title: Household transmission of SARS-CoV-2

text: Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an epidemic in China and many other countries. Many infected clusters have been found within familial households, but the data about secondary transmission among household contacts is limited. Methods In this retrospective case series, we enrolled 85 patients infected with SARS-CoV-2 and their household members in Wuhan. Patients were confirmed infected with SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) assays on throat swabs. Epidemiological, clinical and laboratory data of the household members were collected. Results There were 155 close contacts in total. 104 contacts received RT-PCR assays, with 47 (30%) positive cases and 57 (37%) negative cases. 51 (33%) cases did not received RT-PCR tests for they showed no symptoms of pneumonia during the 2 weeks of quarantine. The infection rate of close contacts was 38% for households with 1 contact, 50% for households with 2 contacts, and 31% for households with 3 contacts. Conclusions The rate of secondary transmission among household contacts of patients with SARS-CoV-2 infection was 30%. Our data provide insight into the rate of secondary transmission of SARS-CoV-2 in home.


title: Emergence of avian infectious bronchitis in a non-vaccinating country

text: Infectious bronchitis virus (IBV) is a coronavirus of the chicken. It is a highly contagious pathogen and in addition to causing respiratory and kidney diseases can affect the reproductive organs, resulting in loss of production and poor egg quality. Despite the global distribution of IBV, Finland has been free of clinical cases for almost three decades. Since April 2011, outbreaks involving genotypes QX, D274-like and 4/91-like have occurred in southern Finland. The clinical samples studied were submitted to the Finnish Food Safety Authority Evira from different regions of Finland during 2011 to 2013 and originated from a voluntary health monitoring programme, a national survey for avian influenza and diagnostic specimens from both commercial poultry production and hobby flocks. The sources of the infections are not known, but strains D274 and 4/91 are widely used in vaccines elsewhere.


title: Autoprocessing mechanism of severe acute respiratory syndrome coronavirus 3C‐like protease (SARS‐CoV 3CL (pro)) from its polyproteins

text: Like many other RNA viruses, severe acute respiratory syndrome coronavirus (SARS‐CoV) produces polyproteins containing several non‐structural proteins, which are then processed by the viral proteases. These proteases often exist within the polyproteins, and are excised by their own proteolytic activity (‘autoprocessing’). It is important to investigate the autoprocessing mechanism of these proteases from the point of view of anti‐SARS‐CoV drug design. In this paper, we describe a new method for investigating the autoprocessing mechanism of the main protease (M (pro)), which is also called the 3C‐like protease (3CL (pro)). Using our method, we measured the activities, under the same conditions, of the mature form and pro‐forms with the N‐terminal pro‐sequence, the C‐terminal pro‐sequence or both pro‐sequences, toward the pro‐form with both N‐ and C‐terminal pro‐sequences. The data indicate that the pro‐forms of the enzyme have proteolytic activity, and are stimulated by the same proteolytic activity. The stimulation occurs in two steps, with approximately eightfold stimulation by N‐terminal cleavage, approximately fourfold stimulation by C‐terminal cleavage, and 23‐fold stimulation by the cleavage of both termini, compared to the pro‐form with both the N‐ and C‐terminal pro‐sequences. Such cleavage mainly occurs in a trans manner; i.e. the pro‐form dimer cleaves the monomeric form. The stimulation by N‐terminal pro‐sequence removal is due to the cis (intra‐dimer and inter‐protomer) effect of formation of the new N‐terminus, whereas that by C‐terminal cleavage is due to removal of its trans (inter‐dimer) inhibitory effect. A numerical simulation of the maturation pathway is presented.


title: An Invited Commentary on “The Surgeon and the COVID-19 pandemic”

text: • This is an insightful perspective from surgeons working in Italy and the USA on the COVID-19 pandemic and the role of surgeons. • Surgeons have so far been side-lined to supportive roles in this crisis and the focus has been on emergency and intensive care. • Elective surgical activity has been largely cancelled and invasive investigations such as endoscopy have been abandoned. Emergency surgery is occurring as open procedures (rather than laparoscopic) where conservative management is not an option. • Re-establishment of Elective surgery will focus initially on cancer patients that have been delayed. Specialties, countries, and regions will differ in their approach depending on their local infrastructure and resources. • Altered healthcare seeking behaviours have led to a reduction in emergency activity and there may be a rebound surge in demand later on. • Trainees have had their training put on hold, many will inevitably require an extension to their training. • The on-going role of the surgical community in the post COVID-19 era will be a hotly debated topic going forwards. • We thank Roberto Verzaro and Seigo Nishida for their perspective.


title: Expression, purification and characterization of recombinant severe acute respiratory syndrome coronavirus non-structural protein 1

text: The coronavirus (CoV) responsible for severe acute respiratory syndrome (SARS), SARS-CoV, encodes two large polyproteins (pp1a and pp1ab) that are processed by two viral proteases to yield mature non-structural proteins (nsps). Many of these nsps have essential roles in viral replication, but several have no assigned function and possess amino acid sequences that are unique to the CoV family. One such protein is SARS-CoV nsp1, which is processed from the N-terminus of both pp1a and pp1ab. The mature SARS-CoV protein is present in cells several hours post-infection and co-localizes to the viral replication complex, but its function in the viral life cycle remains unknown. Furthermore, nsp1 sequences are highly divergent across the CoV family, and it has been suggested that this is due to nsp1 possessing a function specific to viral interactions with its host cell or acting as a host specific virulence factor. In order to initiate structural and biophysical studies of SARS-CoV nsp1, a recombinant expression system and a purification protocol have been developed, yielding milligram quantities of highly purified SARS-CoV nsp1. The purified protein was characterized using circular dichroism, size exclusion chromatography, and multi-angle light scattering.


title: Unexpected finding of myocardial depression in 2 healthy young patients with COVID‐19 pneumonia: possible support for COVID‐19‐related myocarditis

text: COVID‐19 is proving to be a devastating pandemic with both tragic economic and health consequences worldwide. Point‐of‐care ultrasound (POCUS) of the lungs has been thrust into the forefront of resources that could be used in the management of COVID‐19 acute care patients. However, relatively little attention has been paid to POCUS utility in assessing the heart in COVID‐19 patients. Anecdotal reports suggest encounters of likely COVID‐19 induced pericardial effusions and myocardial electrical dysfunction. This article presents 2 cases of generally healthy patients who were noted to have classic COVID‐19 bilateral pneumonia findings on lung ultrasound and incidentally discovered to have unsuspected left ventricular dysfunction likely resulting from myocarditis. POCUS videos are presented as illustrations of this potentially overlooked complication.


title: Lassa Fever: Viral Replication, Disease Pathogenesis, and Host Immune Modulations

text: Despite major discoveries made in the last few decades about Lassa fever, there are still many unresolved key issues that hamper the development of effective vaccines and therapies against this deadly disease that is endemic in several West African countries. Some of these issues include the lack of a detailed understanding of the viral and participating host factors in completing the virus life cycle, in mediating disease pathogenesis or protection from disease, and in activating or suppressing host innate and cellular immunity against virus infection, as well as of the animal models required for testing vaccines and therapeutics. This Special Issue is devoted to understanding some of these important issues and to exploring the current status of the research and development in combating Lassa fever.


Guidelines for infection prevention and control in perioperative patients during the COVID-19 pandemic: protocol from a tertiary general hospital in Beijing


title: A Review of the Role of Cost–Benefit Analyses in 2-1-1 Diffusion

text: Context The 2-1-1 helpline is a social services innovation that has spread rapidly throughout the U.S. Policy diffusion theory suggests that policymakers seek to reduce uncertainty by anticipating the effects of a proposed innovation through tools such as cost–benefit analyses. Few policy diffusion studies have examined use of information, such as cost–benefit analyses, in the diffusion process. The purpose of this study is to examine how cost–benefit analyses were used during the rapid diffusion of 2-1-1 across states. The paper also describes components of 2-1-1 cost–benefit analyses. Evidence acquisition In 2011, cost–benefit analyses of 2-1-1 and substantive citations of them were identified through scholarly key word searches using Academic Search Premier and Web of Science, general Internet searches using Google search terms, and communications with academicians and 2-1-1 practitioners through personal contact and e-mail discussion groups. To be included in this study, documents had to be related to 2-1-1 helplines, present information about their costs and benefits, and be formal documents. The documents were catalogued and analyzed for cost–benefit analyses or references to analyses, and stated purpose. Evidence synthesis Of the 19 documents that met eligibility inclusion criteria, nine were original cost–benefit analyses and ten referenced analyses conducted for other jurisdictions. Conclusions The diffusion of 2-1-1 helplines in the U.S. has been influenced by interjurisdictional exchange of cost–benefit analyses, in both the creation of original analyses and/or the referencing of previous work.


