title: Current Vaccination Strategies in Puppies and Kittens

text: Motivation in writing this article stems from many things: a lack of time spent in the veterinary curriculum discussing vaccines, a growing concern(by the general public and the veterinary community) regarding adverse reactions associated with vaccines, and a desire to prevent a recurrence of preventable infectious diseases resulting from a fear-driven cessation of vaccine administration. The objectives of this article are to present a basic review of immunology as related to vaccines, to discuss general guidelines for pediatric vaccines in canine and feline patients,and to offer suggestions as to how we can most positively influence our patients' health from the first visit.


title: Human bocavirus infection in a neonatal intensive care unit

text: Summary Human bocavirus (HBoV) plays a non-insignificant role as a pathogen in respiratory tract diseases in the pediatric population, especially in infants younger than 2 years of age. In this paper, we have described two cases of a possible nosocomial infection in a neonatal intensive care unit being HBoV the sole detected respiratory virus in clinical samples.


title: Identification of nsp1 gene as the target of SARS‐CoV‐2 real‐time RT‐PCR using nanopore whole genome sequencing

text: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the COVID‐19 pandemic. Accurate detection of SARS‐CoV‐2 using molecular assays is critical for patient management and the control of the COVID‐19 pandemic. However, there is an increasing number of SARS‐CoV‐2 viruses with mutations at the primer or probe binding sites, and these mutations may affect the sensitivity of currently available real‐time reverse transcription–polymerase chain reaction (RT‐PCR) assays targeting the N, E, and ORF1a/b genes. Using sequence‐independent single‐primer amplification (SISPA) and nanopore whole‐genome sequencing, we have found that the nsp1 gene, located at the 5’ end of the SARS‐CoV‐2 genome, was highly expressed in the nasopharyngeal or saliva specimens of 9 COVID‐19 patients of different clinical severity. Based on this finding, we have developed a novel nsp1 real‐time RT‐PCR assay. The primers and probes are highly specific for SARS‐CoV‐2. Validation with 101 clinical specimens showed that our nsp1 RT‐PCR assay has a sensitivity of 93.1% (95% confidence interval, 86.2‐97.2%), which was similar to those of N and E gene RT‐PCR assays. The diagnostic specificity was 100% (95% CI, 92.9‐100%). The addition of nsp1 for multi‐target detection of SARS‐CoV‐2 can avoid false negative results due to mutations at the primers/probes binding sites of currently available RT‐PCR assays. This article is protected by copyright. All rights reserved.


title: Impact of Alignment between Social Media and Business Processes on SMEs’ Business Process Performance: A Conceptual Model

text: Abstract The development of information technology highly affects various business sectors including Small and Medium Enterprises (SMEs). Social media implementation, as one of the most widely used IT application, is expected to support SMEs’ performances. Many types of research in social media have focused on the impact of its implementation on the performance of an organization at a macro level. Research that investigates the linkage between social media and how the company performs its business process is lacking in the literature to date. This study aims to fill this gap by conducting a literature review on social media implementation particularly in SMEs. The result of this study is a conceptual model that follows the proposition of Task-Technology Fit in exploring the impact of social media on SMEs business process performances. As a technology, social media functionality must fit the tasks that SMEs must perform. The model proposed social media alignment with business process domain based on the Process Classification Framework (PCF). The performances are measured at a business process level using four indicators i.e. cost, time, quality and flexibility of the business process.


title: Biochemical terrorism: the medical threat in the twenty-first century

text: Abstract September 11, 2001, forever changed the landscape surrounding terrorism. The oceans no longer protected the United States from terrorists. And as incidences in the Philippines, Spain, Iraq, and other corners of the globe have found, no place on the planet can be considered risk-free. Unfortunately, not only must the world be concerned with acts of violence and destruction, but also with the threat of a more insidious nature—chemical and biological terrorism. According to a March 29, 2004, article in the New York Times, the Pentagon released parts of an unclassified document suggesting that the United States is “woefully ill-prepared to detect and respond to a bioterrorist assault.” In this article, our authors offer us a first-hand window into an important and regrettably necessary area of medicine that could affect us both as physicians and citizens in the twenty-first century. Fig 1 —The Editors Biochemical terrorism—the deliberate dispersion of viruses, bacteria, fungi, and organic or inorganic toxin agents, to kill, mutilate, and create chaos—is a real threat that all countries must cope with today. Both sovereign nations and terror organizations now have the capability to produce and use biochemical agents, and some of them have already demonstrated their eagerness to do so. The development of instant communication has been a further inducement to the terrorists. Each event is reported almost immediately in the media, bringing recognition and reputation to the executors (1–3).


title: From fish to man: understanding endogenous remyelination in CNS demyelinating diseases

text: In the central nervous system (CNS) of man, evolutionary pressure has preserved some capability for remyelination while axonal regeneration is very limited. In contrast, two efficient programmes of regeneration exist in the adult fish CNS, neurite regrowth and remyelination. The rapidity of CNS remyelination is critical since it not only restores fast conduction of nerve impulses but also maintains axon integrity. If myelin repair fails, axons degenerate, leading to increased disability. In the human CNS demyelinating disease Multiple Sclerosis (MS), remyelination often takes place in the midst of inflammation. Here, we discuss recent studies that address the innate repair capabilities of the axon-glia unit from fish to man. We propose that expansion of this research field will help find ways to maintain or enhance spontaneous remyelination in man.


docid: wzcaugst

title: Coronavirus infections reported by ProMED, February 2000–January 2020

text: Abstract Introduction Sources describing the global burden of emerging diseases accurately are still limited. We reviewed coronavirus infections reported by ProMED and assessed the reliability of the data retrieved compared to published reports. We evaluated the effectiveness of ProMED as a source of epidemiological data on coronavirus. Methods Using the keyword “coronavirus” in the ProMED search engine, we reviewed all the information from the reports and collected data using a structured form, including year, country, gender, occupation, the number of infected individuals, and the number of fatal cases. Results We identified 109 entries reported between February 29, 2000 and January 22, 2020. A total of 966 cases were reported, with death reported in 188 cases, suggesting an overall case fatality rate (CFR) of 19.5%. Of 70 cases for which the gender was reported, 47 (67.1%) were male. Most of the cases were reported from China, the United Arab Emirates, and Saudi Arabia, with reports from other countries, including imported cases in Europe and North America. Conclusions Internet-based reporting systems such as ProMED are useful to gather information and synthesize knowledge on emerging infections. Although certain areas need to be improved, ProMED provided useful information about coronaviruses especially during outbreaks.


title: Renin‐angiotensin system revisited

text: New components and functions of the renin‐angiotensin system (RAS) are still being unravelled. The classical RAS as it looked in the middle 1970s consisted of circulating renin, acting on angiotensinogen to produce angiotensin I, which in turn was converted into angiotensin II (Ang II) by angiotensin‐converting enzyme (ACE). Ang II, still considered the main effector of RAS was believed to act only as a circulating hormone via angiotensin receptors, AT1 and AT2. Since then, an expanded view of RAS has gradually emerged. Local tissue RAS systems have been identified in most organs. Recently, evidence for an intracellular RAS has been reported. The new expanded view of RAS therefore covers both endocrine, paracrine and intracrine functions. Other peptides of RAS have been shown to have biological actions; angiotensin 2–8 heptapeptide (Ang III) has actions similar to those of Ang II. Further, the angiotensin 3–8 hexapeptide (Ang IV) exerts its actions via insulin‐regulated amino peptidase receptors. Finally, angiotensin 1–7 (Ang 1–7) acts via mas receptors. The discovery of another ACE2 was an important complement to this picture. The recent discovery of renin receptors has made our view of RAS unexpectedly complex and multilayered. The importance of RAS in cardiovascular disease has been demonstrated by the clinical benefits of ACE inhibitors and AT1 receptor blockers. Great expectations are now generated by the introduction of renin inhibitors. Indeed, RAS regulates much more and diverse physiological functions than previously believed.


Covid-19: junior doctor calls on colleagues to gather supplies for staff working long hours.


title: COVID-19: The potential treatment of pulmonary fibrosis associated with SARS-CoV-2 infection

text: In December 2019, a novel coronavirus, SARS-CoV-2, appeared, causing a wide range of symptoms, mainly respiratory infection. In March 2020, the World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a pandemic, therefore the efforts of scientists around the world are focused on finding the right treatment and vaccine for the novel disease. COVID-19 has spread rapidly over several months, affecting patients across all age groups and geographic areas. The disease has a diverse course; patients may range from asymptomatic to those with respiratory failure, complicated by acute respiratory distress syndrome (ARDS). One possible complication of pulmonary involvement in COVID-19 is pulmonary fibrosis, which leads to chronic breathing difficulties, long-term disability and affects patients’ quality of life. There are no specific mechanisms that lead to this phenomenon in COVID-19, but some information arises from previous severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS) epidemics. The aim of this narrative review is to present the possible causes and pathophysiology of pulmonary fibrosis associated with COVID-19 based on the mechanisms of the immune response, to suggest possible ways of prevention and treatment.


title: Age‐ and infection‐related maturation of the nasal immune response in 0–2‐year‐old children

text: Background: The hygiene hypothesis suggests that exposure to micro‐organisms influences development of the immune system in children. Methods: In this study, we examined nasal immune responses in the first 2 years of life in relation to age of children and the number of viral infections they have experienced. Nasal brushes were taken during rhinovirus‐ (n = 20) or respiratory syncytial virus (RSV)‐induced (n = 7) upper respiratory tract infections (URTI), and of controls (n = 40). Results: The number of macrophages were higher during URTI and increased with age. The number of T lymphocytes increased with age in controls and were higher during URTI at all ages. We found an age‐related decrease in the number of interleukin (IL)‐4‐ and IL‐10‐positive cells in controls, while the number of IL‐12‐positive cells remained unchanged. Changes in T lymphocyte and IL‐4 cell number were stronger related to the age of the child than to the number of respiratory infections, while the opposite was true for macrophages. Conclusions: In infants, we found an infection‐ and age‐related increase respectively for nasal macrophages and T lymphocytes during URTI. Furthermore, the number of IL‐4‐ and IL‐10‐positive cells decreased with age. Whether this maturation reflects a natural age‐related maturation, the degree of exposure to respiratory infections, or possibly both, could not be resolved and needs further study.


