amino acid alignment analysis showed that EcTRIM13 contained conserved RING finger and B-box domain. Expression patterns analysis indicated that EcTRIM13 was abundant in liver, spleen, kidney, intestine and gill. Moreover, the transcript of EcTRIM13 in grouper spleen was differently regulated after injection with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C). Under fluorescence microscopy, we observed the tubular structure in wild type EcTRIM13 transfected cells, but the RING domain mutant resulted in the fluorescence distribution was changed and the bright punctate fluorescence was evenly situated throughout the cytoplasm, suggesting that the RING domain was essential for its accurate localization. Overexpression of EcTRIM13 in vitro obviously increased the replication of red spotted grouper nervous necrosis virus (RGNNV), and the enhancing effect of EcTRIM13 on virus replication was affected by the RING domain. Furthermore, the ectopic expression of EcTRIM13 not only negatively regulated the interferon promoter activity induced by interferon regulator factor (IRF) 3, IRF7, and melanoma differentiation-associated protein 5 (MDA5), but also decreased the expression of several interferon related factors. In addition, the overexpression of EcTRIM13 also differently regulated the transcription of pro-inflammatory factors. Together, our results firstly demonstrated that fish TRIM13 exerted negative regulation of antiviral response against nodavirus infection.


title: Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature

text: The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.


docid: jspfwuqu

title: The environmental and economic analysis of grid-connected photovoltaic power systems with silicon solar panels, in accord with the new energy policy in Iran

text: Abstract In recent years, authorities in Iran have introduced supporting policies for renewable energy resources but there is no comprehensive and updated survey from this perspective. The aim of this work is to give a comprehensive survey on the country background from energy outlook and its prominent policies for renewable energy resources. Due to the high CO2 emissions alongside with the high solar energy harvesting potential in Iran, We have presented a clear simulation on 20 kW and 1 MW grid-connected photovoltaic (PV) power plants using RETScreen software to determine the environmental and economic aspects based on the net greenhouse gases (GHG) emissions reduction, the annual electricity exported to the grid, the cumulative cash flows, and the payback period for the initial investment. According to this simulation, the annual GHG emissions reduction and the annual electricity exported to the grid for 20 kW and 1 MW PV power plants are 22.06 tCO2, 1103 tCO2, 39 MWh, and 1953 MWh, respectively. From the economic outlook, based on the new feed-in tariff for power plants and the supposed initial costs, the payback period for the initial investments are between 3 and 4, and 5 years for 20 kW and 1 MW PV power plants, respectively.


title: Homologous Recombination as an Evolutionary Force in African Swine Fever Viruses

text: Recent outbreaks of African swine fever virus (ASFV) in China severely influenced the swine industry of the country. Currently, there is no effective vaccine or drugs against ASFVs. How to effectively control the virus is challenging. In this study, we have analyzed all the publicly available ASFV genomes and demonstrated that there was a large genetic diversity of ASFV genomes. Interestingly, the genetic diversity was mainly caused by extensive genomic insertions and/or deletions (indels) instead of the point mutations. The genomic diversity of the virus resulted in proteome diversity. Over 250 types of proteins were inferred from the ASFV genomes, among which only 144 were observed in all analyzed viruses. Further analyses showed that the homologous recombination may contribute much to the indels, as supported by significant associations between the occurrence of extensive recombination events and the indels in the ASFV genomes. Repeated elements of dozens of nucleotides in length were observed to widely distribute and cluster in the adjacent positions of ASFV genomes, which may facilitate the occurrence of homologous recombination. Moreover, two enzymes, which were possibly related to the homologous recombination, i.e., a Lambda-like exonuclease with a YqaJ-like viral recombinase domain, and a DNA topoisomerase II, were found to be conservative in all the analyzed ASFVs. This work highlighted the importance of the homologous recombination in the evolution of the ASFVs, and helped with the strategy development of the prevention and control of the virus.


title: The use of genomics in microbial vaccine development

text: Vaccination is one of the most effective tools for the prevention of infectious diseases. The availability of complete genome sequences, together with the progression of high-throughput technologies such as functional and structural genomics, has led to a new paradigm in vaccine development. Pan-genomic reverse vaccinology, with the comparison of sequence data from multiple isolates of the same species of a pathogen, increases the opportunity of the identification of novel vaccine candidates. Overall, the conventional empiric approach to vaccine development is being replaced by vaccine design. The recent development of synthetic genomics may provide a further opportunity to design vaccines.


title: Predicting Interactions between Virus and Host Proteins Using Repeat Patterns and Composition of Amino Acids

text: Previous methods for predicting protein-protein interactions (PPIs) were mainly focused on PPIs within a single species, but PPIs across different species have recently emerged as an important issue in some areas such as viral infection. The primary focus of this study is to predict PPIs between virus and its targeted host, which are involved in viral infection. We developed a general method that predicts interactions between virus and host proteins using the repeat patterns and composition of amino acids. In independent testing of the method with PPIs of new viruses and hosts, it showed a high performance comparable to the best performance of other methods for single virus-host PPIs. In comparison of our method with others using same datasets, our method outperformed the others. The repeat patterns and composition of amino acids are simple, yet powerful features for predicting virus-host PPIs. The method developed in this study will help in finding new virus-host PPIs for which little information is available.