title: Epidemiology of travel-associated infections in Oman 1999–2013: A retrospective analysis

text: Summary Background The number of travelers in Oman has increased significantly in the last 2 decades with an increase in the expatriate population workforce leading to the emergence of infections related to travel. This paper aims to highlight the burden of travel-related infections in Oman. Method Our study is a descriptive record-based review and analysis of travel-associated diseases over a 14 year time period from 1999 to 2013. The data was sourced from the communicable disease surveillance system, and central public health laboratory results. Results From 1999 to 2013 there were a combined total of 7022 cases of cholera, chikungunya, dengue, filariasis, leptospirosis, meningococcal infection, poliomyelitis, measles, schistosomiasis, viral hepatitis (A), typhoid and para-typhoid reported to and subsequently investigated by the Department of Communicable Diseases. Among these cases, 558 (7.9%) were attributed to travel. Fifty percent of these patients were admitted to hospitals. Conclusion Travel-associated infections account for about 8% of notifiable infections in Oman and have low mortality rate. However, some travel-associated infections are considered as a threat to polio eradication and measles elimination programs. Furthermore, some can cause outbreaks that can overwhelm the healthcare system.


title: Animal virus schemes for translation dominance

text: Viruses have adapted a broad range of unique mechanisms to modulate the cellular translational machinery to ensure viral translation at the expense of cellular protein synthesis. Many of these promote virus-specific translation by use of molecular tags on viral mRNA such as internal ribosome entry sites (IRES) and genome-linked viral proteins (VPg) that bind translation machinery components in unusual ways and promote RNA circularization. This review describes recent advances in understanding some of the mechanisms in which animal virus mRNAs gain an advantage over cellular transcripts, including new structural and biochemical insights into IRES function and novel proteins that function as alternate met-tRNA(i)(met) carriers in translation initiation. Comparisons between animal and plant virus mechanisms that promote translation of viral mRNAs are discussed.


8th Annual Toronto Critical Care Medicine Symposium, 30 October–1 November 2003, Toronto, Ontario, Canada


title: An in-silico evaluation of different Saikosaponins for their potency against SARS-CoV-2 using NSP15 and fusion spike glycoprotein as targets

text: The Public Health Emergency of International Concern declared the widespread outbreak of SARS-CoV-2 as a global pandemic emergency, which has resulted in 1,773,086 confirmed cases including 111,652 human deaths, as on 13 April 2020, as reported to World Health Organization. As of now, there are no vaccines or antiviral drugs declared to be officially useful against the infection. Saikosaponin is a group of oleanane derivatives reported in Chinese medicinal plants and are described for their anti-viral, anti-tumor, anti-inflammatory, anticonvulsant, antinephritis and hepatoprotective activities. They have also been known to have anti-coronaviral property by interfering the early stage of viral replication including absorption and penetration of the virus. Thus, the present study was undertaken to screen and evaluate the potency of different Saikosaponins against different sets of SARS-CoV-2 binding protein via computational molecular docking simulations. Docking was carried out on a Glide module of Schrodinger Maestro 2018-1 MM Share Version on NSP15 (PDB ID: 6W01) and Prefusion 2019-nCoV spike glycoprotein (PDB ID: 6VSB) from SARS-CoV-2. From the binding energy and interaction studies, the Saikosaponins U and V showed the best affinity towards both the proteins suggesting them to be future research molecule as they mark the desire interaction with NSP15, which is responsible for replication of RNA and also with 2019-nCoV spike glycoprotein which manage the connection with ACE2. [Image: see text] Communicated by Ramaswamy H. Sarma


The SARS-Cov-2 pandemic: a good time for stem cell transplantation?


Novel corona virus (COVID‐19) disease and ophthalmic manifestations: Clinical evidences


title: Closure of schools during an influenza pandemic

text: Summary In response to WHO raising the influenza pandemic alert level from phase five to phase six, health officials around the world are carefully reviewing pandemic mitigation protocols. School closure (also called class dismissal in North America) is a non-pharmaceutical intervention that is commonly suggested for mitigating influenza pandemics. Health officials taking the decision to close schools must weigh the potential health benefits of reducing transmission and thus case numbers against high economic and social costs, difficult ethical issues, and the possible disruption of key services such as health care. Also, if schools are expected to close as a deliberate policy option, or just because of high levels of staff absenteeism, it is important to plan to mitigate the negative features of closure. In this context, there is still debate about if, when, and how school closure policy should be used. In this Review, we take a multidisciplinary and holistic perspective and review the multiple aspects of school closure as a public health policy. Implications for the mitigation of the swine-origin influenza A H1N1 pandemic are also discussed.


title: Viruses as vesicular carriers of the viral genome: A functional module perspective

text: Abstract Enveloped viruses and cellular transport vesicles share obvious morphological and functional properties. Both are composed of a closed membrane, which is lined with coat proteins and encases cargo. Transmembrane proteins inserted into the membrane define the target membrane area with which the vesicle or virus is destined to fuse. Here we discuss recent insight into the functioning of enveloped viruses in the framework of the “functional module” concept. Vesicular transport is an exemplary case of a functional module, as defined as a part of the proteome that assembles to perform a specific autonomous function in a living cell. Cellular vesicles serve to transport cargo between membranous organelles inside the cell, while enveloped viruses can be seen as carriers of the viral genome delivering their cargo from an infected to an uninfected cell. The turnover of both vesicles and viruses involves an analogous series of submodular events. This comprises assembly of elements, budding from the donor compartment, uncoating and/or maturation, docking to and finally fusion with the target membrane to release the cargo. This modular perception enables us to define submodular building blocks so that mechanisms and elements can be directly compared. It will be analyzed where viruses have developed their own specific strategy, where they share functional schemes with vesicles, and also where they even have “hijacked” complete submodular schemes from the cell. Such a perspective may also include new and more specific approaches to pharmacological interference with virus function, which could avoid some of the most severe side effects.


title: Targeting Accessories to the Crime: Nanoparticle Nucleic Acid Delivery to the Tumor Microenvironment

text: Nucleic acid delivery for cancer holds extraordinary promise. Increasing expression of tumor suppressor genes or inhibition of oncogenes in cancer cells has important therapeutic potential. However, several barriers impair progress in cancer gene delivery. These include effective delivery to cancer cells and relevant intracellular compartments. Although viral gene delivery can be effective, it has the disadvantages of being immuno-stimulatory, potentially mutagenic and lacking temporal control. Various nanoparticle (NP) platforms have been developed to overcome nucleic acid delivery hurdles, but several challenges still exist. One such challenge has been the accumulation of NPs in non-cancer cells within the tumor microenvironment (TME) as well as the circulation. While uptake by these cancer-associated cells is considered to be an off-target effect in some contexts, several strategies have now emerged to utilize NP-mediated gene delivery to intentionally alter the TME. For example, the similarity of NPs in shape and size to pathogens promotes uptake by antigen presenting cells, which can be used to increase immune stimulation and promote tumor killing by T-lymphocytes. In the era of immunotherapy, boosting the ability of the immune system to eliminate cancer cells has proven to be an exciting new area in cancer nanotechnology. Given the importance of cancer-associated cells in tumor growth and metastasis, targeting these cells in the TME opens up new therapeutic applications for NPs. This review will cover evidence for non-cancer cell accumulation of NPs in animal models and patients, summarize characteristics that promote NP delivery to different cell types, and describe several therapeutic strategies for gene modification within the TME.


title: A stochastic SIRS epidemic model with non-monotone incidence rate under regime-switching

text: Abstract In this paper, we propose and discuss a stochastic SIRS epidemic model with non-monotone incidence rate under regime-switching. First of all, we show that there is a unique positive solution, which is a prerequisite for analyzing the long-term behavior of the stochastic model. Then, a threshold dynamic determined by the basic reproduction number R 0 s is established: the disease can be eradicated almost surely if R 0 s < 1 and under mild extra conditions, whereas if R 0 s > 1 , the densities of the distributions of the solution can converge in L 1 to an invariant density by using the Markov semigroups theory. Finally, based on realistic parameters obtained from previous literatures, numerical simulations have been performed to verify our analytical results.


COVID-19: The Conjunction of Events Leading to the Coronavirus Pandemic and Lessons to Learn for Future Threats


title: Professional autonomy of the resident doctor: Between the hammer and the anvil

text: Abstract Within the regime of professional liability of doctors in training, the limits and the medico-legal aspects of their professional duties are not well-defined. The Italian Court of Cassation established in its sentence no. 26311/2019 that resident doctors do not work at hospitals just to receive their professional training. They are, indeed, licensed physicians and therefore bear full responsibility for the acts performed within the compass of their professional activity. The purpose of this article is to briefly define the possible consequences of this judgment.


title: Universal SARS preventive measures in an obstetrics unit: Experience of health care staff

text: BACKGROUND: Severe acute respiratory syndrome (SARS) epidemics have affected populations in many countries, including Hong Kong. This disease is infectious, especially in hospital settings. Health care workers have expressed great concern, including those working in obstetrics wards, defined as high-risk areas. METHOD: Four weeks after implementation of universal precautionary measures at a teaching hospital in Hong Kong, a survey of the health care staff was conducted to identify their feelings and opinions. RESULTS: In spite of general knowledge about SARS epidemics and related mortality, most respondents stated that universal precautionary measures were not very necessary, especially in the obstetrics ward. In addition, respondents were generally dissatisfied with the measures, as most items imposed extra work, inconvenience, and burdens on the staff. CONCLUSION: Our findings reported the views and satisfaction levels of the front-line staff of an obstetric unit concerning precautionary measures against SARS. The importance of individualized design and implementation of infection control measures is highlighted and discussed.


