title: Central nervous system recruitment of effector memory CD8(+) T lymphocytes during neuroinflammation is dependent on α4 integrin

text: Clonally expanded CD8(+) T lymphocytes are present in multiple sclerosis lesions, as well as in the cerebrospinal fluid of patients with multiple sclerosis. In experimental autoimmune encephalomyelitis, CD8(+) T lymphocytes are found in spinal cord and brainstem lesions. However, the exact phenotype of central nervous system-infiltrating CD8(+) T lymphocytes and the mechanism by which these cells cross the blood–brain barrier remain largely unknown. Using cerebrospinal fluid from patients with multiple sclerosis, spinal cord from experimental autoimmune encephalomyelitis and coronavirus-induced encephalitis, we demonstrate that central nervous system-infiltrating CD8(+) T lymphocytes are mostly of the effector memory phenotype (CD62L(−) CCR7(−) granzymeB(hi)). We further show that purified human effector memory CD8(+) T lymphocytes transmigrate more readily across blood-brain barrier-endothelial cells than non-effector memory CD8(+) T lymphocytes, and that blood-brain barrier endothelium promotes the selective recruitment of effector memory CD8(+) T lymphocytes. Furthermore, we provide evidence for the recruitment of interferon-γ- and interleukin-17-secreting CD8(+) T lymphocytes by human and mouse blood-brain barrier endothelium. Finally, we show that in vitro migration of CD8(+) T lymphocytes across blood-brain barrier-endothelial cells is dependent on α4 integrin, but independent of intercellular adhesion molecule-1/leucocyte function-associated antigen-1, activated leucocyte cell adhesion molecule/CD6 and the chemokine monocyte chemotactic protein-1/CCL2. We also demonstrate that in vivo neutralization of very late antigen-4 restricts central nervous system infiltration of CD8(+) T lymphocytes in active immunization and adoptive transfer experimental autoimmune encephalomyelitis, and in coronavirus-induced encephalitis. Our study thus demonstrates an active role of the blood-brain barrier in the recruitment of effector memory CD8(+) T lymphocytes to the CNS compartment and defines α4 integrin as a major contributor of CD8(+) T lymphocyte entry into the brain.


title: Canine caliciviruses of four serotypes from military and research dogs recovered in 1963−1978 belong to two phylogenetic clades in the Vesivirus genus

text: BACKGROUND: Vesiviruses (family Caliciviridae) had been shown capable of invading a variety of host species, raising concern of their zoonotic potential. Since the 1980’s, several canine caliciviruses (CaCV) isolates have been reported and are phylogenetically related to the vesiviruses with features distinct from both Vesicular exanthema of swine virus (VESV) and Feline calicivirus (FCV) species in phylogeny, serology and cell culture specificities. Etiological studies of canine diseases in dogs used for military services and laboratory studies were conducted in 1963–1978 at the Walter Reed Army Institute of Research. Multiple known and unknown viral pathogens including caliciviruses were recovered. METHODS: Four unidentified isolates were recovered in Walter Reed Canine Cells (WRCC) from respiratory, fecal and penile specimens. Physicochemical tests, electron microscopy, viral cultivation in human and animal cells, antibody neutralization assays, and recently the genome sequencing were used to characterize the isolates. Sera from these dogs and their cohorts were tested with the isolates to determine origin and prevalence of the infections. RESULTS: The viral isolates were small non-enveloped spherical RNA virions, 27 to 42 nm in diameter with cup-like structures, indicating they are caliciviruses. They propagated in WRCC and MDCK cells, not in either other canine cells or human and other animal cells. Each isolate is antigenically distinct and react with dog sera in respective cohorts. The genomes have nucleotide identities ranging from 70.3% to 90.7% and encode the non-structural polyprotein (1810 amino acids), major capsid protein (691 amino acids) and minor structural protein (134 amino acids). They belong to two different phylogenetic clades in Vesivirus genus with close relation with canine calicivirus (CaCV). CONCLUSIONS: These CaCV isolates have restricted cell tropism, antigenic diversity and genetic variation. Further investigation will shed light on antigenic relation to other vesiviruses, and its pathogenicity for dogs and potential infectivity to other animals. Together with the previously reported CaCV strains provides significant evidence to support the formation of a new CaCV species in the Vesivirus genus. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0944-4) contains supplementary material, which is available to authorized users.