Large-scale mapping of the Ebola NP and GP proteins reveals multiple immunoprevalent and conserved CD4 T-cell epitopes


title: Evaluación de la teleconsulta en el paciente urológico durante la pandemia COVID 19

text: Abstract Introduction: The global pandemic of COVID-19 has led to rapid implementation of telemedicine, but there is little information on patient satisfaction of this system as an alternative to face-to-face care. Objective. To evaluate urological patient satisfaction with teleconsultation during the COVID-19 pandemic. Material and methods: Observational, prospective, cross-sectional, non-interventional study carried out by telephone survey during the period considered as the peak of the pandemic (March-April 2020). A quality survey composed of 11 questions on urological care provided by physicians during the COVID-19 pandemic was conducted, selecting a representative sample of patients attended by teleconsultation. Results: Two hundred patients were contacted by telephone to answer a survey on the quality of teleconsultation. The distribution of patients surveyed among the specialized consultations was homogeneous with the number of consultations cited in the period;18% of them required assistance from family members. Sixty percent of patients avoided going to a medical center during the pandemic. Of the surveyed patients, 42% had cancelled diagnostic tests, 59% had cancelled medical consultations, 3.5% had cancelled treatments and 1%, had cancelled interventions. Ten percent reported a worsening of urological symptoms during confinement. According to physicians, consultations were effectively delivered in 72% of cases, with teleconsultation being carried out by their usual urologist in 81%. Teleconsultation overall satisfaction level was 9 (IQI 8-10), and 61.5% of respondents consider teleconsultation as a "health care option" after the healthcare crisis. Conclusion: Teleconsultation has been evaluated with a high level of satisfaction during the COVID-19 pandemic, offering continuous care to urological patients during the healthcare crisis. The perceived quality offers a field of optional telematic assistance in selected patients, which should be re-evaluated in a period without confinement measures.


title: Severe acute respiratory syndrome coronavirus accessory protein 9b is a virion-associated protein

text: Abstract Eight accessory proteins have been identified in severe acute respiratory syndrome-associated coronavirus (SARS-CoV). They are believed to play roles in the viral life cycle and may contribute to the pathogenesis and virulence. ORF9b as one of these accessory proteins is located in subgenomic mRNA9 and encodes a 98 amino acid protein. However, whether 9b protein is a structural component of SARS-CoV particles remains unknown. In this study, we demonstrate that 9b protein is translated from bicistronic mRNA9 via leaky ribosome scanning and it is incorporated into both virus-like particles (VLPs) and purified SARS-CoV virions. Further analysis shows that sufficient incorporation of 9b protein into VLPs is dependent upon the co-expression of E and M proteins, but not upon the presence of either S or N protein. Our data indicate that 9b protein of SARS-CoV is another virion-associated accessory protein. This finding will lead to a better understanding of the properties of the SARS-CoV 9b protein.


title: Nuclear proteins hijacked by mammalian cytoplasmic plus strand RNA viruses

text: Abstract Plus strand RNA viruses that replicate in the cytoplasm face challenges in supporting the numerous biosynthetic functions required for replication and propagation. Most of these viruses are genetically simple and rely heavily on co-opting cellular proteins, particularly cellular RNA-binding proteins, into new roles for support of virus infection at the level of virus-specific translation, and building RNA replication complexes. In the course of infectious cycles many nuclear-cytoplasmic shuttling proteins of mostly nuclear distribution are detained in the cytoplasm by viruses and re-purposed for their own gain. Many mammalian viruses hijack a common group of the same factors. This review summarizes recent gains in our knowledge of how cytoplasmic RNA viruses use these co-opted host nuclear factors in new functional roles supporting virus translation and virus RNA replication and common themes employed between different virus groups.


title: Potential use of hydroxychloroquine, ivermectin and azithromycin drugs in fighting COVID-19: trends, scope and relevance

text: Abstract Alarming situation has been caused due to the emergence of COVID-19 infection around the world. There is an urgency of developing a therapeutic strategy in order to control the spread of COVID-19. Towards that initiative, potential drugs like hydroxychloroquine, ivermectin and azithromycin have been tested by diverse group of researchers worldwide for their potential against novel coronavirus. The present report presents together the comprehensive knowledge derived from the major researches about the above drugs altogether in context of the current health emergency around the world. Hydroxychloroquine and ivermectin were known to act by creating the acidic environment and inhibiting the importin (IMPα/β1) mediated viral import. Azithromycin was found to act similar to the hydroxychloroquine as an acidotropic lipophilic weak base. All the three categories of drugs seemed to potentially act against novel coronavirus infection. However, their efficacies need to be studied in detail individually and in combination in-vivo in order to combat COVID-19 infection.