title: Discrepancies between feline coronavirus antibody and nucleic acid detection in effusions of cats with suspected feline infectious peritonitis

text: Abstract Intra-vitam diagnosis of feline infectious peritonitis (FIP) is a challenge for veterinary diagnosticians, since there are no highly specific and sensitive assays currently available. With the aim to contribute to fill this diagnostic gap, a total of 61 effusions from cats with suspected effusive FIP were collected intra-vitam for detection of feline coronavirus (FCoV) antibodies and RNA by means of indirect immunofluorescence (IIF) assay and real-time RT-PCR (qRT-PCR), respectively. In 5 effusions there was no evidence for either FCoV RNA or antibodies, 51 and 52 specimens tested positive by IIF and qRT-PCR, respectively, although antibody titres≥1:1600, which are considered highly suggestive of FIP, were detected only in 37 effusions. Three samples with high antibody levels tested negative by qRT-PCR, whereas 18 qRT-PCR positive effusions contained no or low-titre antibodies. qRT-PCR positive samples with low antibody titres mostly contained low FCoV RNA loads, although the highest antibody titres were detected in effusions with C T values>30. In conclusion, combining the two methods, i.e., antibody and RNA detection would help improving the intra-vitam diagnosis of effusive FIP.


Challenging clinical and organizational scenarios in cardiovascular diseases during the SARS-CoV-2 pandemic in Poland. Can we do better?


title: Management Strategies for Cancer Patients in the Time of COVID-19 Pandemic

text: Coronavirus disease 2019 commonly designated as COVID-19 has been declared by World health Organisation (WHO) as a pandemic on 11 March 2020. ‘Lock down’ is found to be the only effective method to control this outbreak and due to the contagious nature of this disease most of the hospitals have stopped elective interventions. Cancer is a second leading cause of death globally and the bystander victims in this scenario are the patients with suspected and proven cancer. Head and neck cancer has a survival rate of 40% to 50% after definitive therapy and the delay in treatment for even 1-2 months may lead to inoperability and poorer outcomes. On contacting the colleagues in different countries, it was found that different strategies have been adapted to prioritize cancer patients. Hence, such type of measures appropriately amended can be implemented as soon as possible to avoid harm to cancer patients.


O.7.8 Burden of disease due to human coronavirus NL63 infections in children under 3 years of age


title: Neurological associations of COVID-19

text: BACKGROUND: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a scale not seen since the 1918 influenza pandemic. Although the predominant clinical presentation is with respiratory disease, neurological manifestations are being recognised increasingly. On the basis of knowledge of other coronaviruses, especially those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome epidemics, cases of CNS and peripheral nervous system disease caused by SARS-CoV-2 might be expected to be rare. RECENT DEVELOPMENTS: A growing number of case reports and series describe a wide array of neurological manifestations in 901 patients, but many have insufficient detail, reflecting the challenge of studying such patients. Encephalopathy has been reported for 93 patients in total, including 16 (7%) of 214 hospitalised patients with COVID-19 in Wuhan, China, and 40 (69%) of 58 patients in intensive care with COVID-19 in France. Encephalitis has been described in eight patients to date, and Guillain-Barré syndrome in 19 patients. SARS-CoV-2 has been detected in the CSF of some patients. Anosmia and ageusia are common, and can occur in the absence of other clinical features. Unexpectedly, acute cerebrovascular disease is also emerging as an important complication, with cohort studies reporting stroke in 2–6% of patients hospitalised with COVID-19. So far, 96 patients with stroke have been described, who frequently had vascular events in the context of a pro-inflammatory hypercoagulable state with elevated C-reactive protein, D-dimer, and ferritin. WHERE NEXT? Careful clinical, diagnostic, and epidemiological studies are needed to help define the manifestations and burden of neurological disease caused by SARS-CoV-2. Precise case definitions must be used to distinguish non-specific complications of severe disease (eg, hypoxic encephalopathy and critical care neuropathy) from those caused directly or indirectly by the virus, including infectious, para-infectious, and post-infectious encephalitis, hypercoagulable states leading to stroke, and acute neuropathies such as Guillain-Barré syndrome. Recognition of neurological disease associated with SARS-CoV-2 in patients whose respiratory infection is mild or asymptomatic might prove challenging, especially if the primary COVID-19 illness occurred weeks earlier. The proportion of infections leading to neurological disease will probably remain small. However, these patients might be left with severe neurological sequelae. With so many people infected, the overall number of neurological patients, and their associated health burden and social and economic costs might be large. Health-care planners and policy makers must prepare for this eventuality, while the many ongoing studies investigating neurological associations increase our knowledge base.


title: Blood MxA protein as a marker for respiratory virus infections in young children

text: Abstract Background Type I interferon induced MxA response can differentiate viral from bacterial infections, but MxA responses in rhinovirus or asymptomatic virus infections are not known. Objective To study MxA protein levels in healthy state and during respiratory virus infection of young children in an observational prospective cohort. Study design Blood samples and nasal swabs were collected from 153 and 77 children with and without symptoms of respiratory infections, respectively. Blood MxA protein levels were measured by an enzyme immunoassay and PCR methods were used for the detection of respiratory viruses in nasal swabs. Results Respiratory viruses were detected in 81% of symptomatic children. They had higher blood MxA protein levels (median [interquartile range]) than asymptomatic virus-negative children (695 [345–1370] μg/L vs. 110 [55–170] μg/L; p <0.001). Within asymptomatic children, no significant difference was observed in MxA responses between virus-positive and virus-negative groups. A cut-off level of 175μg/L had 92% sensitivity and 77% specificity for a symptomatic respiratory virus infection. Rhinovirus, respiratory syncytial virus, parainfluenza virus, influenza virus, coronavirus, and human metapneumovirus infections were associated with elevated MxA responses. Asymptomatic virus-negative children vaccinated with a live virus vaccine had elevated MxA protein levels (240 [120–540] μg/L), but significantly lower than children with an acute respiratory infection, who had not received vaccinations (740 [350–1425] μg/L; p <0.001). Conclusion Blood MxA protein levels are increased in young children with symptomatic respiratory virus infections, including rhinovirus infections. MxA is an informative general marker for the most common acute virus infections.


title: Clinical trials with oncolytic reovirus: Moving beyond phase I into combinations with standard therapeutics

text: It is time for those working on oncolytic viruses to take stock of the status of the field. We now have at our disposal an array of potential therapeutic agents, and are beginning to conduct early-phase clinical trials in patients with relapsed/metastatic cancers. By drawing on lessons learned during the development of other biological therapies, such as monoclonal antibodies and targeted small molecule inhibitors, we are now in a position to chart the course of the next wave of trials that will go beyond the phase I studies of safety and feasibility. In this article we review our approach to the development of oncolytic viruses as cancer therapeutics. In doing so, we emphasise the fact that this process is modular and involves multiple iterative steps between the laboratory and the clinic. Ultimately, at least in the medium term, the future of oncolytic virotherapy lies in combination regimens with standard anti-cancer agents such as radiation and chemotherapy.


Acute pulmonary embolism mimicking COVID – 19 pneumonia


title: Avian influenza A (H5N1) infection: targets and strategies for chemotherapeutic intervention

text: In an avian flu pandemic, which drugs could be used to treat or prevent infection with influenza A (H5N1) virus? Foremost are the viral neuraminidase inhibitors oseltamivir and zanamivir, which have already been used to treat human influenza A (H1N1 and H3N2) and B virus infections. The use of the M2 ion channel blockers amantadine and rimantadine is compounded by the rapid development of drug resistance. Although formally approved for other indications (i.e. treatment of hepatitis C), ribavirin and pegylated interferon might also be useful for controlling avian flu. Combined use of the currently available drugs should be taken into account and attempts should be made to develop new strategies directed at unexplored targets such as the viral proteins hemagglutinin, the viral polymerase (and endonuclease) and the non-structural protein NS1. As has been shown for other viral infections, RNA interference could be a powerful means with which to suppress the replication of avian H5N1.


title: Insights into RNA synthesis, capping, and proofreading mechanisms of SARS-coronavirus

text: Abstract The successive emergence of highly pathogenic coronaviruses (CoVs) such as the Severe Acute Respiratory Syndrome (SARS-CoV) in 2003 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 has stimulated a number of studies on the molecular biology. This research has provided significant new insight into functions and activities of the replication/transcription multi-protein complex. The latter directs both continuous and discontinuous RNA synthesis to replicate and transcribe the large coronavirus genome made of a single-stranded, positive-sense RNA of ∼30kb. In this review, we summarize our current understanding of SARS-CoV enzymes involved in RNA biochemistry, such as the in vitro characterization of a highly active and processive RNA polymerase complex which can associate with methyltransferase and 3′–5′ exoribonuclease activities involved in RNA capping, and RNA proofreading, respectively. The recent discoveries reveal fascinating RNA-synthesizing machinery, highlighting the unique position of coronaviruses in the RNA virus world.


title: Role of multiplex PCR analysis in children with febrile seizures

text: BACKGROUND: The aim of this study was to assess multiplex PCR analysis in detecting causative viruses in children with febrile seizures. METHODS: The study was a retrospective analysis comparing data from a pre-multiplex era (2009) with a period after the introduction of routine respiratory multiplex analysis (2010–2013) in children with febrile seizures. RESULTS: We included 200 children with febrile seizures (mean age: 29.5 ± 1.4.months; 104 male) in the study. In 2009, in 10 out of 49 (20 %) children, microbiology testing (bacterial/fungal) was positive compared with a rate of 74 out of 151 (49 %) children during 2010–2013 (p < 0.01). The rate of positive virological studies increased from 10 (20 %) in 2009 to 73 (48.3 %) in the period 2010–2013 (p < 0.01). Multiplex PCR analysis confirmed viral infections in 52 of 73 cases (71.2 %). CONCLUSION: Routine multiplex PCR analysis fosters the detection of respiratory viruses in children with febrile seizure. The precise role of multiplex analysis in the management of these children awaits further clarification.