title: COVID‐19 and fiscal space for health system in Pakistan: It is time for a policy decision

text: Most developing countries with weak economies and low GDPs strive to invest an optimal amount of budget to health sector. Compounding on this state of affairs is their inherent inefficiency to spend even that meager amount on the welfare of the patients, improving service delivery, motivating their workforce and making their health systems responsive to the needs of the people they serve. With weak fiscal base and inelasticity in budget spending, when these countries face a catastrophe like COVID‐19, there is a whole situation of havoc and lack of finances emerges as the biggest issue in such crises. Pakistan has been no exception to this kind of situation. Government funds allocated to other public sector development schemes are diverted to deal with the health emergency. Hence, the result is an overall socioeconomic shock that a country has to face. Amid such crises, other international commitments also face a state of uncertainty. With the changing disease patterns all over the world, the public financial management system for health sector needs to be revisited to devise a more sustainable and resilient mechanism not only to absorb shocks like COVID‐19 but also to meet the international health commitments.


title: Critical role of cytochrome c1 and its cleavage in porcine reproductive and respiratory syndrome virus nonstructural protein 4-induced cell apoptosis via interaction with nsp4

text: Abstract Porcine reproductive and respiratory syndrome virus (PRRSV) actively induces cell apoptosis both in vitro and in vivo, which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 (nsp4) is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome c1 (cyto.c1) and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.c1 was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference (RNAi) silencing experiments further confirmed the crucial role which cyto.c1 played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.


title: Severe Acute Respiratory Syndrome (SARS): The Pharmacist's Role

text: Objectives. After two outbreaks of severe acute respiratory syndrome (SARS) occurred in Toronto, Ontario, Canada, from March–June 2003, we reviewed the unexpected role and responsibilities of pharmacists during these two crises, and present strategies for better crisis preparedness. Methods and Results. Pharmacists were actively involved in battling the SARS crises. After conducting extensive literature searches and evaluations, pharmacists prepared administration and dosing guidelines for the two investigational drugs, ribavirin and interferon alfacon‐1, that were being used to treat the syndrome. They provided direct patient care under modified conditions. They revised drug distribution procedures and developed new ones to meet more stringent infection‐control standards. Collaborative teamwork with key stakeholders was important in accomplishing tasks in an efficient and timely manner. Regular communication with health care staff took place internally and externally. Education and updated information for pharmacists was crucial. Conclusion. Pharmacists can play a vital role during crises in the areas of drug distribution, drug information, and direct patient care. Collaborative teamwork and close communication are keys to success. Pharmacists must be proactive and take a leadership role in assuming pharmacy‐related responsibilities. By evaluating what worked and what didn't, pharmacists can develop procedures for future crises requiring pharmacy support.


title: Snoek-type damping performance in strong and ductile high-entropy alloys

text: Noise and mechanical vibrations not only cause damage to devices, but also present major public health hazards. High-damping alloys that eliminate noise and mechanical vibrations are therefore required. Yet, low operating temperatures and insufficient strength/ductility ratios in currently available high-damping alloys limit their applicability. Using the concept of high-entropy alloy (HEA), we present a class of high-damping materials. The design is based on refractory HEAs, solid-solutions doped with either 2.0 atomic % oxygen or nitrogen, (Ta0.5Nb0.5HfZrTi)(98)O(2) and (Ta0.5Nb0.5HfZrTi)(98)N(2). Via Snoek relaxation and ordered interstitial complexes mediated strain hardening, the damping capacity of these HEAs is as high as 0.030, and the damping peak reaches up to 800 K. The model HEAs also exhibit a high tensile yield strength of ~1400 MPa combined with a large ductility of ~20%. The high-temperature damping properties, together with superb mechanical properties make these HEAs attractive for applications where noise and vibrations must be reduced.


title: 80-year-old man with dyspnoea and bilateral groundglass infiltrates: an elusive case of COVID-19

text: COVID-19 is a novel viral infection caused by severe acute respiratory syndrome-coronavirus-2 virus, first identified in Wuhan, China in December 2019. COVID-19 has spread rapidly and is now considered a global pandemic. We present a case of a patient with minimal respiratory symptoms but prominent bilateral groundglass opacities in a ‘crazy paving’ pattern on chest CT imaging and a negative initial infectious workup. However, given persistent dyspnoea and labs suggestive of COVID-19 infection, the patient remained hospitalised for further monitoring. Forty-eight hours after initial testing, the PCR test was repeated and returned positive for COVID-19. This case illustrates the importance of clinical vigilance to retest patients for COVID-19, particularly in the absence of another compelling aetiology. As COVID-19 testing improves to rapidly generate results, selective retesting of patients may uncover additional COVID-19 cases and strengthen measures to minimise the spread of COVID-19.