title: Development of attenuated vaccines from Taiwanese infectious bronchitis virus strains

text: Due to variations in serotypes among different strains of avian infectious bronchitis viruses (IBV), vaccination of chicks with imported vaccines fails to protect them from IBV infections in Taiwan. Therefore, we develop attenuated vaccines from local strains in Taiwan. A Taiwan Group I (TW I) strain was passaged 74 times through specific pathogen-free (SPF) chicken embryonated eggs, and then tested in SPF chickens. The attenuated vaccine was not pathogenic in 1-week-old chicks, had a neutralization index (NI) of greater than 4.4 and efficacy of 90% when inoculated birds were challenged with a field IBV strain. Similar results were obtained for a vaccine made from a Taiwan Group II IBV strain. Additionally, the TW I attenuated vaccine strain had no reversion to virulence after five back passages in chicks. In conclusion, these attenuated vaccines have potential for controlling local Taiwanese IBV infections in chickens.


title: Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020

text: Abstract The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R 0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020.


title: Gender differences in coping and anxiety in patients after coronary artery bypass graft surgery in Taiwan

text: Background Greater use of coping strategies and lower anxiety levels may be related to positive outcomes after coronary artery bypass graft surgery; however, the relationship between them, including by gender, has not been examined in Taiwan. Methods Cross-sectional survey research design and purposive sampling were used in this study, for which 50 men and 50 women were recruited from a medical center in northern Taiwan. Results After coronary artery bypass graft surgery, both male and female patients used more problem-focused coping strategies than emotion-focused coping strategies. In comparison with men, women tended to use more blaming of self and had slightly higher scores on both state and trait anxiety. Conclusion Clinicians need to be aware that the use of appropriate coping strategies can reduce patient anxiety, a finding that needs to be considered when designing effective interventions for these patients.


title: Comparison of recombinant cathepsins L1, L2, and L5 as ELISA targets for serodiagnosis of bovine and ovine fascioliasis

text: Infections caused by Fasciola hepatica are of great importance in the veterinary field, as they cause important economic losses to livestock producers. Serodiagnostic methods, typically ELISA (with either native or recombinant antigens), are often used for early diagnosis. The use of native antigens, as in the MM3-SERO ELISA (commercialized as BIO K 211, BIO-X Diagnostics), continues to be beneficial in terms of sensitivity and specificity; however, there is interest in developing ELISA tests based on recombinant antigens to avoid the need to culture parasites. Of the antigens secreted by adult flukes, recombinant procathepsin L1 (rFhpCL1) is the most commonly tested in ELISA to date. However, although adult flukes produce three different clades of CLs (FhCL1, FhCL2, and FhCL5), to our knowledge, the diagnostic value of recombinant FhCL2 and FhCL5 has not yet been investigated. In the present study, we developed and tested three indirect ELISAs using rFhpCL1, rFhpCL2, and rFhpCL5 and evaluated their recognition by sera from sheep and cattle naturally infected with F. hepatica. Although the overall antibody response to these three rFhpCLs was similar, some animals displayed preferential recognition for particular rFhpCLs. Moreover, for cattle sera, the highest sensitivity was obtained using rFhpCL2 (97%), being equal for both rFhpCL1 and rFhpCL5 (87.9%), after adjusting cut-offs for maximum specificity. By contrast, for sheep sera, the sensitivity was 100% for the three rFhpCLs. Finally, the presence of truncated and/or partially unfolded molecules in antigen preparations is postulated as a possible source of cross-reactivity.


title: Investigation into SARS-CoV-2 Resistance of Compounds in Garlic Essential Oil

text: [Image: see text] Eighteen active substances, including 17 organosulfur compounds found in garlic essential oil (T), were identified by GC–MS analysis. For the first time, using the molecular docking technique, we report the inhibitory effect of the considered compounds on the host receptor angiotensin-converting enzyme 2 (ACE2) protein in the human body that leads to a crucial foundation about coronavirus resistance of individual compounds on the main protease (PDB6LU7) protein of SARS-CoV-2. The results show that the 17 organosulfur compounds, accounting for 99.4% contents of the garlic essential oil, have strong interactions with the amino acids of the ACE2 protein and the main protease PDB6LU7 of SARS-CoV-2. The strongest anticoronavirus activity is expressed in allyl disulfide and allyl trisulfide, which account for the highest content in the garlic essential oil (51.3%). Interestingly, docking results indicate the synergistic interactions of the 17 substances, which exhibit good inhibition of the ACE2 and PDB6LU7 proteins. The results suggest that the garlic essential oil is a valuable natural antivirus source, which contributes to preventing the invasion of coronavirus into the human body.


title: A TLR3 ligand that exhibits potent inhibition of influenza virus replication and has strong adjuvant activity has the potential for dual applications in an influenza pandemic

text: The appearance and spread of the H5N1 highly pathogenic avian influenza (HPAI) raise concern of a possible pandemic. Current preventive measures include the development of a pre-pandemic influenza vaccine and stockpiling of neuraminidase inhibitors. However, their benefits can be significantly reduced by mutations in the hemagglutinin or neuraminidase resulting in antigenic changes and the appearance of drug-resistance, respectively. Drugs that target the innate immune system to achieve a ‘heightened antiviral’ state represent another class of antiviral agents that could contribute to the control and treatment of influenza infection. In this study, PIKA (a stabilized dsRNA) provides broad-spectrum prophylaxis against a number of influenza A viruses. In addition, when PIKA was admixed with influenza vaccine preparations, including a formalin-inactivated whole-virion H5 vaccine, significant adjuvanting effect leading to accelerated viral clearance was observed in a murine model. These biological effects appear to be mediated by the ability of PIKA to promote the maturation of dendritic cells, including up-regulation of co-stimulatory molecules, such as CD80 and CD86, and the induction of various cytokines and chemokines. Toll-like receptor 3 (TLR3) was shown to recognize PIKA in a concentration-dependent manner. The potency and versatility in its activities make PIKA an attractive candidate for use in an influenza pandemic.


title: Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

text: Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.


title: Extrapulmonary and atypical clinical presentations of COVID‐19

text: The novel coronavirus (SARS‐CoV2) has led to outbreak of multiple cases of pneumonia in Wuhan city in December 2019. The disease caused by this virus was named coronavirus disease 2019 or “COVID‐19”, which was declared by WHO as a global pandemic in March 2020. It typically presents with respiratory symptoms and febrile illness. However, there are few reported extrapulmonary and atypical presentations, such as haemoptysis, cardiac, neurological, gastrointestinal, ocular and cutaneous manifestations, as well as venous and arterial thrombosis. Lack of awareness of these presentations might lead to misdiagnosis, delayed diagnosis and isolation of suspected patients which increases the risk of transmission of infection between patients and doctors. All these issues will be discussed in this review. This article is protected by copyright. All rights reserved.


title: Biochemical characterization of a native group III trypsin ZT from Atlantic cod (Gadus morhua)

text: Abstract Atlantic cod trypsin ZT is biochemically characterized for the first time in this report in comparison to a group I trypsin (cod trypsin I). To our knowledge, trypsin ZT is the first thoroughly characterized group III trypsin. A more detailed understanding of trypsin ZT biochemistry may give insight into its physiological role as well as its potential use within the biotechnology sector. Stability is an important factor when it comes to practical applications of enzymes. Compared to trypsin I, trypsin ZT shows differences in pH and heat stability, sensitivity to inhibitors and sub-site substrate specificity as shown by multiplex substrate profiling analysis. Based on the analysis, trypsin ZT cleaved at arginine and lysine as other trypsins. Furthermore, trypsin ZT is better than trypsin I in cleaving peptides containing several consecutive positively charged residues. Lysine- and arginine-rich amino acid sequences are frequently found in human viral proteins. Thus, trypsin ZT may be effective in inactivating human and fish viruses implying a possible role for the enzyme in the natural defence of Atlantic cod. The results from this study can lead to multiple practical applications of trypsin ZT.


title: Overcoming cancer therapeutic bottleneck by drug repurposing

text: Ever present hurdles for the discovery of new drugs for cancer therapy have necessitated the development of the alternative strategy of drug repurposing, the development of old drugs for new therapeutic purposes. This strategy with a cost-effective way offers a rare opportunity for the treatment of human neoplastic disease, facilitating rapid clinical translation. With an increased understanding of the hallmarks of cancer and the development of various data-driven approaches, drug repurposing further promotes the holistic productivity of drug discovery and reasonably focuses on target-defined antineoplastic compounds. The “treasure trove” of non-oncology drugs should not be ignored since they could target not only known but also hitherto unknown vulnerabilities of cancer. Indeed, different from targeted drugs, these old generic drugs, usually used in a multi-target strategy may bring benefit to patients. In this review, aiming to demonstrate the full potential of drug repurposing, we present various promising repurposed non-oncology drugs for clinical cancer management and classify these candidates into their proposed administration for either mono- or drug combination therapy. We also summarize approaches used for drug repurposing and discuss the main barriers to its uptake.