title: Benefits, barriers, and incentives for improved resilience to disruption in university teaching

text: Pandemics, earthquakes, fire, war, and other disasters place universities at risk. Disasters can disrupt learning and teaching (L&T) for weeks to months or longer. Some institutions have developed business continuity plans to protect key organisational services and structures, allowing L&T to continue. However, little research touches on how academics, learners, and communities of practice might respond before, during, and after disasters and how their resilience to disruption can be fostered to reduce impacts on L&T. In this research, we investigated academics’ perceptions of building resilience to major L&T disruptions in the New Zealand context. Specifically, we explored how academics characterise a resilient academic and institution, and identified the benefits, barriers, and incentives to building resilience. We used a pragmatic theoretical approach with a mixed methods methodology, to categorise the results within three distinct levels (individual, school/department, and institution), supporting the design and implementation of resilience-building strategies for academics and institutional leaders. We found that support, community, leadership, and planning at universities are critical in building and inhibiting resilience. Participants reported several ‘high impact’ incentives, addressing multiple barriers, that could be used to kick-start resilience. Online and flexible learning are key opportunities for resilience-building, but universities should not underestimate the importance of face-to-face interactions between staff and learners. Our results provide a strong starting point for practitioners and researchers aiming to understand how universities can foster resilience to major disruptions and disasters on university teaching.


title: Viral load quantitation of SARS-coronavirus RNA using a one-step real-time RT-PCR

text: Summary Introduction Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first occurred in humans in the People's Republic of China in November 2002 and has subsequently spread worldwide. A novel virus belonging to the Coronaviridae family has been identified as the cause of this pulmonary disease. The severity of the disease combined with its rapid spread requires the development of fast and sensitive diagnostic assays. Results A real-time quantitative RT-PCR was designed in the nsp11 region of the replicase 1B domain of the SARS-coronavirus (SARS-CoV) genome. To evaluate this quantitative RT-PCR, cRNA standards were constructed by in vitro transcription of SARS-CoV Frankfurt 1 RNA using T7 RNA polymerase, followed by real-time RT-PCR. The assay allowed quantitation over a range of 102 to 108 RNA copies per reaction. Conclusions Extrapolated to clinical samples, this novel assay has a detection range of 104 to 1010 copies of viral genome equivalents per millilitre. In comparison to the current de facto cRNA Artus Biotech standard, the in-house cRNA standard gives a 100-fold higher absolute quantity, suggesting a possible underestimation of the viral load when using the Artus Biotech standard.


docid: drtmapyr

title: Borderless collaboration is needed for COVID-19—A disease that knows no borders


title: Protein sorting in the Golgi complex

text: Abstract Even after one hundred years, the Golgi apparatus remains a major challenge in the field of Cell Biology. This is particularly true in terms of transport and of protein sorting. For example, the question how cargo proteins are transported through this organelle is still a matter of debate. Emphasis has been put on the role of anterograde and retrograde transport vesicles. These have been proposed to carry cargo from cisterna to cisterna and to recycle components needed for further rounds of transport. Alternatively, anterograde movement of cargo takes place in cisternal membranes rather than transport vesicles. These membranes assemble and mature in a cis to trans direction. In this case, retrograde transport vesicles need to recycle all components of the Golgi apparatus and this demands a highly dynamic and efficient sorting machinery. Here we will discuss possible mechanisms for protein sorting in the context of cisternal maturation and propose that a common mechanism is sufficient to explain both transport of cargo and sorting of resident proteins.


title: Chapter 7 China Infectious Diseases Automated-Alert and Response System (CIDARS)

text: Abstract This chapter introduces the history, design, technical elements, and functional framework of China Infectious Diseases Automated-alert and Response System (CIDARS). The targeted diseases, early warning methods, and response steps are also described. Based on the running data of the system from 2011 to 2013, the performance of CIDARS is analyzed and evaluated, and further direction of CIDARS is also discussed.


title: Flow cytometric detection of alpha‐1‐acid glycoprotein on feline circulating leucocytes

text: To assess whether alpha‐1‐acid glycoprotein (AGP) can be detected on the membrane of feline circulating leucocytes. Design The presence of AGP on circulating leucocytes was investigated in both clinically healthy cats and cats with different diseases. A group of feline coronavirus (FCoV)‐positive cats, comprising cats with feline infectious peritonitis (FIP) and cats not affected by FIP but seropositive for FCoV, were included in this study because the serum concentration of AGP increases during FCoV infection. Procedure Flow cytometry (using an anti‐feline AGP antibody), serum protein electrophoresis, routine haematology and measurement of the serum AGP concentration were performed using blood samples from 32 healthy cats (19 FCoV‐seropositive), 13 cats with FIP and 12 with other diseases (6 FCoV‐seropositive). The proportion of cats with AGP‐positive leucocytes in the different groups (e.g. controls vs sick; FIP vs other diseases, etc.) or in cats with different intensities of inflammatory response was compared using a Chi‐square test. Results AGP‐positive leucocytes were found in 23% of cats. Compared with controls, the proportion of patients with positive granulocytes and monocytes was higher among sick cats (especially cats with diseases other than FIP) and cats with high serum AGP concentration, but not in cats with leucocytosis or that were FCoV‐seropositive. Conclusion AGP‐positive leucocytes can be found in feline blood, especially during inflammation. Conversely, no association between AGP‐positive leucocytes and FIP was found. Further studies are needed to elucidate the mechanism responsible for this finding and its diagnostic role in cats with inflammation.


Recommendations for personal protective equipment and smoke evacuation for dermatologic surgeries amid the COVID‐19 crisis


title: Data-mining to build a knowledge representation store for clinical decision support. Studies on curation and validation based on machine performance in multiple choice medical licensing examinations

text: Abstract Extracting medical knowledge by structured data mining of many medical records and from unstructured data mining of natural language source text on the Internet will become increasingly important for clinical decision support. Output from these sources can be transformed into large numbers of elements of knowledge in a Knowledge Representation Store (KRS), here using the notation and to some extent the algebraic principles of the Q-UEL Web-based universal exchange and inference language described previously, rooted in Dirac notation from quantum mechanics and linguistic theory. In a KRS, semantic structures or statements about the world of interest to medicine are analogous to natural language sentences seen as formed from noun phrases separated by verbs, prepositions and other descriptions of relationships. A convenient method of testing and better curating these elements of knowledge is by having the computer use them to take the test of a multiple choice medical licensing examination. It is a venture which perhaps tells us almost as much about the reasoning of students and examiners as it does about the requirements for Artificial Intelligence as employed in clinical decision making. It emphasizes the role of context and of contextual probabilities as opposed to the more familiar intrinsic probabilities, and of a preliminary form of logic that we call presyllogistic reasoning.


title: Clinical Analysis by Microchip Capillary Electrophoresis

text: Clinical analysis often requires rapid, automated, and high-throughput analytical systems. Microchip capillary electrophoresis (CE) has the potential to achieve very rapid analysis (typically seconds), easy integration of multiple analytical steps, and parallel operation. Although it is currently still in an early stage of development, there are already many reports in the literature describing the applications of microchip CE in clinical analysis. At the same time, more fully automated and higher throughput commercial instruments for microchip CE are becoming available and are expected to further enhance the development of applications of microchip CE in routine clinical testing. To put into perspective its potential, we briefly compare microchip CE with conventional CE and review developments in this technique that may be useful in diagnosis of major diseases.


title: Novel Percutaneous Tracheostomy for Critically Ill Patients with COVID-19

text: Abstract Background COVID-19 is a worldwide pandemic, with many patients requiring prolonged mechanical ventilation. Tracheostomy is not recommended by current guidelines as it is considered a super-spreading event due to aerosolization that unduly risks healthcare workers. Methods Patients with severe COVID-19 that were on mechanical ventilation ≥ 5 days were evaluated for percutaneous dilational tracheostomy. We developed a novel percutaneous tracheostomy technique that placed the bronchoscope alongside the endotracheal tube, not inside it. This improved visualization during the procedure and continued standard mechanical ventilation after positioning the inflated endotracheal tube cuff in the distal trachea. This technique offers a significant mitigation for the risk of virus aerosolization during the procedure. Results From March 10 to April 15, 2020, 270 patients with COVID-19 required invasive mechanical ventilation at New York University Langone Health Manhattan’s campus of which 98 patients underwent percutaneous dilational tracheostomy. The mean time from intubation to the procedure was 10.6 days (SD ±5 days). Currently, thirty-two (33%) patients do not require mechanical ventilatory support, 19 (19%) have their tracheostomy tube downsized and 8 (8%) were decannulated. Forty (41%) patients remain on full ventilator support, while 19 (19%) are weaning from mechanical ventilation. Seven (7%) died as result of respiratory and multiorgan failure. Tracheostomy related bleeding was the most common complication (5 patients). None of health care providers have developed symptoms or tested positive for COVID-19. Conclusions Our percutaneous tracheostomy technique appears to be safe and effective for COVID-19 patients and safe for healthcare workers.


title: The ethics of improving African traditional medical practice: Scientific or African traditional research methods?