title: (18)F-FDG PET/CT in asymptomatic patients with COVID-19: the submerged iceberg surfaces

text: OBJECTIVE: The aim of this case series is to describe our experience in diagnosis and management of oncological asymptomatic patients with COVID-19 who underwent (18)F-FDG PET/CT. METHODS: From March 9 to March 31, 2020, we identified 5 patients who had PET/CT findings suspicious for COVID-19, but no symptom of infection. RESULTS: The first three patients were administered an SARS-CoV-2 test in a COVID-dedicated center, while the fourth and fifth were tested in our institution, in accordance with a new internal procedure. The SARS-CoV-2 test yielded positive results in all five patients. CONCLUSION: In this COVID-19 emergency, our task as radiologists and nuclear medicine physicians is to be able to identify imaging findings suggestive of the disease and to manage patients without overloading the hospital system.


title: Management of Patient Flow in Vascular and Interventional Radiology During MERS-CoV Outbreak

text: Abstract In 2015, an outbreak of Middle East respiratory syndrome coronavirus occurred in Saudi Arabia and necessitated special measures to be implemented to control the spread of the virus. In this article, we will discuss how the outbreak was managed in the vascular and interventional radiology (VIR) suite in a large tertiary care hospital in Saudi Arabia. Various measures were taken to reduce the risk of transmission of infection. Unit-level education played an important role in the care of patients. A hospital-wide educational program was implemented to ensure zero transmission of infection. Special attention was made to monitor staff who acquired the virus. VIR suite was able to handle the situation and control the outbreak.


title: Detecting Virus‐Like Particles from the Umgeni River, South Africa

text: It is important to consider viruses in water quality because of their incidence as causal agents for diarrhoeal disease, and due to their characteristics, which allow them to survive in changing environmental conditions indefinitely. This study assessed the viral quality of the Umgeni River in South Africa seasonally. A two‐step tangential flow filtration process was setup to remove the bacteria and to concentrate the virus populations from large volume water samples. The concentrated water samples contained up to 659 and 550 pfu/mL of somatic and F‐RNA coliphages, respectively. Several virus families including Adenoviridae, Herpesviridae, Orthomyxoviridae, Picornaviridae, Poxviridae and Reoviridae were found in the river based on the morphologies examined under transmission electron microscopy. All concentrated water samples produced substantial cytopathic effects on the Vero, HEK 293, Hela and A549 cell lines. These results indicate the potential of viruses in the water samples especially from the lower catchment areas of the Umgeni River to infect human hosts throughout the year. The present study highlights the importance of routine environmental surveillance of human enteric viruses in water sources. This can contribute to a better understanding of the actual burden of disease on those who might be using the water directly without treatment.


title: The Epitope and Neutralization Mechanism of AVFluIgG01, a Broad-Reactive Human Monoclonal Antibody against H5N1 Influenza Virus

text: The continued spread of highly pathogenic avian influenza (HPAI) H5N1 virus underscores the importance of effective antiviral approaches. AVFluIgG01 is a potent and broad-reactive H5N1-neutralizing human monoclonal antibody (mAb) showing great potential for use either for therapeutic purposes or as a basis of vaccine development, but its antigenic epitope and neutralization mechanism have not been finely characterized. In this study, we first demonstrated that AVFluIgG01 targets a novel conformation-dependent epitope in the globular head region of H5N1 hemagglutinin (HA). By selecting mimotopes from a random peptide library in combination with computational algorithms and site-directed mutagenesis, the epitope was mapped to three conserved discontinuous sites (I-III) that are located closely at the three-dimensional structure of HA. Further, we found that this HA1-specific human mAb can efficiently block both virus-receptor binding and post-attachment steps, while its Fab fragment exerts the post-attachment inhibition only. Consistently, AVFluIgG01 could inhibit HA-mediated cell-cell membrane fusion at a dose-dependent manner and block the acquisition of pH-induced protease sensitivity. These results suggest a neutralization mechanism of AVFluIgG01 by simultaneously blocking viral attachment to the receptors on host cells and interfering with HA conformational rearrangements associated with membrane fusion. The presented data provide critical information for developing novel antiviral therapeutics and vaccines against HPAI H5N1 virus.


title: Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo

text: Porcine epidemic diarrhea virus (PEDV) causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as Epimedium koreanum Nakai and Lonicera japonica Thunberg, respectively. The further plaque and CPE inhibition assay in vitro showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.