title: Potential benefits of precise corticosteroids therapy for severe 2019-nCoV pneumonia

text: Salvage corticosteroids treatment for critical patients with 2019-nCoV? Corticosteroids are widely used to prevent lung injury caused by severe community-acquired pneumonia (sCAP) due to their excellent pharmacological effects on the suppression of exuberant and dysfunctional systematic inflammation5. Some scholars may not support the corticosteroids treatment for novel coronavirus pneumonia (NCP), because observational studies and systematic reviews have indicated inconclusive clinical evidence on the effect of corticosteroids therapy for viral pneumonias (such as SARS, MERS and H1N1). Additionally, pulse-dose therapy or long-term administration to high dose of corticosteroids in early stage were reported to be possibly harmful6,7,8. However, these conclusions obscured the clinical benefits of corticosteroids on some subgroups of patients, particularly those with severe symptoms, as the clinical effects might be related to the indication (severities of illness), the timing of intervention, the dose and duration of corticosteroids therapy9.


title: Microbial drug discovery: 80 years of progress

text: Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.


title: Using agro-industrial wastes for the cultivation of microalgae and duckweeds: Contamination risks and biomass safety concerns

text: Abstract Aquatic organisms, such as microalgae (Chlorella, Arthrospira (Spirulina), Tetrasselmis, Dunalliela etc.) and duckweed (Lemna spp., Wolffia spp. etc.) are a potential source for the production of protein-rich biomass and for numerous other high-value compounds (fatty acids, pigments, vitamins etc.). Their cultivation using agro-industrial wastes and wastewater (WaW) is of particular interest in the context of a circular economy, not only for recycling valuable nutrients but also for reducing the requirements for fresh water for the production of biomass. Recovery and recycling of nutrients is an unavoidable long-term approach for securing future food and feed production. Agro-industrial WaW are rich in nutrients and have been widely considered as a potential nutrient source for the cultivation of microalgae/duckweed. However, they commonly contain various hazardous contaminants, which could potentially taint the produced biomass, raising various concerns about the safety of their consumption. Herein, an overview of the most important contaminants, including heavy metals and metalloids, pathogens (bacteria, viruses, parasites etc.), and xenobiotics (hormones, antibiotics, parasiticides etc.) is given. It is concluded that pretreatment and processing of WaW is a requisite step for the removal of several contaminants. Among the various technologies, anaerobic digestion (AD) is widely used in practice and offers a technologically mature approach for WaW treatment. During AD, various organic and biological contaminants are significantly removed. Further removal of contaminants could be achieved by post-treatment and processing of digestates (solid/liquid separation, dilution etc.) to further decrease the concentration of contaminants. Moreover, during cultivation an additional removal may occur through various mechanisms, such as precipitation, degradation, and biotransformation. Since many jurisdictions regulate the presence of various contaminants in feed or food setting strict safety monitoring processes, it would be of particular interest to initiate a multi-disciplinary discussion whether agro-industrial WaW ought to be used to cultivate microalgae/duckweed for feed or food production and identify most feasible options for doing this safely. Based on the current body of knowledge it is estimated that AD and post-treatment of WaW can lower significantly the risks associated with heavy metals and pathogens, but it is yet unclear to what extent this is the case for certain persistent xenobiotics.


title: The Surge after the Surge: Cardiac Surgery post-COVID-19

text: ABSTRACT Background The COVID-19 pandemic has dramatically reduced adult cardiac surgery case volumes as institutions and surgeons curtail non-urgent operations. There will be a progressive increase in deferred cases during the pandemic that will require completion within a limited time frame once restrictions ease. We investigated the impact of various levels of increased post-pandemic hospital operating capacity on the time to clear the backlog of deferred cases. Methods We collected data from four cardiac surgery programs across two health systems. We recorded case rates at baseline and during the COVID-19 pandemic. We created a mathematical model to quantify the cumulative surgical backlog based on the projected pandemic duration. We then used our model to predict the time required to clear the backlog depending on the level of increased operating capacity. Results Cardiac surgery volumes fell to 54% of baseline after restrictions were implemented. Assuming a service restoration date of either June 1 or July 1, we calculated the need to perform 216% or 263% of monthly baseline volume, respectively, to clear the backlog in one month. The actual duration required to clear the backlog is highly dependent on hospital capacity in the post-COVID time period, and ranges from one to eight months depending on when services are restored and degree of increased capacity. Conclusions Cardiac surgical operating capacity during the COVID-19 recovery period will have a dramatic impact on the time to clear the deferred cases backlog. Inadequate operating capacity may cause substantial delays and increase morbidity and mortality. If only pre-pandemic capacity is available, the backlog will never clear.


title: Low Lymphocyte Proportion in Bronchoalveolar Lavage Fluid as a Risk Factor Associated with the Change from Trimethoprim/sulfamethoxazole used as First-Line Treatment for Pneumocystis jirovecii Pneumonia

text: BACKGROUND: Trimethoprim/sufamethoxazole (TMP/SMX) is the recommended treatment for Pneumocystis jirovecii pneumonia (PCP). However, the efficacy and the safety of alternative salvage treatments are less guarauteed especially when patient experiences treatment failure and/or an adverse drug reactions (ADR). The purpose of this study is to recognize potential risk factors imitating successful treatment with TMP/SMX among PCP patients. MATERIALS AND METHODS: Ninety one adult patients diagnosed with PCP were included after searching electronical medical records from January 2013 through July 2015 at Asan Medical Center Seoul, Korea. We compared clinical characteristics and laboratory findings including bronchoalveolar lavage (BAL) fluid analysis in patients who experienced TMP/SMX treatment failure or ADR (the case group) versus those who did not (the control group). RESULTS: Among the enrolled PCP patients, 39 (42.9%) required salvage treatment owing to either treatment failure (28, 28.6%) and/or ADR (17, 18.7%). The BAL lymphocyte percentage (25% [IQR, 8–40%] vs. 47% [IQR, 15–62%]; P = 0.005) was lower in the case group. Diabetes mellitus (adjusted odds ratio [aOR] 4.98, 95% confidence interval [95% CI] 1.20–18.58), glomerular filtration rate ≤50 mL/min (aOR 4.48, 95% CI 1.08–18.66), and BAL lymphocyte percentage ≤45% (aOR 9.25, 95% CI 2.47–34.58) were independently associated with the case group in multivariate analysis. CONCLUSION: This study suggests that BAL lymphocyte count may play some role during PCP treatment. Further studies should be followed to reveal what the role of BAL lymphocyte is in the PCP treatment.


title: Advocates for the homeless seeking funding for COVID‐19

text: Now that the federal $8.3 billion appropriations bill has passed and been signed into law this month to stem the spread of the new coronavirus (COVID‐19), advocates are hoping some of that funding reaches one of this country's most vulnerable populations: the homeless.


title: Low-molecular-weight heparin compared with aspirin for the treatment of acute ischaemic stroke in Asian patients with large artery occlusive disease: a randomised study

text: Summary Background Acute stroke patients with large artery occlusive disease (LAOD) have a distinct pathophysiology and may respond differently to anticoagulation treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH), nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD. Methods Acute ischaemic stroke patients with onset of symptoms less than 48 h and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or magnetic resonance angiography) were recruited. Patients were randomly assigned to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0·4 mL twice daily or oral aspirin 160 mg daily for 10 days, and then all received aspirin 80–300 mg once daily for 6 months. This study is registered at www.strokecenter.org/trials (number 493). Findings Among 603 patients recruited, 353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both intracranial and extracranial disease, and 11 had extracranial disease only). The proportion of patients with good outcomes at 6 months (Barthel index ≥85) was 73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%; 95% CI −5 to 13). Analysis of prespecified secondary outcome measures showed a benefit in outcome for LMWH versus aspirin on the modified Rankin scale dichotomised at 0–1 (odds ratio 1·55, 95% CI 1·02–2·35). Haemorrhagic transformation of infarct and severe adverse events were similar in both groups. Post-hoc analyses of patients without LAOD, and all treated patients, showed similar proportions with a good outcome in aspirin and LMWH groups (78% vs 79% and 73% vs 75%, respectively). Interpretation Overall, the results do not support a significant benefit of LMWH over aspirin in patients with LAOD. The benefits indicated in most outcome measures warrant further investigation into the use of anticoagulation for acute stroke in patients with large artery atherosclerosis, particularly in intracranial atherosclerosis.


title: A Model for the Spread of Infectious Diseases in a Region

text: In understanding the dynamics of the spread of an infectious disease, it is important to understand how a town’s place in a network of towns within a region will impact how the disease spreads to that town and from that town. In this article, we take a model for the spread of an infectious disease in a single town and scale it up to simulate a region containing multiple towns. The model is validated by looking at how adding additional towns and commuters influences the outbreak in a single town. We then look at how the centrality of a town within a network influences the outbreak. Our main finding is that the commuters coming into a town have a greater effect on whether an outbreak will spread to a town than the commuters going out. The findings on centrality of a town and how it influences an outbreak could potentially be used to help influence future policy and intervention strategies such as school closure policies.