text: Abstract The disease burden in Africa, which is relatively very large compared with developed countries, has been attributed to various factors that include poverty, food shortages, inadequate access to health care and unaffordability of Western medicines to the majority of African populations. Although for ‘old diseases’ knowledge about the right African traditional medicines to treat or cure the diseases has been passed from generation to generation, knowledge about traditional medicines to treat newly emerging diseases has to be generated in one way or another. In addition, the existing traditional medicines have to be continuously improved, which is also the case with Western scientific medicines. Whereas one school of thought supports the idea of improving medicines, be they traditional or Western, through scientific research, an opposing school of thought argues that subjecting African traditional medicines to scientific research would be tantamount to some form of colonization and imperialism. This paper argues that continuing to use African traditional medicines for old and new diseases without making concerted efforts to improve their efficacy and safety is unethical since the disease burden affecting Africa may continue to rise in spite of the availability and accessibility of the traditional medicines. Most importantly, the paper commends efforts being made in some African countries to improve African traditional medicine through a combination of different mechanisms that include the controversial approach of scientific research on traditional medicines.


title: Health Inequality as a Large-Scale Outcome of Complex Social Systems: Lessons for Action on the Sustainable Development Goals

text: Action on the Sustainable Development Goals (SDGs) needs to become real and impactful, taking a “whole systems” perspective on levers for systems change. This article reviews what we have learned over the past century about the large-scale outcome of health inequality, and what we know about the behaviour of complex social systems. This combined knowledge provides lessons on the nature of inequality and what effective action on our big goals, like the SDGs, might look like. It argues that economic theories and positivist social theories which have dominated the last 150 years have largely excluded the nature of human connections to each other, and the environment. This exclusion of intimacy has legitimatised arguments that only value-free economic processes matter for macro human systems, and only abstract measurement constitutes valuable social science. Theories of complex systems provide an alternative perspective. One where health inequality is viewed as emergent, and causes are systemic and compounding. Action therefore needs to be intensely local, with power relationships key to transformation. This requires conscious and difficult intervention on the intolerable accumulation of resources; improved reciprocity between social groups; and reversal of system flows, which at present ebb away from the local and those already disadvantaged.


docid: byzuwzje

title: Chapter 3 Microbial Proteomics and Their Importance in Medical Microbiology

text: Abstract Microbial infection is a leading cause of death around the world. Most of the infectious diseases are caused by drug-resistant microbes; this may lead to a delay in the administration of microbiologically effective therapy (Chen et al., 2017; Del Chierico et al., 2014). Therefore, exhaustive understanding of microbial physiologies, infection and defense systems, and survival strategies is of great interest in order to actively defeat microbial infection. Microbial proteomics provides complete information of microbial physiology and expression and function of the proteins that are involved in infection and also gives a clue in clinical diagnosis and antimicrobial therapy (Pérez-Llarena and Bou, 2016; Vranakis et al., 2014). Microbial proteomics helps to identify the proteins associated with microbial activity, microbial host-pathogen interactions, and antimicrobial resistant mechanism. Microbial activity of pathogens can be confirmed by using the 2-D gel-based and gel-free method with the combination of MALDI-TOF-LC-MS/MS. Proteomic analysis of microbial host-pathogen interaction reveals valuable information about the virulence of the pathogen and its resistance; it helps in better understanding of the infection and for developing strategies against microbial infections (Cheng et al., 2016). Fig. 3.1 schematically illustrates the proteomic analysis of the bacterial samples.


title: Chapter 8 The Industry and the Developing World

text: Publisher Summary Effective medicines are hardly available to populations in developing countries; this problem has a series of causes, the responsibility for which lies with different parties. Developing countries are short of money and education, skilled people, and wealthy institutions; many countries also lack adequate communication, the means to exploit what resources they have, and the ability to attract the business and investment that might bring them prosperity. The World Health Organization (WHO) estimates that one-third of the world's population lacks access to the most basic medicines, while in the poorest parts of Africa and Asia this figure climbs to one-half. A pharmaceutical corporation that wishes to meet its obligations to the developing world or to some chosen part of it should ensure the following formal legal obligations: (1) its products meet international standards for quality, efficacy, and safety, (2) the products are accessible, particularly in terms of price, (3) its research programs take account of third-world needs, (4) the information that it provides is adequate and dependable, and (5) its clinical investigations adhere to accepted standards.


Covid‐19 may present with acute abdominal pain


title: Safety of antimicrobial de-escalation for culture-negative severe pneumonia

text: Abstract Purpose This study investigated the outcomes of antimicrobial de-escalation (ADE) based on mortality and the incidence of multi-drug resistant (MDR) pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis and septic shock. Materials and Methods We retrospectively analyzed patients diagnosed with severe pneumonia requiring intensive care unit (ICU) admission and possessing negative microbiological culture results at a tertiary referral hospital in South Korea from March 2008 to July 2018. Results We identified 107 patients with culture-negative pneumonia. The Acute Physiologic and Chronic Health Evaluation (APACHE) II and Sepsis-related Organ Failure Assessment (SOFA) mean scores were 20.3 ± 8.6 and 9.6 ± 3.3, respectively. Among the patients, 40 (37.4%) underwent ADE. The APACHE II, SOFA, and follow-up SOFA scores did not differ significantly between the groups, and no differences were found in ICU mortality and MDR pathogen occurrence (27.5% vs 41.8%, P = .137 and 15.0% vs 16.9% P = .794, respectively). Conclusions We observed similar ICU mortality and MDR pathogen occurrence in patients with culture-negative pneumonia presenting with sepsis/shock regardless of whether they received ADE. Additionally, ADE lowered the antimicrobial burden.


title: The antiviral activity of arbidol hydrochloride against herpes simplex virus type II (HSV-2) in a mouse model of vaginitis

text: Abstract Objective HSV-2 infection has increased significantly in recent years, which is closely associated with cervical cancer and HIV infection. The lack of success in vaccine development and the emergence of drug resistance to commonly used drugs emphasize the urgent need for alternative antivirals against HSV-2 infection. Arbidol (ARB) has been demonstrated to be a broad spectrum antiviral drug that exhibits immunomodulatory properties that affect the HSV-2 life cycle. This study investigated the efficacy and mechanism of ARB against HSV-2 in vivo and in vitro to further explore the clinical application of ARB. Methods The efficacy of ARB on HSV-2 infection in vitro was examined by CPE and MTT assays. A vaginitis model was established to monitor changes in histopathology and inflammatory cytokine (IL-2, IL-4, TNF-α and TGF-β) expression by H&E staining and ELISA, respectively, and the efficacy of ARB was evaluated accordingly. Furthermore, flow cytometry was used to determine the ratio of CD4+/CD8+ T cells in the peripheral blood of the vaginitis animals. Considering the balance of efficacy and pharmacokinetics, ARB ointment was strictly prepared to observe formulation efficacy differences compared to the oral dosing form. Results The results showed that, in vitro, the TC50 and IC50 of ARB were 32.32 μg/mL and 4.77 μg/mL (SI = 6.82), respectively, indicating that ARB presents effective activity against HSV-2 in a dose-dependent manner. The results of the time-course assay suggested that 25 μg/mL ARB affected the late stage of HSV-2 replication. However, ARB did not inhibit viral attachment or cell penetration. The in vivo results showed that ARB ointment can improve the survival rate, prolong the survival time and reduce the reproductive tract injury in mice infected with HSV-2, regulate cytokine expression; and balance the CD4+ and CD8+ T lymphocyte ratio in the peripheral blood to participate in the regulation of immune response. Conclusion ARB showed anti-HSV-2 activity in vitro in a dose-dependent manner and played a role in inhibiting the late replication cycle of the virus. The vaginitis model was successfully established, according to immunomodulation outcomes, responded better to ARB in ointment form than in oral form.


docid: cmcofqec

title: Detection of a novel avian influenza A (H7N9) virus in humans by multiplex one-step real-time RT-PCR assay

text: BACKGROUND: A novel avian influenza A (H7N9) virus emerged in eastern China in February 2013. 413 confirmed human cases, including 157 deaths, have been recorded as of July 31, 2014. METHODS: Clinical specimens, including throat swabs, sputum or tracheal aspirates, etc., were obtained from patients exhibiting influenza-like illness (ILIs), especially from those having pneumonia and a history of occupational exposure to poultry and wild birds. RNA was extracted from these samples and a multiplex one-step real-time RT-PCR assay was developed to specifically detect the influenza A virus (FluA). PCR primers targeted the conserved M and Rnase P (RP) genes, as well as the hemagglutinin and neuraminidase genes of the H7N9 virus. RESULTS: The multiplex assay specifically detected the avian H7N9 virus, and no cross-reaction with other common respiratory pathogens was observed. The detection limit of the assay was approximately 0.05 50% tissue culture infective doses (TCID(50)), or 100 copies per reaction. Positive detection of the H7N9 virus in sputum/tracheal aspirates was higher than in throat swabs during the surveillance of patients with ILIs. Additionally, detection of the matrix (M) and Rnase P genes aided in the determination of the novel avian H7N9 virus and ensured the quality of the clinical samples. CONCLUSIONS: These results demonstrate that the multiplex assay detected the novel avian H7N9 virus with high specificity and sensitivity, which is essential for the early diagnosis and treatment of infected patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2334-14-541) contains supplementary material, which is available to authorized users.