title: The Genome Landscape of the African Green Monkey Kidney-Derived Vero Cell Line

text: Continuous cell lines that originate from mammalian tissues serve as not only invaluable tools for life sciences, but also important animal cell substrates for the production of various types of biological pharmaceuticals. Vero cells are susceptible to various types of microbes and toxins and have widely contributed to not only microbiology, but also the production of vaccines for human use. We here showed the genome landscape of a Vero cell line, in which 25,877 putative protein-coding genes were identified in the 2.97-Gb genome sequence. A homozygous ∼9-Mb deletion on chromosome 12 caused the loss of the type I interferon gene cluster and cyclin-dependent kinase inhibitor genes in Vero cells. In addition, an ∼59-Mb loss of heterozygosity around this deleted region suggested that the homozygosity of the deletion was established by a large-scale conversion. Moreover, a genomic analysis of Vero cells revealed a female Chlorocebus sabaeus origin and proviral variations of the endogenous simian type D retrovirus. These results revealed the genomic basis for the non-tumourigenic permanent Vero cell lineage susceptible to various pathogens and will be useful for generating new sub-lines and developing new tools in the quality control of Vero cells.


Covid-19 in South Korea — Challenges of Subclinical Manifestations


title: The origins of cellular life

text: All life on earth can be naturally classified into cellular life forms and virus-like selfish elements, the latter being fully dependent on the former for their reproduction. Cells are reproducers that not only replicate their genome but also reproduce the cellular organization that depends on semipermeable, energy-transforming membranes and cannot be recovered from the genome alone, under the famous dictum of Rudolf Virchow, Omnis cellula e cellula. In contrast, simple selfish elements are replicators that can complete their life cycles within the host cell starting from genomic RNA or DNA alone. The origin of the cellular organization is the central and perhaps the hardest problem of evolutionary biology. I argue that the origin of cells can be understood only in conjunction with the origin and evolution of selfish genetic elements. A scenario of precellular evolution is presented that involves cohesion of the genomes of the emerging cellular life forms from primordial pools of small genetic elements that eventually segregated into hosts and parasites. I further present a model of the coevolution of primordial membranes and membrane proteins, discuss protocellular and non-cellular models of early evolution, and examine the habitats on the primordial earth that could have been conducive to precellular evolution and the origin of cells.


title: Psychological stress of medical staffs during outbreak of COVID‐19 and adjustment strategy

text: COVID‐19 has a significant impact on public health and poses a challenge to medical staffs, especially to front‐line medical staffs who are exposed to direct contact with patients. To understand the psychological stress status of medical staffs during the outbreak of COVID‐19. Random sample questionnaire survey was conducted among 2110 medical staffs and 2158 college students in all provinces of china through a questionnaire which was compiled and completed through the Questionnaire Star platform relying on Wechat, QQ and other social software. The differences in psychological stress status of different groups were compared through the analysis of the questionnaire. Results revealed that in all provinces of china, medical staffs scored significantly higher on all items of psychological stress than college students(P<0.001). In Wuhan, medical staff scored significantly higher than college students in all items of psychological stress(P<0.001). While for medical staff, the group in Wuhan area scored significantly higher than the group outside Wuhan on "Thought of being in danger", "The possibility of self‐illness", "Worrying about family infection"(P<0.05), "Poor sleep quality", "Needing psychological guidance" and "Worrying about being infected"(P<0.01) items in the psychological stress questionnaire, and in the item of "Confidence in the victory of the epidemic", the group in Wuhan area scored significantly lower than the group in the area outside Wuhan(P<0.05). The emotion, cognition, physical and mental response of front‐line medical staff showed obvious "exposure effect", and psychological crisis intervention strategy can be helpful. This article is protected by copyright. All rights reserved.


title: Epidemiological and clinical features of human metapneumovirus in hospitalised paediatric patients with acute respiratory illness: a cross-sectional study in Southern China, from 2013 to 2016