title: e-Tourism beyond COVID-19: a call for transformative research

text: This viewpoint article argues that the impacts of the novel coronavirus COVID-19 call for transformative e-Tourism research. We are at a crossroads where one road takes us to e-Tourism as it was before the crisis, whereas the other holds the potential to transform e-Tourism. To realize this potential, e-Tourism research needs to challenge existing paradigms and critically evaluate its ontological and epistemological foundations. In light of the paramount importance to rethink contemporary science, growth, and technology paradigms, we present six pillars to guide scholars in their efforts to transform e-Tourism through their research, including historicity, reflexivity, equity, transparency, plurality, and creativity. We conclude the paper with a call to the e-Tourism research community to embrace transformative research.


title: Initial events in the pathogenesis of acute tonsillitis caused by Streptococcus pyogenes 1 This paper was presented in part at the XVI World Congress of Otorhinolaryngology, Head and Neck Surgery, Sydney, Australia, March 2–7, 1997. 1

text: Abstract Bacterial and epithelial cell samples were obtained, within 24 h of onset of pharyngeal symptoms, from the palatine tonsils of nine patients (four female and five male; age range 10–40 years, median age 23) with acute tonsillitis, culture-positive for Streptococcus pyogenes. The specimens were examined using fluorescein isothiocyanate- (FITC) and gold-labelled antiserum to S. pyogenes and fluorescence, scanning electron and transmission electron microscopy. S. pyogenes could be identified both in the mucous layer covering the tonsils and attached to the surface epithelial cells. Long chains of coccus-shaped bacteria could be seen encroaching on the epithelial cell borders. S. pyogenes can apparently penetrate the mucous barrier, attach to the epithelial cells, spread from cell to cell and possibly penetrate into the outermost layer of the epithelial cells. These events in turn provoke cytokine production and/or complement activation, which induce inflammatory reaction in the tonsillar tissue.


title: Comparative study of synonymous codon usage variations between the nucleocapsid and spike genes of coronavirus, and C-type lectin domain genes of human and mouse

text: Coronaviruses (CoVs) are single-stranded RNA viruses which contain the largest RNA genomes, and severe acute respiratory syndrome coronavirus (SARS-CoV), a newly found group 2 CoV, emerged as infectious disease with high mortality rate. In this study, we compared the synonymous codon usage patterns between the nucleocapsid and spike genes of CoVs, and C-type lectin domain (CTLD) genes of human and mouse on the codon basis. Findings indicate that the nucleocapsid genes of CoVs were affected from the synonymous codon usage bias than spike genes, and the CTLDs of human and mouse partially overlapped with the nucleocapsid genes of CoVs. In addition, we observed that CTLDs which showed the similar relative synonymous codon usage (RSCU) patterns with CoVs were commonly derived from the human chromosome 12, and mouse chromosome 6 and 12, suggesting that there might be a specific genomic region or chromosomes which show a more similar synonymous codon usage pattern with viral genes. Our findings contribute to developing the codon-optimization method in DNA vaccines, and further study is needed to determine a specific correlation between the codon usage patterns and the chromosomal locations in higher organisms.


title: Relationship Between Clinical Features and Computed Tomographic Findings in Hospitalized Adult Patients With Community-Acquired Pneumonia

text: Abstract Background Data on the relationship between the clinical and microbiological features of community-acquired pneumonia (CAP) and its computed tomography (CT) findings are limited. The aim of the present study was to investigate the clinic-microbiological features of patients with CAP presenting with ground-glass opacity (GGO) and centrilobular nodules or tree-in-bud pattern on CT images. Methods Patients with CAP who underwent a CT scan at presentation were retrospectively classified using CT findings into consolidation, GGO and bronchiolitis groups. These 3 groups were compared in terms of clinical parameters and microbiological data. Results A total of 40 patients (2.4%) were allocated to the bronchiolitis group and 46 (2.8%) to the GGO group. The most common pathogen in the bronchiolitis group was Mycoplasma pneumoniae, which was significantly more frequently isolated in this group. The bronchiolitis group was characterized by a higher percentage of cough, a lower percentage of chest pain and lower blood levels of inflammatory markers. Common pathogens in the GGO group were not significantly different from those in the other 2 groups. Unlike that observed in the consolidation group, complicated parapneumonic effusion or empyema was not observed in the bronchiolitis or GGO group. Outcome variables were similar in the 3 groups. Conclusions The bronchiolitis group was characterized by a higher frequency of M. pneumoniae and a less severe form of CAP. The GGO and consolidation groups was similar with respect to causative microorganisms and the clinical features of CAP. No patient in the bronchiolitis or GGO group exhibited complicated parapneumonic effusion or empyema.