title: Characterization of expiration air jets and droplet size distributions immediately at the mouth opening

text: Abstract Size distributions of expiratory droplets expelled during coughing and speaking and the velocities of the expiration air jets of healthy volunteers were measured. Droplet size was measured using the interferometric Mie imaging (IMI) technique while the particle image velocimetry (PIV) technique was used for measuring air velocity. These techniques allowed measurements in close proximity to the mouth and avoided air sampling losses. The average expiration air velocity was 11.7m/s for coughing and 3.9m/s for speaking. Under the experimental setting, evaporation and condensation effects had negligible impact on the measured droplet size. The geometric mean diameter of droplets from coughing was 13.5μm and it was 16.0μm for speaking (counting 1–100). The estimated total number of droplets expelled ranged from 947 to 2085 per cough and 112–6720 for speaking. The estimated droplet concentrations for coughing ranged from 2.4 to 5.2cm−3 per cough and 0.004–0.223cm−3 for speaking.


title: Risk for Transportation of Coronavirus Disease from Wuhan to Other Cities in China

text: On January 23, 2020, China quarantined Wuhan to contain coronavirus disease (COVID-19). We estimated the probability of transportation of COVID-19 from Wuhan to 369 other cities in China before the quarantine. Expected COVID-19 risk is >50% in 130 (95% CI 89–190) cities and >99% in the 4 largest metropolitan areas.


title: Viral modulation of stress granules

text: Abstract Following viral infection, the host responds by mounting a robust anti-viral response with the aim of creating an unfavorable environment for viral replication. As a countermeasure, viruses have elaborated mechanisms to subvert the host response in order to maintain viral protein synthesis and production. In the last decade, several reports have shown that viruses modulate the assembly of stress granules (SGs), which are translationally silent ribonucleoproteins (RNPs) and sites of RNA triage. This review discusses recent advances in our understanding of the interactions between viruses and the host response and how virus-induced modulations in SG abundance play fundamental roles in dictating the success of viral replication.


title: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil

text: Abstract The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C. Each 1 °C rise of temperature was associated with a −4.8951% (t = −2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 °C. There is no evidence supporting that the curve declined for temperatures above 25.8 °C. The study had the goal of supporting governance for healthcare policymakers.


title: Effect of a Hospital-based Case Management Approach on Treatment Outcome of Patients with Tuberculosis

text: Background/Purpose Tuberculosis (TB) continues to pose a heavy public health burden in Taiwan. This prospective study analyzed the factors influencing treatment outcome in patients with TB treated with and without a hospital-based case management (HBCM) approach in a referral center in Taipei. Methods A register-based cohort study design was used to enroll all new cases of pulmonary or extra-pulmonary TB from February 2003 to January 2004. The case manager served as the coordinator among patients, physicians and public health nurses, to facilitate compliance with anti-TB treatment. Treatment outcomes were assessed according to the consensus recommendations of the World Health Organization and the International Union Against Tuberculosis and Lung Disease. Results Suspected or confirmed pulmonary or extrapulmonary TB was diagnosed in 524 patients in our hospital from February 2003 to January 2004. Fifty-two of these patients were excluded due to duplicate reporting, previous treatment or death before enrollment. Out of 472 patients enrolled, 103 whose original diagnosis was revised were further excluded, leaving 369 cases eligible for analysis. Patients with case management had a significantly higher rate of successful treatment (cured plus completed treatment) compared to patients without case management, (240/277, 86.6% vs. 67/92, 72.8%; p = 0.002). The overall successful treatment rate including both case and non-case management was 83.2% (307/369), which was higher than the nationwide surveillance data of 78.3% in 2002 and 69.4% in 2003. Conclusion Treatment of TB patients by a HBCM approach provides improved treatment outcomes compared to those without case management.


title: The emotional impact of Coronavirus 2019-nCoV (new Coronavirus disease)

text: Abstract Background : A novel form of Coronavirus (2019-nCoV) in Wuhan has created a confused and rapidly evolving situation. In this situational framework, patients and front-line healthcare workers are vulnerable. Method : Studies were identified using large-circulation international journals found in two electronic databases: Scopus and Embase. Results : Populations of patients that may require tailored interventions are older adults and international migrant workers. Older adults with psychiatric conditions may be experiencing further distress. The COVID-19 epidemic has underscored potential gaps in mental health services during emergencies. Conclusions : Most health professionals working in isolation units and hospitals do not receive any training for providing mental health care. Fear seems more certainly a consequence of mass quarantine.


title: Evaluating the 3C-like protease activity of SARS-Coronavirus: Recommendations for Standardized Assays for Drug Discovery

text: Although the initial outbreaks of the deadly coronavirus that causes severe acute respiratory syndrome (SARS-CoV) were controlled by public health measures, the development of vaccines and antiviral agents for SARS-CoV is essential for improving control and treatment of future outbreaks. One potential target for SARS-CoV antiviral drug development is the 3C-like protease (3CLpro). This enzyme is an attractive target since it is essential for viral replication, and since there are now a number of high resolution x-ray structures of SARS-CoV 3CLpro available making structure-based drug-design possible. As a result, SARS-CoV 3CLpro has become the focus of numerous drug discovery efforts worldwide, but as a consequence, a variety of different 3CLpro expression constructs and kinetic assays have been independently developed making evaluation and comparison between potential inhibitors problematic. Here, we review the literature focusing on different SARS-CoV 3CLpro expression constructs and assays used to measure enzymatic activity. Moreover, we provide experimental evidence showing that the activity of 3CLpro enzymatic is significantly reduced when non-native sequences or affinity-tags are added to the N- or C-termini of the enzyme, or when the enzyme used in assays is at concentrations below the equilibrium dissociation constant of the 3CLpro dimer. We demonstrate for the first time the utility of a highly sensitive and novel Alexa488-QSY7 FRET-based peptide substrate designed for routine analysis and high-throughput screening, and show that kinetic constants determined from FRET-based assays that are uncorrected for inner-filter effects can lead to artifacts. Finally, we evaluated the effects of common assay components including DTT, NaCl, EDTA and DMSO on enzymatic activity, and we recommend standardized assay conditions and constructs for routine SARS-CoV 3CLpro assays to facilitate direct comparisons between SARS-CoV 3CLpro inhibitors under development worldwide.


title: Bronchoalveolar lavage cytokines are of minor value to diagnose complications following lung transplantation

text: Abstract Early diagnosis and treatment of acute cellular rejection (ACR) may improve long-term outcome for lung transplant recipients (LTRs). Cytokines have become valuable diagnostic tools in many medical fields. The role of bronchoalveolar lavage (BAL) cytokines is of unknown value to diagnose ACR and distinguish rejection from infection. We hypothesized that distinct cytokine patterns obtained by surveillance bronchoscopies during the first year after transplantation are associated with ACR and microbiologic findings. We retrospectively analyzed data from 319 patients undergoing lung transplantation at University Hospital Zurich from 1998 to 2016. We compared levels of IL-6, IL-8, IFN-γ and TNF-α in 747 BAL samples with transbronchial biopsies (TBB) and microbiologic results from surveillance bronchoscopies. We aimed to define reference values that would allow distinction between four specific groups “ACR”, “infection”, “combined ACR and infection” and “no pathologic process”. No definitive pattern was identified. Given the overlap between groups, these four cytokines are not suitable diagnostic markers for ACR or infection after lung transplantation.


Role of Regional Anaesthesia in Laparoscopy During COVID-19


docid: pjwgrejn

title: Increased expression of CD8 marker on T-cells in COVID-19 patients

text: Abstract Background Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients. Methods Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry. Results The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05). Conclusion Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.


title: Overview of COVID‐19 testing and implications for otolaryngologists

text: BACKGROUND: Testing for SARS‐CoV‐2 is important for decision making prior to surgery in otolaryngology. An understanding of current and developing testing methods is important for interpreting test results. METHODS: We performed a literature review of current evidence surrounding SARS‐CoV‐2 diagnostic testing highlighting its utility, limitations, and implications for otolaryngologists. RESULTS: The currently accepted RT‐PCR test for SARS‐CoV‐2 has varying sensitivity according to which subsite of the aerodigestive tract is sampled. Nasal swab sensitivities appear to be about 70%. Chest CT imaging for screening purposes is not currently recommended. CONCLUSION: Due to the current sensitivity of RT‐PCR based testing for SARS‐CoV‐2, a negative test cannot rule out COVID‐19. Full PPE should be worn during high‐risk procedures such as aerosol generating procedures even if testing is negative. Patients who test positive during screening should have their surgeries postponed if possible until asymptomatic and have tested negative for SARS‐CoV‐2.


title: Chapter Five Modified Vaccinia Virus Ankara History, Value in Basic Research, and Current Perspectives for Vaccine Development

text: Abstract Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology.


title: Novel canine circovirus strains from Thailand: Evidence for genetic recombination

text: Canine circoviruses (CanineCV’s), belonging to the genus Circovirus of the Circoviridae family, were detected by next generation sequencing in samples from Thai dogs with respiratory symptoms. Genetic characterization and phylogenetic analysis of nearly complete CanineCV genomes suggested that natural recombination had occurred among different lineages of CanineCV’s. Similarity plot and bootscaning analyses indicated that American and Chinese viruses had served as major and minor parental viruses, respectively. Positions of recombination breakpoints were estimated using maximum-likelihood frameworks with statistical significant testing. The putative recombination event was located in the Replicase gene, intersecting with open reading frame-3. Analysis of nucleotide changes confirmed the origin of the recombination event. This is the first description of naturally occurring recombinant CanineCV’s that have resulted in the circulation of newly emerging CanineCV lineages.