text: OBJECTIVES: Human metapneumovirus (HMPV) is one of the most important respiratory viral pathogens affecting infants and children worldwide. Our study describes the epidemiological and clinical characteristics of HMPV present in patients hospitalised with acute respiratory illness (ARI) in Guangzhou, Southern China. STUDY DESIGN: A cross-sectional study. SETTING: Two tertiary hospitals in Guangzhou. PARTICIPANTS AND METHODS: Throat swabs were collected over a 3-year period from 5133 paediatric patients (≤14 years) hospitalised with ARI. Patients who are HMPV positive with clinical presentations (101/103) were recorded for further analysis. RESULTS: Of the 5133 patients included in the study, 103 (2.0%) were positive for HMPV. HMPV was more prevalent in children ≤5 years (2.2%, 98/4399) compared with older children (>5–14 years) (0.7%, 5/734) (P=0.004). Two seasonal HMPV peaks were observed each year and mainly occurred in spring and early summer. Overall, 18.4% (19/103) of patients who are HMPV positive were codetected with other pathogens, most frequently respiratory syncytial virus (36.8%, 7/19). Patients who are HMPV positive presented with a wide spectrum of clinical features, including cough (100.0%, 101/101), abnormal pulmonary breath sound (91.1%, 92/101), fever (88.1%, 89/101), expectoration (77.2%, 78/101), coryza (50.5%, 51/101) and wheezing (46.5%, 47/101). The main diagnosis of patients who are HMPV positive was bronchopneumonia (66.7%, 56/84). Fever (≥38˚C) (91.6%, 76/83) was detected more often in patients with only HMPV detected than in patients with HMPV plus other pathogen(s) detected (72.2%, 13/18) (P=0.037), whereas diarrhoea was more common in patients with HMPV plus other pathogen(s) detected (22.2%, 4/18), compared with patients with HMPV only (3.6%, 3/83) (P=0.018). CONCLUSIONS: HMPV is an important respiratory pathogen in children with ARI in Guangzhou, particularly in children ≤5 years old. HMPV has a seasonal variation. Bronchopneumonia is a major diagnosis in patients who are HMPV positive.


How Has COVID‐19 Impacted Your Work?


title: The history of respiratory disease management

text: Abstract Over the past 200 years lung diseases have shifted from infections – tuberculosis, pneumonia – to diseases of dirty air – chronic obstructive pulmonary disease, asthma and lung cancer. New diseases have emerged from industrial pollution and HIV infection, while better imaging has revealed others previously unrecognized. Scientific advances in microbiology, imaging and clinical measurement have improved diagnosis and allowed better targeted treatment. Advances in treatment have been dramatic, the most important being drugs (antibiotics, cortisone, β2-adrenoceptor agonists), ventilatory support (from iron lung to nasal positive-pressure ventilation), inhaled therapy (metered dose inhalers, nebulizers) and lung surgery (resections, video-assisted thoracoscopic surgery, transplantation). Delivery of care has shifted from sanatoria for the rich but nothing at all for the poor, to universal coverage in both primary and hospital care. Generalists have turned into super-specialists and doctors have been joined by growing numbers of professions allied to medicine. Management of lung disease has vastly improved but the impact of disease remains.


title: Globalisation in the time of COVID-19: repositioning Africa to meet the immediate and remote challenges

text: The COVID-19 pandemic has ushered in a new climate of uncertainty which is fuelling protectionism and playing into nationalist narratives. Globalisation is under significant threat as governments scramble to reduce their vulnerability to the virus by limiting global trade and flows of people. With the imposition of border closures and strict migration measures, there have been major disruptions in Africa’s global supply chains with adverse impacts on employment and poverty. The African economies overly reliant on single export-orientated industries, such as oil and gas, are expected to be severely hit. This situation is further aggravated by tumbling oil prices and a lowered global demand for African non-oil products. The agricultural sector, which should buffer these shocks, is also being affected by the enforcement of lockdowns which threaten people’s livelihoods and food security. Lockdowns may not be the answer in Africa and the issue of public health pandemic response will need to be addressed by enacting context-specific policies which should be implemented in a humane way. In addressing the socioeconomic impact of COVID-19 on African nations, we argue that governments should prioritize social protection programmes to provide people with resources to maintain economic productivity while limiting job losses. International funders are committing assistance to Africa for this purpose, but generally as loans (adding to debt burdens) rather than as grants. G20 agreement so suspend debt payments for a year will help, but is insufficient to fiscal need. Maintaining cross-border trade and cooperation to continue generating public revenues is desirable. New strategies for diversifying African economies and limiting their dependence on external funding by promoting trade with a more regionalised (continental) focus as promoted by the African Continental Free Trade Agreement, while not without limitations, should be explored. While it is premature to judge the final economic and death toll of COVID-19, African leaders’ response to the pandemic, and the support they receive from wealthier nations, will determine its eventual outcomes.


title: Green Chemicals from Used Cooking Oils: Trends, Challenges and Opportunities

text: Food waste reduction is fundamental for sustainable development and pursuing this goal, recycling and the valorization of used cooking oil (UCO) can play a major contribution. Although it has been traditionally used for biofuels production, the oleochemical potential of UCOs is vast. UCOs can be used as feedstock for a large variety of value added green chemicals including plasticizers, binders, epoxides, surfactants, lubricants, polymers, biomaterials, and different building blocks. Thus, UCOs transformation into functional chemicals can bring long-term stability to the supply chain, avoiding the current dependence on commodity products. In this regard, this work describes some of the potential benefits of using UCOs as feedstock in oleochemical biorefineries. Also, some of the most recent investigations on the valorization of UCOs other than biofuel are presented. Finally, major challenges and future directions are discussed.