Laboratory findings and clinical approaches in domestic cats with enteropathies


title: Viral evasion of intracellular DNA and RNA sensing

text: The co-evolution of viruses with their hosts has led to the emergence of viral pathogens that are adept at evading or actively suppressing host immunity. Pattern recognition receptors (PRRs) are key components of antiviral immunity that detect conserved molecular features of viral pathogens and initiate signalling that results in the expression of antiviral genes. In this Review, we discuss the strategies that viruses use to escape immune surveillance by key intracellular sensors of viral RNA or DNA, with a focus on RIG-I-like receptors (RLRs), cyclic GMP–AMP synthase (cGAS) and interferon-γ (IFNγ)-inducible protein 16 (IFI16). Such viral strategies include the sequestration or modification of viral nucleic acids, interference with specific post-translational modifications of PRRs or their adaptor proteins, the degradation or cleavage of PRRs or their adaptors, and the sequestration or relocalization of PRRs. An understanding of viral immune-evasion mechanisms at the molecular level may guide the development of vaccines and antivirals.


title: Denplan offers wellbeing support to members during COVID-19 crisis

text: Denplan has introduced support measures to help member dentists and their staff deal with financial, health and personal issues during the COVID-19 crisis During these unprecedented and difficult times, access to health and wellbeing services are of utmost importance


title: The Economic Value of One Health in Relation to the Mitigation of Zoonotic Disease Risks

text: The essence of One Health is an interdisciplinary approach combined with some degree of intersectoral integration that is aimed at mitigation of human and animal health risks, taking account of environmental, ecological, social and economic factors. While a large number of international stakeholders now consider the One Health approach necessary for more effective protection of the global community against health threats, there is still no systematic allocation of resources to integrated national or multinational programmes, partly due to the inertia of existing sectoral systems and the lack of convincing economic arguments in support of the approach. We propose different degrees of sectoral integration depending on system types and associated economic efficiency gains to be expected from a One Health approach. International and regional organisations have an important role in facilitating the adoption of the approach, since the costs and the benefits are often of a regional or even a global nature, such as in the case of avian influenza.


title: Diagnóstico etiológico de las infecciones respiratorias agudas de origen vírico en un hospital pediátrico de Gran Canaria

text: Objetivo Las infecciones respiratorias agudas (IRA) de origen vírico son una causa frecuente de consulta y hospitalización pediátrica. El objetivo de este estudio fue conocer la etiología de dichas infecciones en la isla de Gran Canaria. Métodos Durante 3 años (de mayo de 2002 a mayo de 2005) se recogieron 1957 lavados nasofaríngeos de 1.729 niños atendidos en Urgencias con síntomas compatibles con IRA. En todas las muestras se realizó una técnica rápida de detección de antígeno de virus respiratorio sincitial (VRS) y, en las que se obtuvo resultado negativo, inmunofluorescencia (IF) y cultivo celular (CC). Resultados La mediana de edad fue de 2 meses (intervalo: 0,03-119). Se identificó el agente causal del cuadro respiratorio en 1.032 niños (59,7%). El VRS se detectó en 769 niños (74,5%). Los demás virus identificados, por orden de frecuencia, fueron: virus parainfluenza, rinovirus, adenovirus, virus de la gripe, enterovirus y coronavirus. Se encontraron diferencias estadísticamente significativas al comparar la edad y el tipo de virus detectado: los adenovirus fueron responsables de cuadros en niños de mayor edad (mediana: 6 meses; intervalo: 1-74). Hubo 6 casos de infección mixta. La sensibilidad de la IF en relación con el CC fue del 55,8%, y la especificidad del 99,2%. Conclusiones Los virus respiratorios son responsables de un alto número de casos de IRA, principalmente el VRS. Su identificación es determinante en el tratamiento clínico de los pacientes y en el empleo adecuado de antibacterianos y antivirales. Objective Acute respiratory tract infections (ARTI) of viral origin are a frequent cause of pediatric consultations and hospital admissions. The aim of this study was to investigate the etiology of these infections in Gran Canaria, the Canary Islands, (Spain). Methods From May 2002 through May 2005, 1957 nasopharyngeal washings were collected from 1729 children presenting with ARTI to the Pediatric Emergency Unit. A rapid antigen detection method was performed in every sample to identify respiratory syncytial virus (RSV). An immunofluorescence assay (IFA) and cell culture (CC) was used in RSV-negative samples. Results Median age was 2 months (range, 0.03-119). A viral agent was identified in 1032 children (59.7%). RSV was detected in 769 children (74.5%). Other viruses identified, in order of frequency, were parainfluenza viruses, rhinoviruses, adenoviruses, influenza viruses, enteroviruses, and coronaviruses. Statistical differences were found between age and the type of virus detected: Adenoviruses caused respiratory infections in older children (median age: 6 months; range: 1-74). There were 6 mixed infections. Sensitivity of IFA as compared to CC was 55.8%, and specificity was 99.2%. Conclusions Respiratory viruses are responsible for a large number of ARTI cases in children from Gran Canaria, RSV being the major cause. Viral identification is determinant for managing these patients and making a proper use of antibacterial and antiviral drugs.


title: Safe performance of diagnostic bronchoscopy/EBUS during the SARS‐CoV‐2 pandemic

text: The SARS‐CoV‐2 pandemic is unprecedented in our professional lives and much effort and resources will be devoted to care of patients (and HCW) affected by this illness. We must also continue to aim for the same standard of care for our non‐COVID respiratory patients, while minimizing risks of infection transmission to our colleagues. This commentary addresses the key paired issues of minimizing performance of diagnostic/staging bronchoscopy in patients with suspected/known lung cancer while maximizing the safety of the procedure with respect to HCW transmission of COVID‐19.


title: Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models

text: We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor γ-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.


Nasopharyngeal viral isolates in children with Haemophilusinfluenzae type B meningitis


title: A multi-hazards earth science perspective on the COVID-19 pandemic: the potential for concurrent and cascading crises

text: Meteorological and geophysical hazards will concur and interact with coronavirus disease (COVID-19) impacts in many regions on Earth. These interactions will challenge the resilience of societies and systems. A comparison of plausible COVID-19 epidemic trajectories with multi-hazard time-series curves enables delineation of multi-hazard scenarios for selected countries (United States, China, Australia, Bangladesh) and regions (Texas). In multi-hazard crises, governments and other responding agents may be required to make complex, highly compromised, hierarchical decisions aimed to balance COVID-19 risks and protocols with disaster response and recovery operations. Contemporary socioeconomic changes (e.g. reducing risk mitigation measures, lowering restrictions on human activity to stimulate economic recovery) may alter COVID-19 epidemiological dynamics and increase future risks relating to natural hazards and COVID-19 interactions. For example, the aggregation of evacuees into communal environments and increased demand on medical, economic, and infrastructural capacity associated with natural hazard impacts may increase COVID-19 exposure risks and vulnerabilities. COVID-19 epidemiologic conditions at the time of a natural hazard event might also influence the characteristics of emergency and humanitarian responses (e.g. evacuation and sheltering procedures, resource availability, implementation modalities, and assistance types). A simple epidemic phenomenological model with a concurrent disaster event predicts a greater infection rate following events during the pre-infection rate peak period compared with post-peak events, highlighting the need for enacting COVID-19 counter measures in advance of seasonal increases in natural hazards. Inclusion of natural hazard inputs into COVID-19 epidemiological models could enhance the evidence base for informing contemporary policy across diverse multi-hazard scenarios, defining and addressing gaps in disaster preparedness strategies and resourcing, and implementing a future-planning systems approach into contemporary COVID-19 mitigation strategies. Our recommendations may assist governments and their advisors to develop risk reduction strategies for natural and cascading hazards during the COVID-19 pandemic. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10669-020-09772-1) contains supplementary material, which is available to authorized users.


title: Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities

text: The synthesis of several 6,7,8,9,10,11-hexahydro-9-methyl-5,7:9,11-dimethano-5H-benzocyclononen-7-amines is reported. Several of them display low micromolar NMDA receptor antagonist and/or trypanocidal activities. Two compounds are endowed with micromolar anti vesicular stomatitis virus activity, while only one compound shows micromolar anti-influenza activity. The anti-influenza activity of this compound does not seem to be mediated by blocking of the M2 protein.


title: A spike-modified Middle East respiratory syndrome coronavirus (MERS-CoV) infectious clone elicits mild respiratory disease in infected rhesus macaques

text: The recurrence of new human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) underscores the need for effective therapeutic countermeasures. Nonhuman primate models are considered the gold standard for preclinical evaluation of therapeutic countermeasures. However, MERS-CoV-induced severe respiratory disease in humans is associated with high viral loads in the lower respiratory tract, which may be difficult to achieve in nonhuman primate models. Considering this limitation, we wanted to ascertain the effectiveness of using a MERS-CoV infectious clone (icMERS-0) previously shown to replicate to higher titers than the wild-type EMC 2012 strain. We observed respiratory disease resulting from exposure to the icMERS-0 strain as measured by CT in rhesus monkeys with concomitant detection of virus antigen by immunohistochemistry. Overall, respiratory disease was mild and transient, resolving by day 30 post-infection. Although pulmonary disease was mild, these results demonstrate for the first time the utility of CT imaging to measure disease elicited by a MERS-CoV infectious clone system in nonhuman primate models.


Antiphospholipid antibodies and thrombosis in severe COVID-19 pneumonia: A difficult relationship


title: A Case of Acute Disseminated Encephalomyelitis Associated with Hepatitis C Virus Infection

text: Acute disseminated encephalomyelitis (ADEM) is a monophasic autoimmune demyelinating disease of the central nervous system, which typically follows acute viral or bacterial infection or vaccination. We report a case of ADEM associated with hepatitis C virus (HCV) infection with positive serum and cerebrospinal fluid (CSF) anti-HCV antibody. After steroid treatment, neurologic symptoms were improved. Virus triggers autoimmunity or direct viral invasion plays a part in the genesis of ADEM. This is the first reported case of ADEM with anti-HCV antibody in the CSF.


title: Cholesterol Dependence of Pseudorabies Herpesvirus Entry

text: Lipid rafts are special microdomains in the plasma membrane. They are enriched in sphingolipids and cholesterol, playing critical roles in many biological processes. The purpose of this study is to analyze the requirement of cholesterol, a crucial component of lipid rafts for cell infection by pseudorabies virus (PrV). Cholesterol of plasma membrane or viral envelope was depleted with methyl-beta-cyclodextrin (MβCD), and the infectivity of three strains of PrV was determined with plaque assays. The effect of adding cholesterol to MβCD-treated cells and viruses on cell infection was analyzed. Furthermore, effect of post-adsorption cholesterol depletion on PrV infection was investigated. We show that cholesterol depletion of either the plasma membrane or the viral membrane by MβCD significantly impaired the infectivity of PrV strains Kaplan, Becker, and Bartha K-61. The virus was shown to have lower cholesterol content and to respond to lower MβCD concentrations. Exogenous cholesterol added to either MβCD-treated cells or virions partially restored the virus infectivity. Optimal PrV infection requires cholesterol in viral and plasma membranes.