title: Spatiotemporal Patterns and Diffusion of the 1918 Influenza Pandemic in British India

text: The factors that drive spatial heterogeneity and diffusion of pandemic influenza remain debated. We characterized the spatiotemporal mortality patterns of the 1918 influenza pandemic in British India and studied the role of demographic factors, environmental variables, and mobility processes on the observed patterns of spread. Fever-related and all-cause excess mortality data across 206 districts in India from January 1916 to December 1920 were analyzed while controlling for variation in seasonality particular to India. Aspects of the 1918 autumn wave in India matched signature features of influenza pandemics, with high disease burden among young adults, (moderate) spatial heterogeneity in burden, and highly synchronized outbreaks across the country deviating from annual seasonality. Importantly, we found population density and rainfall explained the spatial variation in excess mortality, and long-distance travel via railroad was predictive of the observed spatial diffusion of disease. A spatiotemporal analysis of mortality patterns during the 1918 influenza pandemic in India was integrated in this study with data on underlying factors and processes to reveal transmission mechanisms in a large, intensely connected setting with significant climatic variability. The characterization of such heterogeneity during historical pandemics is crucial to prepare for future pandemics.


title: Control of Severe Acute Respiratory Syndrome in Singapore

text: A Severe Acute Respiratory Syndrome (SARS) outbreak occurred in Singapore from February to May 2003. A high vigilance for the disease, frequent and regular temperature monitoring, early case identification and isolation of patients, as well as tracing and home quarantine of contacts, played major roles in controlling the outbreak. Hospitals were dedicated to the screening and treatment of SARS patients. Within and between hospitals, movement by healthcare workers, patients and visitors were restricted, as was the number of hospital visitors. Staff education and audits of infection control practices also featured prominently. To prevent cross-border transmission, incoming travellers from SARS affected areas had to complete health declaration cards. They, as well as all outgoing travellers from Singapore, were monitored for fever. In the meantime, the public was urged to refrain from travelling to SARS affected regions. Containment elements targeting the community included school closure, public education on good hygiene and readily accessible public information. In response to a laboratory acquired SARS infection, laboratories were audited, and directives issued on the mandatory use of biosafety level 3 laboratories for SARS virus culture, and compliance of laboratory workers to biosafety guidelines.


title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction

text: Ebola virus (EBOV) infection is a widespread infection that has created a bad memory in Africa. In the 2014 and 2015 outbreak, more than 28,000 infections were reported by the World Health Organization, with about 11,300 deaths in Guinea, Liberia, and Sierra Leone. Heat shock protein A5 (HSPA5), termed also GRP78, is a host cell chaperone protein responsible for the unfolded protein response in the endoplasmic reticulum. Under stress, HSPA5 is upregulated and becomes cell-surface exposed. Recent studies report the association of cell-surface HSPA5 with EBOV glycoproteins GP1 and GP2. In this study, structural and sequence analysis and molecular docking are used to predict the possible binding site between the cell-surface HSPA5 and EBOV GP1. The results show a promising binding site that supports the hypothesis of HSPA5 selectivity for binding to a specific peptide sequence (pep42). This study paves the way to suggest possible inhibitors to stop viral association with cell-surface receptors and subsequently reduce viral infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12192-020-01106-z) contains supplementary material, which is available to authorized users.


docid: eawmuuye

title: Computer network for a diagnostic virology laboratory

text: Abstract A data base for a large diagnostic virology laboratory is described. The system uses a network of personal computers. It allows the entry, long-term storage, and subsequent retrieval of specimen and patient records (comprising personal identifiers and specimen and result information), and hard-copy results reporting. Sited entirely within the laboratory, the network is not connected to a modem. Within the laboratory there is restricted access to human immunodeficiency virus test results to guarantee patient confidentiality. Retention of a hard-copy of specimen request cards ensures the availability of the original clinical information. The data base is copied on a second file server to facilitate searches, and daily streaming onto magnetic tape provides system protection in the event of hard disc failure. Matching of old and new patient records is done by surname, date of birth, and sex, and therefore duplicate records accumulate when patient names are misspelt on specimen request forms. The system requires further development to speed searches of the data base and to achieve automatic generation of laboratory worksheets. Future goals are the replacement of hard-copy records of clinical information and hard-copy reporting with on-line access to hospital data bases and on-line requesting by and reporting to the clinician.


title: Epidemiology and Transmission of Respiratory Infections in Thai Army Recruits: A Prospective Cohort Study

text: Military recruits are at high risk of respiratory infections. However, limited data exist on military populations in tropical settings, where the epidemiology of respiratory infections differs substantially from temperate settings. We enrolled recruits undertaking a 10-week military training at two Royal Thai Army barracks between May 2014 and July 2015. We used a multiplex respiratory panel to analyze nose and throat swabs collected at the start and end of the training period, and from participants experiencing respiratory symptoms during follow-up. Paired sera were tested for influenza seroconversion using a hemagglutinin inhibition assay. Overall rates of upper respiratory illness and influenza-like illness were 3.1 and 2.0 episodes per 100 person-weeks, respectively. A pathogen was detected in 96% of samples. The most commonly detected microbes were Haemophilus influenzae type B (62.7%) or non–type B (58.2%) and rhinovirus (22.4%). At baseline, bacterial colonization was high and included H. influenzae type B (82.3%), H. influenzae non–type B (31.5%), Klebsiella pneumoniae (14.6%), Staphylococcus aureus (8.5%), and Streptococcus pneumoniae (8.5%). At the end of follow-up, colonization with H. influenzae non–type B had increased to 74.1%, and S. pneumoniae to 33.6%. In the serology subset, the rate of influenza infection was 3.4 per 100 person-months; 58% of influenza infections resulted in clinical disease. Our study provides key data on the epidemiology and transmission of respiratory pathogens in tropical settings. Our results emphasize the need for improved infection prevention and control in military environments, given the high burden of illness and potential for intense transmission of respiratory pathogens.


title: Pandemic influenza preparedness: The critical role of the syringe

text: In the face of an almost unprecedented threat of a global pandemic of influenza it is imperative that stockpiling of appropriate drugs and devices begin now. One vital device is an appropriate syringe for delivering vaccine. With the potential for millions to be infected and the vaccine supply severely stretched it is imperative that the syringe used to vaccinate waste as little vaccine as possible and thus allow for a maximum number of persons to be vaccinated. Our study tested seven leading candidate vaccine syringes for dosing accuracy, dose-capacity per vial, medication wastage and a battery of ergonomic features. One device, the Flu+™ syringe, proved superior to the others in all important categories, possibly due to its low dead-space volume and its dosing accuracy. The data suggest that switching to this device from any of the others tested would provide between 2 and 19% additional vaccine doses per vial if the current 10-dose vials are used. Extrapolations from this data suggest that many thousands to millions of additional persons could be vaccinated in mass campaigns. Use of a syringe of this type, and the vaccine savings that would accrue, would likely be important in reducing morbidity and mortality in the event of a pandemic of influenza.


title: Rapid and real-time detection of Porcine Sapelovirus by reverse transcription loop-mediated isothermal amplification assay

text: Abstract The present study describes the development and validation of a one-step, single-tube, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) detecting Porcine Sapelovirus. RT-LAMP characterized by one strand displacement reaction with the specific stem-loop structure and Bst DNA polymerase could be finished in 60min under isothermal condition at 63°C. RT-LAMP assay showed higher sensitivity with 101 copies/μL than RT-PCR for the detection of Sapelovirus. The specificity of RT-LAMP assay was validated by the absence of any cross-reaction with other closely related virus in Picornaviridae group and other common virus causing porcine diarrhea. 7 positive Sapelovirus infection out of 63 fecal samples were identified using RT-LAMP, while 5 positive samples were determined by a conventional RT-PCR. A cost-effective method for Saplovirus detection with high sensitivity and specificity was developed and evaluated.


title: Interferon lambda inhibits dengue virus replication in epithelial cells

text: BACKGROUND: In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. METHODS: Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. RESULTS: We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG’s peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. CONCLUSIONS: Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.


title: Telemedicine as a tool for PrEP delivery during the COVID-19 Pandemic in a large HIV Prevention service in Rio de Janeiro-Brazil

text: Abstract COVID-19 public health responses such as social distancing and community containment measures protocols are critical to preventing and containing the spread of coronavirus. Brazil accounts for almost half of Latin American HIV cases and Rio de Janeiro is the city with the second largest number of AIDS. Clinical appointments and pharmacy antiretroviral refills may be impaired due to restricted traffic and possible lockdowns, preventing people living with HIV and those using PrEP from accessing needed antiretrovirals. We hereby describe the telemedicine procedures implemented in a large PrEP delivery in Rio de janeiro in the context of the COVID-19 pandemic. At the initial teleconsultation, individuals undergoe HIV rapid testing and are assessed by phone for PrEP related procedures. Individuals receive a digital prescription to retrieve a 120-day PrEP supply plus two HIV self-test kits. Subsequent follow-up teleconsultations will be performed remotely by phone call, including instructions for the HIV self-test performance, which results are to be sent using a digital picture. Participants will attend the service only for PrEP refill. The use of telemedicine procedures is being effective to avoid PrEP shortage and reduce the time PrEP users spend at the service during the COVID-19 pandemic and social distancing recommendations.