title: Detection of three human adenovirus species in adults with acute respiratory infection in China

text: Human adenoviruses (HAdVs) are recognized as causal agents in a wide range of human diseases. However, researchers lack sufficient data on the exact HAdV species and serotypes associated with adult acute respiratory tract infections (ARTIs). To detect and characterize HAdV infections in adults in China, clinical specimens were collected from 10,310 adults with ARTIs from May 2005 to July 2010. The partial HAdV hexon gene was amplified by polymerase chain reaction (PCR), sequenced, and phylogenetically analyzed. HAdVs were detected in 86 samples (0.8%), of which 67 (77.9%) were species B (HAdV-3, -7, -11, and -14), 7 (8.1%) were species C (HAdV-1, -2, and -6), and 12 (14%) were species E (HAdV-4). HAdV-3 was the most frequently detected serotype (41/86, 47.7%), followed by HAdV-7 (13/86, 15.1%), HAdV-4 (12/86, 14.0%), and HAdV-11 (11/86, 12.8%). Patients 14–25 years old (60.5%) exhibited a higher rate of adenovirus detection than older patients. Co-infections with other respiratory viruses were observed in samples positive for HAdV species B and E. Human rhinovirus was the most commonly found virus in patients with HAdV infection. These findings provide baseline data for the surveillance and control of HAdV infection in China.


title: Agent-based modeling of host–pathogen systems: The successes and challenges

text: Abstract Agent-based models have been employed to describe numerous processes in immunology. Simulations based on these types of models have been used to enhance our understanding of immunology and disease pathology. We review various agent-based models relevant to host–pathogen systems and discuss their contributions to our understanding of biological processes. We then point out some limitations and challenges of agent-based models and encourage efforts towards reproducibility and model validation.


title: Experimental study on a comprehensive particle swarm optimization method for locating contaminant sources in dynamic indoor environments with mechanical ventilation

text: Abstract Source localization is critical to ensuring indoor air quality and environmental safety. Although considerable research has been conducted on source localization in steady-state indoor environments, very few studies have dealt with the more challenging source localization problems in dynamic indoor environments. This paper presents a comprehensive particle swarm optimization (CPSO) method to locate a contaminant source in dynamic indoor environments with mechanical ventilation and develops a multi-robot source localization system to experimentally validate the method. Three robots were used to test the presented method in a typical dynamic indoor environment with periodic swinging of the air supply louvers of a cabinet air conditioner. The presented method was validated with two typical source locations, DS (in the downwind zone) and RS (in the recirculation zone). For DS and RS, 15 and 14 experiments out of 15 experiments were successful, with success rates of 100% and 93.3%, and each robot moved an average of 24.4 and 23.6 steps, respectively. The presented method was also compared with the standard particle swarm optimization (SPSO) and wind utilization II (WUII) methods for locating the source at DS. For the SPSO and WUII methods, only 3 and 6 experiments out of 15 experiments were successful, with success rates of 20% and 40% and averages of 33.0 and 38.0 steps, respectively. The experimental results show that the presented method not only has a much higher success rate than the SPSO and WUII methods but also has higher source localization efficiency.


title: Polymerase chain reaction combined with fluorescent lateral flow immunoassay based on magnetic purification for rapid detection of canine parvovirus 2

text: BACKGROUND: Canine parvovirus 2 (CPV-2) is one of the most common etiological agents that cause severe gastroenteritis in puppies. Early accurate diagnosis is important for infected dogs. In recent years, magnetic separation has become an efficient and useful tool for bioassays. In this study, polymerase chain reaction (PCR) combined with fluorescent lateral flow immunoassay (LFIA) based on magnetic purification assay was developed for the quantitative detection of CPV-2. RESULTS: The optimum working reaction volume and reaction time for LFIA was 100 μL and 2 min, respectively. The PCR-LFIA assay only detected CPV-2, and did not show cross-detection of non-CPV strains. Experiments showed analytical sensitivity of 3 × 10(1) copies/μL and demonstrated the PCR-LFIA has a diagnostic agreement of 100% with conventional PCR on detection of clinical samples (22.6% positive, 14/62). Cutoff value is 146. The results were further verified by sequencing and BLAST software. The entire process from PCR step only takes ~ 80 min. CONCLUSIONS: This approach provides an attractive platform for rapid and quantitative detection of CPV-2, indicating great promise as a convenient molecular detection tool to facilitate disease outbreak investigations and response timely.


title: Update on asthma prevalence in severe COVID‐19 patients

text: We carefully read the recently published research letter “Is asthma protective of COVID‐19?” by Carli et al.(1) with great interest. Important topics for asthma patients during the coronavirus disease 2019 (COVID‐19) pandemic were discussed, including that until recently there was limited evidence that patients with chronic respiratory disorders are at lower risk of being infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) or becoming severely ill.