title: Virus-Specific Regulatory T Cells Ameliorate Encephalitis by Repressing Effector T Cell Functions from Priming to Effector Stages

text: Several studies have demonstrated the presence of pathogen-specific Foxp3(+) CD4 regulatory T cells (Treg) in infected animals, but little is known about where and how these cells affect the effector T cell responses and whether they are more suppressive than bulk Treg populations. We recently showed the presence of both epitope M133-specific Tregs (M133 Treg) and conventional CD4 T cells (M133 Tconv) in the brains of mice with coronavirus-induced encephalitis. Here, we provide new insights into the interactions between pathogenic Tconv and Tregs responding to the same epitope. M133 Tregs inhibited the proliferation but not initial activation of M133 Tconv in draining lymph nodes (DLN). Further, M133 Tregs inhibited migration of M133 Tconv from the DLN. In addition, M133 Tregs diminished microglia activation and decreased the number and function of Tconv in the infected brain. Thus, virus-specific Tregs inhibited pathogenic CD4 T cell responses during priming and effector stages, particularly those recognizing cognate antigen, and decreased mortality and morbidity without affecting virus clearance. These cells are more suppressive than bulk Tregs and provide a targeted approach to ameliorating immunopathological disease in infectious settings.


title: An international perspective on hospitalized patients with viral community-acquired pneumonia

text: Abstract Background Who should be tested for viruses in patients with community acquired pneumonia (CAP), prevalence and risk factors for viral CAP are still debated. We evaluated the frequency of viral testing, virus prevalence, risk factors and treatment coverage with oseltamivir in patients admitted for CAP. Methods Secondary analysis of GLIMP, an international, multicenter, point-prevalence study of hospitalized adults with CAP. Testing frequency, prevalence of viral CAP and treatment with oseltamivir were assessed among patients who underwent a viral swab. Univariate and multivariate analysis was used to evaluate risk factors. Results 553 (14.9%) patients with CAP underwent nasal swab. Viral CAP was diagnosed in 157 (28.4%) patients. Influenza virus was isolated in 80.9% of cases. Testing frequency and viral CAP prevalence were inhomogeneous across the participating centers. Obesity (OR 1.59, 95%CI: 1.01–2.48; p = 0.043) and need for invasive mechanical ventilation (OR 1.62, 95%CI: 1.02–2.56; p = 0.040) were independently associated with viral CAP. Prevalence of empirical treatment with oseltamivir was 5.1%. Conclusion In an international scenario, testing frequency for viruses in CAP is very low. The most common cause of viral CAP is Influenza virus. Obesity and need for invasive ventilation represent independent risk factors for viral CAP. Adherence to recommendations for treatment with oseltamivir is poor.


title: Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: Implication for designing novel mucosal MERS vaccines

text: Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was originally identified in Saudi Arabia in 2012. It has caused MERS outbreaks with high mortality in the Middle East and Europe, raising a serious concern about its pandemic potential. Therefore, development of effective vaccines is crucial for preventing its further spread and future pandemic. Our previous study has shown that subcutaneous (s.c.) vaccination of a recombinant protein containing receptor-binding domain (RBD) of MERS-CoV S fused with Fc of human IgG (RBD-Fc) induced strong systemic neutralizing antibody responses in vaccinated mice. Here, we compared local and systemic immune responses induced by RBD-Fc via intranasal (i.n.) and s.c. immunization pathways. We found that i.n. vaccination of MERS-CoV RBD-Fc induced systemic humoral immune responses comparable to those induced by s.c. vaccination, including neutralizing antibodies, but more robust systemic cellular immune responses and significantly higher local mucosal immune responses in mouse lungs. This study suggests the potential of developing MERS-CoV RBD protein into an effective and safe mucosal candidate vaccine for prevention of respiratory tract infections caused by MERS-CoV.


title: Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers

text: Patients with COVID-19 present a broad spectrum of clinical presentation. Whereas hypoxaemia is the marker of severity, different strategies of management should be customised to five specific individual phenotypes. Many intubated patients present with phenotype 4, characterised by pulmonary hypoxic vasoconstriction, being associated with severe hypoxaemia with “normal” (>40 mL·cmH(2)O(−1)) lung compliance and likely representing pulmonary microvascular thrombosis. Phenotype 5 is often associated with high plasma procalcitonin and has low pulmonary compliance, Which is a result of co-infection or acute lung injury after noninvasive ventilation. Identifying these clinical phenotypes and applying a personalised approach would benefit the optimisation of therapies and improve outcomes.


title: Mesenchymal Stem Cell Infusion Shows Promise for Combating Coronavirus (COVID-19)- Induced Pneumonia

text: A new study published by the journal Aging & Disease reported that intravenous administration of clinical-grade human mesenchymal stem cells (MSCs) into patients with coronavirus disease 2019 (COVID-19) resulted in improved functional outcomes (Leng et al., Aging Dis, 11:216-228, 2020). This study demonstrated that intravenous infusion of MSCs is a safe and effective approach for treating patients with COVID-19 pneumonia, including elderly patients displaying severe pneumonia. COVID-19 is a severe acute respiratory illness caused by a new coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, treating COVID-19 patients, particularly those afflicted with severe pneumonia, is challenging as no specific drugs or vaccines against SARS-CoV-2 are available. Therefore, MSC therapy inhibiting the overactivation of the immune system and promoting endogenous repair by improving the lung microenvironment after the SARS-CoV-2 infection found in this study is striking. Additional studies in a larger cohort of patients are needed to validate this therapeutic intervention further, however.


Intuitive Global Insight Into COVID‐19 Clinical Research Activities—The “COVID‐19 Map of Hope”


title: Non-periodic outbreaks of recurrent epidemics and its network modelling

text: The study of recurrent epidemic outbreaks has been attracting great attention for decades, but its underlying mechanism is still under debate. Based on a large number of real data from different cities, we find that besides the seasonal periodic outbreaks of influenza, there are also non-periodic outbreaks, i.e. non-seasonal or non-annual behaviors. To understand how the non-periodicity shows up, we present a network model of SIRS epidemic with both time-dependent infection rate and a small possibility of persistent epidemic seeds, representing the influences from the larger annual variation of environment and the infection generated spontaneously in nature, respectively. Our numerical simulations reveal that the model can reproduce the non-periodic outbreaks of recurrent epidemics with the main features of real influenza data. Further, we find that the recurrent outbreaks of epidemic depend not only on the infection rate but also on the density of susceptible agents, indicating that they are both the necessary conditions for the recurrent epidemic patterns with non-periodicity. A theoretical analysis based on Markov dynamics is presented to explain the numerical results. This finding may be of significance to the control of recurrent epidemics.


title: COVID‐SAFER: Deprescribing Guidance for Hydroxychloroquine Drug Interactions in Older Adults

text: BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes high morbidity and mortality in older adults with chronic illnesses. Several trials are currently underway evaluating the antimalarial drug hydroxychloroquine as a potential treatment for acute infection. However, polypharmacy predisposes patients to increased risk of drug–drug interactions with hydroxychloroquine and may render many in this population ineligible to participate in trials. OBJECTIVES: We aimed to quantify the degree of polypharmacy and burden of potentially inappropriate medications (PIMs) that older hospitalized adults are taking which would interact with hydroxychloroquine. METHODS: We reanalyzed data from the cohort of patients 65 years and older enrolled in the MedSafer pilot study. We first identified patients taking medications with potentially harmful drug–drug interactions with hydroxychloroquine that might exclude them from participation in a typical coronavirus disease 2019 (COVID‐19) therapeutic trial. Next, we identified medications that were flagged by MedSafer as being potentially inappropriate and crafted guidance around medication management if contemplating the use of hydroxychloroquine. RESULTS: The cohort contained a total of 1,001 unique patients with complete data on their home medications at admission. Of these 1,001 patients, 590 (58.9%) were receiving one or more home medications that could potentially interact with hydroxychloroquine, and of these 255 (43.2%) were flagged as potentially inappropriate by the MedSafer tool. Common classes of PIMs observed were antipsychotics, cardiac medications, and anti‐diabetic agents. CONCLUSION: The COVID‐19 pandemic highlights the importance of medication optimization and deprescribing PIMs in older adults. By acting now to reduce polypharmacy and use of PIMs, we can better prepare this vulnerable population for inclusion in trials and, if substantiated, pharmacologic treatment or prevention of COVID‐19. This article is protected by copyright. All rights reserved.


docid: plulhhav

title: Applying critical systems thinking to social prescribing: a relational model of stakeholder “buy-in”

text: BACKGROUND: Social prescribing (SP) allows health professionals to refer primary care patients toward health and wellbeing interventions and activities in the local community. Now widely implemented across the UK and adopted in other nations, questions arise concerning the modelling of present and future schemes, including challenges to full engagement encountered by stakeholders, which lie beyond the scope of traditional evaluations. Critical Systems Thinking (CST) allows for holistic analysis of fields where multiple stakeholders hold diverse interests and unequal power. METHODS: We use CST to (a) critically examine a developing rural social prescribing scheme from multiple stakeholder perspectives and (b) present a relational model for local social prescribing schemes. Our fieldwork included 24 in-depth interviews, regular planning meetings with key stakeholders, and discussions with those involved with national and international SP landscaping. A modified grounded theory approach was used for the analysis, and to consider the core elements of social prescribing sustainability. RESULTS: Our study confirms that local social prescribing schemes must operate with numerous stakeholder interests in mind, seeking to address real life social complexity and offer integrated solutions to multifaceted issues. Three main areas are discussed: holistic vision and boundary judgments; barriers and facilitators; relational issues and “emotional buy in”. Problems for staff include selecting suitable clients, feedback and technological issues and funding and evaluation pressures. Barriers for clients include health, transport and expense issues, also lack of prior information and GP involvement. Emotional “buy-in” emerged as essential for all stakeholders, but hard to sustain. Based on our findings we propose a positive relational model comprising shared vision, confidence and commitment; motivation and encouragement, support and wellbeing focus, collaborative relationships, communication and feedback, access to information /resources, learning in and from action, with emotional “buy-in” at its heart. CONCLUSION: Those implementing social prescribing in different localities inevitably face hard choices about what and whom to include. Research on the sustainability of social prescribing remains limited, studies are required to ascertain which “holistic” models of social prescribing work best for which communities, who are the main beneficiaries of these approaches and how “buy-in” is best sustained.