title: Detection of bocavirus DNA in nasopharyngeal aspirates of a child with bronchiolitis

text: Summary We describe a case of bronchiolitis associated with the newly detected human bocavirus (hBoV) in a child with a suspected Noonan syndrome. This is the first report of a bronchiolitis probably linked to hBoV that required intensive care while being accompanied by a congenital heart disease and a history of several episodes of severe respiratory symptoms.


title: Dual activity of niclosamide to suppress replication of integrated HIV-1 and Mycobacterium tuberculosis (Beijing)

text: Abstract The human immunodeficiency virus (HIV) pandemic is driving the re-emergence of tuberculosis (TB) as a global health threat, both by increasing the susceptibility of HIV-infected people to infection with Mycobacterium tuberculosis (Mtb), and increasing the rate of emergence of drug-resistant Mtb. There are several other clinical challenges for treatment of co-infected patients including: expense, pill burden, toxicity, and malabsorption that further necessitate the search for new drugs that may be effective against both pathogens simultaneously. The anti-helminthic niclosamide has been shown to have activity against a laboratory strain of Mtb in liquid culture while bacteriostatic activity against non-replicating M. abscessus was also recently described. Here we extend these findings to further demonstrate that niclosamide inhibits mycobacterial growth in infected human macrophages and mediates potent bacteriostatic activity against the virulent Mtb Beijing strain. Importantly, we provide the first evidence that niclosamide inhibits HIV replication in human macrophages and Jurkat T cells through post-integration effects on pro-virus transcription. The dual antiviral and anti-mycobacterial activity was further observed in an in vitro model of HIV and Mtb co-infection using human primary monocyte-derived macrophages. These results support further investigation of niclosamide and derivatives as anti-retroviral/anti-mycobacterial agents that may reduce clinical challenges associated with multi-drug regimens and drug resistance.


title: The TLR4 Agonist Immunomax Affects the Phenotype of Mouse Lung Macrophages during Respiratory Syncytial Virus Infection

text: In the study, the effect of the TLR4 agonist Immunomax was investigated in vitro and in vivo. In particular, Immunomax was shown to polarize mouse bone marrow macrophages from the M0 and M2 states into the M1 state (ARG1 and iNOS mRNA expression levels were used to identify the mouse M1 and M2 phenotypes). Next, we investigated the prophylactic antiviral effect of Immunomax in both a model of mouse respiratory syncytial virus (RSV) infection and a model of RSV-induced bronchial asthma (BA) exacerbation. In the experiment with RSV-induced BA exacerbation, Immunomax-treated mice were characterized by a significant decrease of the viral load in lung homogenates, an increased amount of M1 macrophages in the lung, a tendency toward Th2-dependent ovalbumin-specific IgG1 antibodies decrease in blood serum, a significant increase in RSV-activated CD4+ T cells secreting IFNγ (Th1 cells), and a simultaneous significant decrease in the amount of CD4(+) cells secreting IL-4 (Th2 cells) in the mouse spleen, which were detected by ELISPOT 1.5 months after experiment. These findings suggest that treatment with the TLR4 agonist Immunomax polarizes the immune response towards antiviral Th1 and may be used for short-term antiviral prophylaxis to prevent acute respiratory viral infections in asthmatics.


title: COVID‐19 in a melanoma patient under treatment with checkpoint‐inhibition

text: SARS‐CoV‐2 poses new challenges in all aspects of healthcare. Patients with preexisting cardio‐vascular conditions are at higher risk of developing severe symptoms and worse outcome. Data also suggest that cancer patients are particularly vulnerable, but differences between tumor entities and cancer treatments may exist. Little is known how cancer treatment engaging immune checkpoints affects the course of COVID‐19.


title: Protein microarrays for systems biology

text: Systems biology holds the key for understanding biological systems on a system level. It eventually holds the key for the treatment and cure of complex diseases such as cancer, diabetes, obesity, mental disorders, and many others. The ‘-omics' technologies, such as genomics, transcriptomics, proteomics, and metabonomics, are among the major driving forces of systems biology. Featured as high-throughput, miniaturized, and capable of parallel analysis, protein microarrays have already become an important technology platform for systems biology. In this review, we will focus on the system level or global analysis of biological systems using protein microarrays. Four major types of protein microarrays will be discussed: proteome microarrays, antibody microarrays, reverse-phase protein arrays, and lectin microarrays. We will also discuss the challenges and future directions of protein microarray technologies and their applications for systems biology. We strongly believe that protein microarrays will soon become an indispensable and invaluable tool for systems biology.


title: H5N1 infection causes rapid mortality and high cytokine levels in chickens compared to ducks

text: Abstract Infection with H5N1 influenza virus is often fatal to poultry with death occurring in hours rather than days. However, whilst chickens may be acutely susceptible, ducks appear to be asymptomatic to H5N1. The mechanisms of disease pathogenesis are not well understood and the variation between different species requires investigation to help explain these species differences. Here we investigated the expression of several key proinflammatory cytokines of chickens and ducks following infection with 2 highly pathogenic H5N1 (A/Muscovy duck/Vietnam/453/2004 (Vt453) and A/Duck/Indramayu/BBVW/109/2006 (Ind109)) and a low-pathogenic H5N3 influenza virus (A/Duck/Victoria/1462/2008 (Vc1462)). H5N1 viruses caused fatal infections in chickens as well as high viral loads and increased production of proinflammatory molecules when compared to ducks. Cytokines, including Interleukin 6 (IL6) and the acute phase protein Serum Amyloid A (SAA), were rapidly induced at 24h post infection with H5N1. In contrast, low induction of these cytokines appeared in ducks and only at later times during the infection period. These observations support that hypercytokinemia may contribute to pathogenesis in chickens, whilst the lower cytokine response in ducks may be a factor in their apparent resistance to disease and decreased mortality.


docid: tgszveav

title: Dorsal root ganglia may be reservoirs of viral infection in multiple sclerosis

text: Abstract There are presently two competitive theories that attempt to explain the etiology of multiple sclerosis (MS). Briefly summarized, they are: 1. An infection, probably of viral type, may attack the oligodendroglia of the central nervous system; or, 2. An autoimmune process may begin with an infection of the peripheral lymphatic immune system, producing antibodies that cross the blood-brain barrier, leading to myelinoclasia. Since 1935, research has been directed toward myelin of the central nervous system and the myelin sheaths of peripheral nerve; however, dorsal root and cranial sensory ganglia (DRG) have apparently not been studied. The present hypothesis states that an infectious agent (probably viral) finds privileged sanctuary in the dorsal root and cranial sensory ganglia (DRG): thereafter periodically invading the spinal cord, brain, or peripheral nerve. Previously reported erratic spinal fluid viral titers and cultures can be explained by differences in the anatomy of the DRG in which there is a variable and limited contact of spinal fluid with sensory ganglia. Clues to this hypothesis were noted by the author during routine neurological examinations of patients with MS, in which sensory signs and symptoms were frequently encountered. This clinical observation has also been reported by others who found such symptoms in 75% of MS patients, ranking second only to incoordination.


title: Position Paper on Road Map for RNA Virus Research in India

text: The Indian subcontinent with its population density, climatic conditions, means of subsistence, socioeconomic factors as well as travel and tourism presents a fertile ground for thriving of RNA viruses. Despite being pathogens of huge significance, there is very little focus on research into the biology and pathogenesis of RNA viruses in India. Studies on epidemiology and disease burden, risk factors, the immune response to RNA viruses, circulating virus strains and virus evolution, animal models of disease, antivirals and vaccines are strikingly absent. Emerging RNA viruses such as Zika virus, Nipah virus and Crimean-Congo haemorrhagic fever virus are a matter of grave concern to India. Here we summarize the outcome of the India|EMBO symposium on “RNA viruses: immunology, pathogenesis and translational opportunities” organized at Faridabad, National Capital Region, India, on March 28–30, 2018. The meeting focused on RNA viruses (non-HIV), and both national and international experts on RNA viruses covered topics ranging from epidemiology, immune response, virus evolution and vaccine trials concerning RNA viruses. The aim of the symposium was to create a road map for RNA virus research in India. Both concrete and tentative ideas pointing towards short-term and long-term goals were presented with recommendations for follow-up at government level.


title: Critical care and the global burden of critical illness in adults

text: Summary Critical care has evolved from treatment of poliomyelitis victims with respiratory failure in an intensive care unit to treatment of severely ill patients irrespective of location or specific technology. Population-based studies in the developed world suggest that the burden of critical illness is higher than generally appreciated and will increase as the population ages. Critical care capacity has long been needed in the developing world, and efforts to improve the care of the critically ill in these settings are starting to occur. Expansion of critical care to handle the consequences of an ageing population, natural disasters, conflict, inadequate primary care, and higher-risk medical therapies will be challenged by high costs at a time of economic constraint. To meet this challenge, investigators in this discipline will need to measure the global burden of critical illness and available critical-care resources, and develop both preventive and therapeutic interventions that are generalisable across countries.