Examining the impact of COVID‐19 on cardiac surgery services: The lessons learned from this pandemic


title: COVID-19 social distancing and sexual activity in a sample of the British Public

text: BACKGROUND: On 23rd March 2020 the UK government released self-isolation guidance to reduce the risk of transmission of SARS-Cov-2. The influence such guidance has on sexual activity is not known. AIM: To investigate levels and correlates of sexual activity during COVID-19 self-isolation in a sample of the UK public. METHODS: This paper presents pre-planned interim analyses of data from a cross-sectional epidemiological study, administered through an online survey. OUTCOMES: Sexual activity was measured using the following question: “On average after self-isolating how many times have you engaged in sexual activity weekly?” Demographic and clinical data was collected, including sex, age, marital status, employment, annual household income, region, current smoking status, current alcohol consumption, number of chronic physical conditions, number of chronic psychiatric conditions, any physical symptom experienced during self-isolation, and number of days of self-isolation. The association between several factors (independent variables) and sexual activity (dependent variable) was studied using a multivariable logistic regression model. RESULTS: 868 individuals were included in this study. There were 63.1% of women, and 21.8% of adults who were aged between 25 and 34 years. During self-isolation, 39.9% of the population reported engaging in sexual activity at least once per week. Variables significantly associated with sexual activity (dependent variable) were being male, a younger age, being married or in a domestic partnership, consuming alcohol, and a higher number of days of self-isolation/social distancing. CLINICAL IMPLICATIONS: In this sample of 868 UK adults self-isolating owing to the COVID-19 pandemic the prevalence of sexual activity was lower than 40%. Those reporting particularly low levels of sexual activity included females, older adults, those not married, and those who abstain from alcohol consumption. STRENGTH AND LIMITATIONS: This is the first study to investigate sexual activity during the UK COVID-19 self-isolation/social distancing. Participants were asked to self-report their sexual activity potentially introducing self-reporting bias into the findings. Second, analyses were cross-sectional and thus it is not possible to determine trajectories of sexual activity during the current pandemic. CONCLUSION: Interventions to promote health and wellbeing during the COVID-19 pandemic should consider positive sexual health messages in mitigating the detrimental health consequences in relation to self-isolation and should target those with the lowest levels of sexual activity.


title: Viruses of Lower Vertebrates

text: Viruses of lower vertebrates recently became a field of interest to the public due to increasing epizootics and economic losses of poikilothermic animals. These were reported worldwide from both wildlife and collections of aquatic poikilothermic animals. Several RNA and DNA viruses infecting fish, amphibians and reptiles have been studied intensively during the last 20 years. Many of these viruses induce diseases resulting in important economic losses of lower vertebrates, especially in fish aquaculture. In addition, some of the DNA viruses seem to be emerging pathogens involved in the worldwide decline in wildlife. Irido‐, herpes‐ and polyomavirus infections may be involved in the reduction in the numbers of endangered amphibian and reptile species. In this context the knowledge of several important RNA viruses such as orthomyxo‐, paramyxo‐, rhabdo‐, retro‐, corona‐, calici‐, toga‐, picorna‐, noda‐, reo‐ and birnaviruses, and DNA viruses such as parvo‐, irido‐, herpes‐, adeno‐, polyoma‐ and poxviruses, is described in this review.


docid: xqlngxuo

title: Vancomycin Monotherapy May Be Insufficient to Treat Methicillin-resistant Staphylococcus aureus Coinfection in Children With Influenza-related Critical Illness