title: Frontiers of transcutaneous vaccination systems: Novel technologies and devices for vaccine delivery

text: Abstract Transcutaneous immunization (TCI) systems that use the skin's immune function are promising needle-free, easy-to-use, and low-invasive vaccination alternative to conventional, injectable vaccination methods. To develop effective TCI systems, it is essential to establish fundamental techniques and technologies that deliver antigenic proteins to antigen-presenting cells in the epidermis and dermis while overcoming the barrier function of the stratum corneum. In this review, we provide an outline of recent trends in the development of techniques for the delivery of antigenic proteins and of the technologies used to enhance TCI systems. We also introduce basic and clinical research involving our TCI systems that incorporate several original devices.


title: Pathogen transcriptional profile in nasopharyngeal aspirates of children with acute respiratory tract infection

text: Abstract Background Acute respiratory tract infections (ARI) present a significant morbidity and pose a global health burden. Patients are frequently treated with antibiotics although ARI are most commonly caused by virus, strengthening the need for improved diagnostic methods. Objectives Detect viral and bacterial RNA in nasopharyngeal aspirates (NPA) from children aged 6–23 months with ARI using nCounter. Study design A custom-designed nCounter probeset containing viral and bacterial targets was tested in NPA of ARI patients. Results Initially, spiked control viral RNAs were detectable in ≥6.25ng input RNA, indicating absence of inhibitors in NPA. nCounter applied to a larger NPA sample (n =61) enabled the multiplex detection of different pathogens: RNA viruses Parainfluenza virus (PIV 1–3) and RSV A-B in 21%, Human metapneumovirus (hMPV) in 5%, Bocavirus (BoV), CoV, Influenza virus (IV) A in 3% and, Rhinovirus (RV) in 2% of samples, respectively. RSV A-B was confirmed by Real Time PCR (86.2–96.9% agreement). DNA virus (AV) was detected at RNA level, reflecting viral replication, in 10% of samples. Bacterial transcripts from Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydophila pneumoniae were detected in 77, 69, 26, 8, 3 and 2% of samples, respectively. Conclusion nCounter is robust and sensitive for the simultaneous detection of viral (both RNA and DNA) and bacterial transcripts in NPA with low RNA input (<10ng). This medium-throughput technique will increase our understanding of ARI pathogenesis and may provide an evidence-based approach for the targeted and rational use of antibiotics in pediatric ARI.


title: Comparison of SUMO fusion technology with traditional gene fusion systems: Enhanced expression and solubility with SUMO

text: Despite the availability of numerous gene fusion systems, recombinant protein expression in Escherichia coli remains difficult. Establishing the best fusion partner for difficult-to-express proteins remains empirical. To determine which fusion tags are best suited for difficult-to-express proteins, a comparative analysis of the newly described SUMO fusion system with a variety of commonly used fusion systems was completed. For this study, three model proteins, enhanced green florescent protein (eGFP), matrix metalloprotease-13 (MMP13), and myostatin (growth differentiating factor-8, GDF8), were fused to the C termini of maltose-binding protein (MBP), glutathione S-transferase (GST), thioredoxin (TRX), NUS A, ubiquitin (Ub), and SUMO tags. These constructswere expressed in E. coli and evaluated for expression and solubility. As expected, the fusion tags varied in their ability to produce tractable quantities of soluble eGFP, MMP13, and GDF8. SUMO and NUS A fusions enhanced expression and solubility of recombinant proteins most dramatically. The ease at which SUMO and NUS A fusion tags were removed from their partner proteins was then determined. SUMO fusions are cleaved by the natural SUMO protease, while an AcTEV protease site had to be engineered between NUS A and its partner protein. A kinetic analysis showed that the SUMO and AcTEV proteases had similarK(M) values, but SUMOprotease had a 25-fold higher k(cat) than AcTEV protease, indicating a more catalytically efficient enzyme. Taken together, these results demonstrate that SUMO is superior to commonly used fusion tags in enhancing expression and solubility with the distinction of generating recombinant protein with native sequences.


title: Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs

text: OBJECTIVE: Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies. METHODS: Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases. RESULTS: The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi’s Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24–0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao). CONCLUSIONS: Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at 10.1007/s11655-020-3192-6.


Sedation during the pandemic


title: Épidémiologie microbienne des infections respiratoires basses actualités

text: Résumé La littérature récente n'apporte guère de grandes nouveautés, exposant les résultats d'enquêtes parcellaires utiles, mais qui s'insèrent dans les fourchettes de prévalence déjà connues pour les différentes bactéries. La fréquence des germes retrouvés varie dans le temps et l'espace, mais les trois germes les plus fréquemment en cause dans toutes les séries se recrutent, quel que soit le lieu, parmi les cinq agents que sont Streptococcus pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae et Legionella pneumophila. Ainsi, parmi les pneumopathies documentées, plus de 90 % sont dues à : S. pneumoniae, le plus fréquent chez les malades hospitalisés ; Mycoplasma, Chlamydia et les virus respiratoires, prédominant en ville, avec des variations selon le lieu et l'époque ; Staphylococcus aureus et entérobactéries qui peuvent également être en cause chez le vieillard et les patients atteints de tares majeures ; des associations de germes, avec le pneumocoque notamment, qui sont de plus en plus fréquemment identifiées. Enfin, l'agent causal reste méconnu dans 25 à 50 % des cas. On voit récemment notifier des pneumonies aiguës communautaires à staphylocoques résistants à la méticilline. Le diagnostic virologique (et celui des bactéries liées aux cellules) progresse, grâce à la PCR. Il reste de nombreuses incertitudes sur l'intérêt de ce diagnostic en dehors d'études épidémiologiques, mais aussi sur sa pertinence en pratique clinique. Rien de nouveau pour l'épidémiologie des bronchites aiguës ; pour les exacerbations de bronchopneumopathie chronique obstructive (BPCO), le rôle de H. influenzae, colonisant ou infectant, dans la genèse de l'inflammation bronchique fait toujours l'objet de débats. Abstract The recent literature brings nothing new since it provides only fragmented, though undoubtedly useful, studies which remain within the prevalence interval for the different bacterias. The occurrence of germs varies with time and space; nevertheless, whatever the studied series and the site of the studies, the 3 most frequent causal germs belong to the following five strains: Streptococcus pneumoniae, Influenza A, Mycoplasma pneumoniae, Haemophilus influenzae, and Legionella pneumophila. Thus, 90% of all documented pneumoniae appear to be caused by the following pathogens: Pneumococcus; most frequent in hospitalized patients; Mycoplasma, Chlamydia and respiratory viruses were predominant in outpatients, with great variations; Staphylococcus and enterobacteriace may be encountered, mostly in elderlies with major debilitating diseases; association of germs, generally including pneumococcus, are increasingly identified. Last, in 25% to 50% of cases, the causal agent is not known. Recently, some Staphylococcus meticillin-resistant were identified. The diagnosis of viruses (as well as that of atypical bacterias) seems to have improved, thanks to the use of PCR though the interest of such a diagnosis remains questionable, except for epidemiological studies, as well as the relevance of this type of test in clinical practice. Nothing really new has come out on the epidemiology of acute bronchitis, while in bacterial exacerbation of COPD, attention focused on the colonizing or infective role of H. influenzae in the genesis of bronchus inflammation.


title: Detection and characterization of a novel bat-borne coronavirus in Singapore using multiple molecular approaches

text: Bats are important reservoirs and vectors in the transmission of emerging infectious diseases. Many highly pathogenic viruses such as SARS-CoV and rabies-related lyssaviruses have crossed species barriers to infect humans and other animals. In this study we monitored the major roost sites of bats in Singapore, and performed surveillance for zoonotic pathogens in these bats. Screening of guano samples collected during the survey uncovered a bat coronavirus (Betacoronavirus) in Cynopterus brachyotis, commonly known as the lesser dog-faced fruit bat. Using a capture-enrichment sequencing platform, the full-length genome of the bat CoV was sequenced and found to be closely related to the bat coronavirus HKU9 species found in Leschenault’s rousette discovered in the Guangdong and Yunnan provinces.


title: 6 Acute Lung Injury

text: Abstract A wide variety of insults can produce acute lung damage, inclusive of those that injure the lungs directly. The clinical syndrome of acute onset respiratory distress, dyspnea, and bilateral infiltrates is referred to as acute respiratory distress syndrome. The histologic counterpart of acute respiratory distress syndrome is diffuse alveolar damage, classically characterized by hyaline membranes. Other histologic features of acute lung injury include intraalveolar fibrin, organization, interstitial edema, and reactive pneumocytes. Diffuse alveolar damage and other histologic features of acute lung injury are nonspecific as to etiology, and once identified require the pathologist to search the biopsy for further features that may help identify a specific etiology. This chapter reviews the temporal sequence of acute lung injury and explores the large variety of specific etiologic causes with emphasis on helpful histologic features to identify.


title: The comparative immunology of wild and laboratory mice, Mus musculus domesticus

text: The laboratory mouse is the workhorse of immunology, used as a model of mammalian immune function, but how well immune responses of laboratory mice reflect those of free-living animals is unknown. Here we comprehensively characterize serological, cellular and functional immune parameters of wild mice and compare them with laboratory mice, finding that wild mouse cellular immune systems are, comparatively, in a highly activated (primed) state. Associations between immune parameters and infection suggest that high level pathogen exposure drives this activation. Moreover, wild mice have a population of highly activated myeloid cells not present in laboratory mice. By contrast, in vitro cytokine responses to pathogen-associated ligands are generally lower in cells from wild mice, probably reflecting the importance of maintaining immune homeostasis in the face of intense antigenic challenge in the wild. These data provide a comprehensive basis for validating (or not) laboratory mice as a useful and relevant immunological model system.