Identification of Respiratory Viral Infection in Hematopoietic Stem Cell Transplant Recipients - Impact on Non Relapse Mortality


title: Challenges and strategies to research ethics in conducting COVID‐19 research

text: The number of research involving human subjects on coronavirus disease 2019 (COVID‐19) is surging, bringing challenges to the ethical review committee (ERC) in terms of reviewing speed and special ethical considerations under the pandemic. However, the existing ethical review system and regulations have their limitations to meet the demand for a prompt and efficient epidemic control. Since the research under the public health emergency is different from that carried out in familiar situations to design and implementation, the strategy for a satisfactory ERC response should balance the duty of protecting individual participants as well as the special public needs derived from the disease control. It is suggested that the ethical review‐related regulations need to be updated, and a unified supervision system to the overall ERC is required. ERC collaboration, capacity‐improving and efficiency‐improving measures need to be taken. With respect to the reviewing guidelines, it is suggested that the international norms should be explained with more consideration of the local condition and the exceptional circumstances in this public health emergency. A joint effort needs to be taken for better research conduction.


docid: hodykbcb

title: Viral Etiology of Chronic Obstructive Pulmonary Disease Exacerbations during the A/H1N1pdm09 Pandemic and Postpandemic Period

text: Viral infections are one of the main causes of acute exacerbations of chronic obstructive pulmonary disease (AE-COPD). Emergence of A/H1N1pdm influenza virus in the 2009 pandemic changed the viral etiology of exacerbations that were reported before the pandemic. The aim of this study was to describe the etiology of respiratory viruses in 195 Spanish patients affected by AE-COPD from the pandemic until the 2011-12 influenza epidemic. During the study period (2009–2012), respiratory viruses were identified in 48.7% of samples, and the proportion of viral detections in AE-COPD was higher in patients aged 30–64 years than ≥65 years. Influenza A viruses were the pathogens most often detected during the pandemic and the following two influenza epidemics in contradistinction to human rhino/enteroviruses that were the main viruses causing AE-COPD before the pandemic. The probability of influenza virus detection was 2.78-fold higher in patients who are 30–64 years old than those ≥65. Most respiratory samples were obtained during the pandemic, but the influenza detection rate was higher during the 2011-12 epidemic. There is a need for more accurate AE-COPD diagnosis, emphasizing the role of respiratory viruses. Furthermore, diagnosis requires increased attention to patient age and the characteristics of each influenza epidemic.


title: Creeping Through the Backdoor: Disruption in Medicine and Health

text: Can disruption happen when no one notices? Disruptive technologies and processes are fundamentally starting to up-end how medicines and health systems benefit patients but the question is whether health systems are ready for them. This paper will briefly review the business strategy and management literature on topics such as disruption and “black swan” theories of change, before turning to discuss some of the areas where change is affecting medicine and healthcare. Such areas include the emergence of cell and gene therapies, the economics of cures, digital technologies, mobile apps, social media, supply chain technologies such as drones and online distribution, universal health coverage and funding, and consumerisation of healthcare. The question to be asked is whether these sorts of changes are “disruptive” or whether they were coming for a long time and it is just that health systems are slow to change. It could be argued that while perhaps unexpected by day-to-day practitioners in healthcare, in fact, many of the changes now starting to affect the health and medicines sector have been affecting other sectors such as technology, finance and communications for decades.


Obesity and COVID-19: The Clash of Two Pandemics


title: A review of mathematical modeling, artificial intelligence and datasets used in the study, prediction and management of COVID-19

text: In the past few months, several works were published in regards to the dynamics and early detection of COVID-19 via mathematical modeling and Artificial intelligence (AI). The aim of this work is to provide the research community with comprehensive overview of the methods used in these studies as well as a compendium of available open source datasets in regards to COVID-19. In all, 61 journal articles, reports, fact sheets, and websites dealing with COVID-19 were studied and reviewed. It was found that most mathematical modeling done were based on the Susceptible-Exposed-Infected-Removed (SEIR) and Susceptible-infected-recovered (SIR) models while most of the AI implementations were Convolutional Neural Network (CNN) on X-ray and CT images. In terms of available datasets, they include aggregated case reports, medical images, management strategies, healthcare workforce, demography, and mobility during the outbreak. Both Mathematical modeling and AI have both shown to be reliable tools in the fight against this pandemic. Several datasets concerning the COVID-19 have also been collected and shared open source. However, much work is needed to be done in the diversification of the datasets. Other AI and modeling applications in healthcare should be explored in regards to this COVID-19.


docid: xlqzprqn

title: Hypothesized behavioral host manipulation by SARS-CoV2 / COVID-19 infection

text: Abstract Although not widely studied, behavioral host manipulation by various pathogens has been documented. Host manipulation is the process by which a pathogen evolves adaptations to manipulate the behavior of the host to maximize reproduction (Ro) of the pathogen. The most notable example is rabies. When a host is infected with the rabies virus it gets into the host’s central nervous system and triggers hyper aggression. The virus is also present in the rabid animal’s saliva so being bitten transmits the infection to a new host and the old host is left to eventually die if untreated. Toxoplasmosis is another example. When mice are infected they demonstrate a fearlessness toward cats, thus increasing their chances of being eaten. Toxoplasmosis needs the digestive tract of the feline to survive. Recent studies have shown that exposure to toxoplasmosis in humans (e.g., through cat feces) has also been associated with behavioral changes that are predicted to enhance the spread of the pathogen. Even the common influenza virus has been shown to selectively increase in-person sociality during the 48-hour incubation period, thus producing an obvious vector for transmission. Here we hypothesize that the novel coronavirus, SARS-CoV2, which produces the COVID-19 disease may produce similar host manipulations that maximize its transmission between humans.


title: Pneumonia in children admitted to the national referral hospital in Bhutan: A prospective cohort study

text: Abstract Objectives The study aim was to describe the etiological profile and clinical characteristics of pneumonia among children hospitalized in Thimphu, Bhutan. Methods This prospective study enrolled children aged 2–59 months admitted to the Jigme Dorji Wangchuck National Referral Hospital with World Health Organization (WHO)-defined clinical pneumonia. Demographic and clinico-radiological data were collected through questionnaires, physical examination, and chest radiography. Blood samples and nasopharyngeal washing were collected for microbiological analysis including culture and molecular methods. Results From July 2017 to June 2018, 189 children were enrolled, of which 53.4% were infants. Pneumonia-related admissions were less frequent over the winter. Chest radiographies were obtained in 149 children; endpoints included pneumonia in 39 cases (26.2%), other infiltrates in 31 (20.8%), and were normal in 79 children (53.0%). Non-contaminated bacterial growth was detected in 8/152 (5.3%) blood cultures, with only two cases of Streptococcus pneumoniae. Viral detection in upper respiratory secretions was common, with at least one virus detected in 103/115 (89.6%). The three most-commonly isolated viruses were respiratory syncytial virus (52/115; 45.2%), rhinovirus (42/115; 36.5%), and human parainfluenza virus (19/115; 16.5%). A third of patients with viral infections showed mixed infections. Case fatality rate was 3.2% (6/189). Conclusion Respiratory viral infections predominated among this cohort of WHO-defined clinical pneumonia cases, whereas bacterial aetiologies were uncommon, highlighting the epidemiologic transition that Bhutan seems to have reached.


title: Detection of the New Human Coronavirus HKU1: A Report of 6 Cases

text: Background. Human coronavirus HKU1 (HCoV-HKU1), a new group 2 coronavirus, was first characterized in 2005 from 2 adults with pneumonia in Hong Kong, China. To the best of our knowledge, there is no other report to date about the detection of this new virus. We report a molecular method allowing for the detection of HCoV-HKU1 and also report the clinical presentation of 6 infected patients. Methods. We screened 141 specimens (135 nasal samples and 6 stool samples) received in February and March 2005 in our laboratory and obtained from 135 hospitalized patients (61.5% of whom were <5 years old and 34.1% of whom were >20 years old) for HCoV-HKU1. Results. HCoV-HKU1 was detected in 6 (4.4%) of the 135 nasal specimens and in 2 (33.3%) of the 6 stool samples; the positive samples were obtained from 6 patients (5 children and 1 adult). The clinical presentation of these 6 patients was as follows: 3 were admitted to the hospital for acute enteric disease resulting in severe dehydration associated with upper respiratory symptoms; 1 had fever, otitis, and febrile seizure; 1 had a sample obtained to investigate failure to thrive; and 1 had a sample obtained for exploration of X-linked agammaglobulinemia and hyperleucocytosis. Conclusion. HCoV-HKU1 can be detected in respiratory and stool samples from children and adults in a part of the world other than Hong Kong. Our results suggest that HCoV-HKU1 could be associated with respiratory and enteric diseases, and its detection can be related to a persistent asymptomatic infection in patients with poor underlying conditions.