title: Susceptibility of Pigs and Chickens to SARS Coronavirus

text: An outbreak of severe acute respiratory syndrome (SARS) in humans, associated with a new coronavirus, was reported in Southeast Asia, Europe, and North America in early 2003. To address speculations that the virus originated in domesticated animals, or that domestic species were susceptible to the virus, we inoculated 6-week-old pigs and chickens intravenously, intranasally, ocularly, and orally with 10(6) PFU of SARS-associated coronavirus (SARS-CoV). Clinical signs did not develop in any animal, nor were gross pathologic changes evident on postmortem examinations. Attempts at virus isolation were unsuccessful; however, viral RNA was detected by reverse transcriptase-polymerase chain reaction in blood of both species during the first week after inoculation, and in chicken organs at 2 weeks after inoculation. Virus-neutralizing antibodies developed in the pigs. Our results indicate that these animals do not play a role as amplifying hosts for SARS-CoV.


title: Telemedicine — maintaining quality during times of transition

text: The COVID-19 crisis has accelerated the adoption of telemedicine, presenting challenges and opportunities for clinicians trying to manage diverse, and not only pandemic-related, health conditions. Here, we consider some limitations of telemedicine and offer a perspective on how clinicians can adapt to working in different health-care delivery systems.


docid: nbosceoz

title: Microfluidic Immunoassays for Sensitive and Simultaneous Detection of IgG/IgM/Antigen of SARS-CoV-2 within 15 min

text: [Image: see text] The outbreak of SARS-CoV-2 is posing serious global public health problems. Facing the emergence of this pandemic, we established a portable microfluidic immunoassay system for easy-to-use, sensitive, rapid (<15 min), multiple, and on-site detection of IgG/IgM/Antigen of SARS-CoV-2 simultaneously. This integrated method was successfully applied for detecting SARS-CoV-2 IgM and IgG antibodies in clinical human serum as well as SARS-CoV-2 antigen in pharyngeal swabs from 26 patients with COVID-19 infection and 28 uninfected people. The assay demonstrated high sensitivity and specificity, which is promising for the diagnosis and monitoring as well as control of SARS-CoV-2 worldwide.


title: 5.20 Analytical Methods in Protein-Templated Dynamic Combinatorial Chemistry

text: Abstract Protein-templated dynamic combinatorial chemistry (DCC) has emerged as a powerful method to identify new inhibitors given that it enables the protein to select its own best binder(s) from a library of interconverting compounds. Since the first report of DCC applied to the discovery of binders for a protein, this elegant tool has been employed on a range of protein targets in early stage of medicinal-chemistry projects. A toolbox with various reversible and biocompatible reactions has become available, and the portfolio of analytical techniques is growing. Despite progress, in most cases, the libraries employed remain of moderate size due to difficulties associated with their analysis. In this article, analytical methods used in protein-templated DCC are described using examples of recent developments and reports.


title: The basic reproduction number and prediction of the epidemic size of the novel coronavirus (COVID-19) in Shahroud, Iran

text: The aim of this study was to estimate the basic reproduction number (R(0)) of COVID-19 in the early stage of the epidemic and predict the expected number of new cases in Shahroud in Northeastern Iran. The R(0) of COVID-19 was estimated using the serial interval distribution and the number of incidence cases. The 30-day probable incidence and cumulative incidence were predicted using the assumption that daily incidence follows a Poisson distribution determined by daily infectiousness. Data analysis was done using ‘earlyR’ and ‘projections’ packages in R software. The maximum-likelihood value of R(0) was 2.7 (95% confidence interval (CI): 2.1−3.4) for the COVID-19 epidemic in the early 14 days and decreased to 1.13 (95% CI 1.03–1.25) by the end of day 42. The expected average number of new cases in Shahroud was 9.0 ± 3.8 cases/day, which means an estimated total of 271 (95% CI: 178–383) new cases for the period between 02 April to 03 May 2020. By day 67 (27 April), the effective reproduction number (R(t)), which had a descending trend and was around 1, reduced to 0.70. Based on the R(t) for the last 21 days (days 46–67 of the epidemic), the prediction for 27 April to 26 May is a mean daily cases of 2.9 ± 2.0 with 87 (48–136) new cases. In order to maintain R below 1, we strongly recommend enforcing and continuing the current preventive measures, restricting travel and providing screening tests for a larger proportion of the population.


title: A Multichannel Real-Time Bioimpedance Measurement Device for Pulse Wave Analysis

text: Pulse wave analysis is an important method used to gather information about the cardiovascular system. Instead of detecting the pulse wave via pressure sensors, bioimpedance measurements can be performed to acquire minuscule changes in the conductivity of the tissue, caused by the pulse wave. This work presents a microcontroller-based bioimpedance measurement system, which has the capability to acquire impedance measurements from up to four independent channels simultaneously. By combining a problem-specific analog measurement circuit with a 24 bits analog-to-digital converter, the system is capable of acquiring 1000 impedances per second with a signal-to-noise ratio in a range from 92 to 96 dB. For data storage and analysis, the digitized data are sent via universal serial bus to a host PC. A graphical user interface filters and plots the data of all channels in real-time. The performance of the system regarding measuring constant impedances, as well as impedance changes over time is demonstrated. Two different applications for pulse wave analysis via multichannel bioimpedance measurements are presented. Additionally, first measurement results from a human subject are shown to demonstrate the system's applicability of analyzing the pulse wave morphology as well as the aortic pulse wave velocity.


title: Pausing cancer screening during the SARS-CoV-2 pandemic: should we revisit the recommendations?

text: • The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China in late 2019, has become a major concern all over the world. • Shortly after the pandemic declaration, medical boards and societies released guidelines stating that medical professionals should use their clinical judgement when scheduling elective surgeries and procedures. • These delays in cancer screening, should not go unnoticed and this “knee-jerk” response should be revisited. • If the current situation last, we anticipate that thousands of cases will be diagnosed late or in some cases will be missed.


title: On the predictability of infectious disease outbreaks

text: Infectious disease outbreaks recapitulate biology: they emerge from the multi-level interaction of hosts, pathogens, and environment. Therefore, outbreak forecasting requires an integrative approach to modeling. While specific components of outbreaks are predictable, it remains unclear whether fundamental limits to outbreak prediction exist. Here, adopting permutation entropy as a model independent measure of predictability, we study the predictability of a diverse collection of outbreaks and identify a fundamental entropy barrier for disease time series forecasting. However, this barrier is often beyond the time scale of single outbreaks, implying prediction is likely to succeed. We show that forecast horizons vary by disease and that both shifting model structures and social network heterogeneity are likely mechanisms for differences in predictability. Our results highlight the importance of embracing dynamic modeling approaches, suggest challenges for performing model selection across long time series, and may relate more broadly to the predictability of complex adaptive systems.


docid: wqpkcikm

title: Envelope–Receptor Interactions in Nipah Virus Pathobiology

text: abstract: Nipah (NiV) and Hendra (HeV) viruses are members of the newly defined Henipavirus genus of the Paramyxoviridae. Nipah virus (NiV) is an emergent paramyxovirus that causes fatal encephalitis in up to 70% of infected patients, and there is increasing evidence of human‐to‐human transmission. NiV is designated a priority pathogen in the NIAID Biodefense Research Agenda, and could be a devastating agent of agrobioterrorism if used against the pig farming industry. Endothelial syncytium is a pathognomonic feature of NiV infections, and is mediated by the fusion (F) and attachment (G) envelope glycoproteins. This review summarizes what is known about the pathophysiology of NiV infections, and documents the identification of the NiV receptor. EphrinB2, the NiV and HeV receptor, is expressed on endothelial cells and neurons, consistent with the known cellular tropism for NiV. We discuss how the identification of the henipahvirus receptor sheds light on the pathobiology of NiV infection, and how it will spur the rational development of effective therapeutics. In addition, ephrinB3, a related protein, can serve as an alternative receptor, and we suggest that differential usage of ephrinB2 versus B3 may explain the variant pathogenic profiles observed between NiV and HeV. Thus, identifying the NiV receptors opens the door for a more comprehensive analysis of the envelope–receptor interactions in NiV pathobiology. Finally, we also describe how galectin‐1 (an innate immune defense lectin) can interact with specific N‐glycans on the Nipah envelope fusion protein, underscoring the potential role that innate immune defense mechanisms may play against emerging pathogens.


title: Ionic liquid-based enzyme-assisted extraction of chlorogenic acid from Flos Lonicera Japonicae

text: BACKGROUND: In recent years, ionic liquids and enzymes have been widely used in the separation and extraction processes of natural products. Chlorogenic acid (CGA) has important biological and pharmacological activities. It is significant to develop a green and efficient method to extract GCA from Flos Lonicera japonica (FLJ) by integrating the advantages of the ionic liquids and enzymes. RESULTS: The optimal type of enzyme and ionic liquid was screened. Pectinase in [C6mim] Br aqueous phase was demonstrated to be an ideal combination. The parameters including extraction time, extraction temperature, pH, enzyme amount, and IL concentration were optimized systematically. Scanning electronic microscopy of FLJ samples demonstrated that pectinase and ionic liquid disposal both obviously facilitated the extraction process by destroying the structure of cell wall. Circular dichroism spectroscopy showed that ionic liquid enhanced the activity of the pectinase by altering its secondary structure. CONCLUSIONS: Compared with previous reported methods, ionic liquid-based enzyme-assisted extraction of GCA from FLJ was proved to be efficient and practical, offering a higher yield in a shorter time. A novel process was proposed for the extraction of active component from natural resources. [Image: see text]