text: BACKGROUND: Coinfection with influenza virus and methicillin-resistant Staphylococcus aureus (MRSA) causes life-threatening necrotizing pneumonia in children. Sporadic incidence precludes evaluation of antimicrobial efficacy. We assessed the clinical characteristics and outcomes of critically ill children with influenza–MRSA pneumonia and evaluated antibiotic use. METHODS: We enrolled children (<18 years) with influenza infection and respiratory failure across 34 pediatric intensive care units 11/2008–5/2016. We compared baseline characteristics, clinical courses, and therapies in children with MRSA coinfection, non-MRSA bacterial coinfection, and no bacterial coinfection. RESULTS: We enrolled 170 children (127 influenza A, 43 influenza B). Children with influenza–MRSA pneumonia (N = 30, 87% previously healthy) were older than those with non-MRSA (N = 61) or no (N = 79) bacterial coinfections. Influenza–MRSA was associated with increased leukopenia, acute lung injury, vasopressor use, extracorporeal life support, and mortality than either group (P ≤ .0001). Influenza-related mortality was 40% with MRSA compared to 4.3% without (relative risk [RR], 9.3; 95% confidence interval [CI], 3.8–22.9). Of 29/30 children with MRSA who received vancomycin within the first 24 hours of hospitalization, mortality was 12.5% (N = 2/16) if treatment also included a second anti-MRSA antibiotic compared to 69.2% (N = 9/13) with vancomycin monotherapy (RR, 5.5; 95% CI, 1.4, 21.3; P = .003). Vancomycin dosing did not influence initial trough levels; 78% were <10 µg/mL. CONCLUSIONS: Influenza–MRSA coinfection is associated with high fatality in critically ill children. These data support early addition of a second anti-MRSA antibiotic to vancomycin in suspected severe cases.


title: Pulmonary Infection

text: Virtually all infections that affect man can manifest within the lung. Pulmonary infection is the leading cause of death worldwide. The approach to the diagnosis and treatment of pulmonary infection requires a sound knowledge of both the microbial pathogens but also how the host immune system responds to infection.


Microvascular injury and hypoxic damage: emerging neuropathological signatures in COVID-19


title: Prevalence and contribution of respiratory viruses in the community to rates of emergency department visits and hospitalizations with respiratory tract infections, chronic obstructive pulmonary disease and asthma

text: BACKGROUND: The individual and combined contribution of viral prevalence in the community to Emergency Department (ED) visits and hospitalizations with respiratory tract infections (RTIs), chronic obstructive pulmonary disease (COPD) and asthma is unclear. METHODS: A retrospective analysis on daily viral positive tests and daily ED visits and hospitalizations between 01/01/2003 to 31/12/2013 in Ontario, Canada. Viral data was collected from the Centre for Immunization and Respiratory Infectious Diseases (CIRID). The Canadian Institute for Health Information reports daily ED visits and hospitalizations for RTIs, COPD and asthma as a primary diagnosis. RESULTS: There were 4,365,578 ED visits with RTIs of which 321,719 (7.4%) were admitted to hospital; 817,141 ED visits for COPD of which 260,665 (31.9%) were admitted and 649,666 ED visits with asthma of which 68,626 (10.6%) were admitted. The percentage of positive tests to influenza A and B, respiratory syncytial virus (RSV), parainfluenza and adenovirus prevalence explained 57.4% of ED visits and 63.8% of hospitalizations for RTI, 41.4% of ED visits and 39.2% of hospitalizations with COPD but only 1.5% of ED visits and 2.7% of hospitalizations for asthma. The further addition of human metapneumovirus, rhinovirus and coronavirus over the final 3 years accounted for 66.7% of ED visits and 74.4% of hospitalizations for RTI, 52.5% of visits and 48.2% of hospitalizations for COPD, and only 13.3% of visits and 10.4% of hospitalizations for asthma. CONCLUSIONS: Community respiratory viral epidemics are major drivers of ED visits and hospitalizations with RTIs and COPD but only a modest contributor to asthma.


title: A systematic review and meta-analysis of the epidemiology of pathogenic Escherichia coli of calves and the role of calves as reservoirs for human pathogenic E. coli

text: Escherichia coli bacteria are the most common causes of diarrhea and septicemia in calves. Moreover, calves form a major reservoir for transmission of pathogenic E. coli to humans. Systematic reviews and meta-analyses of publications on E. coli as calf pathogens and the role of calves as reservoir have not been done so far. We reviewed studies between 1951 and 2013 reporting the presence of virulence associated factors (VAFs) in calf E. coli and extracted the following information: year(s) and country of sampling, animal number, health status, isolate number, VAF prevalence, serotypes, diagnostic methods, and biological assays. The prevalence of VAFs or E. coli pathotypes was compared between healthy and diarrheic animals and was analyzed for time courses. Together, 106 papers with 25,982 E. coli isolates from 27 countries tested for VAFs were included. F5, F17, and F41 fimbriae and heat-stable enterotoxin (ST) – VAFs of enterotoxigenic E. coli (ETEC) were significantly associated with calf diarrhea. On the contrary, ETEC VAF F4 fimbriae and heat-labile enterotoxin as well as enteropathogenic (EPEC), Shiga toxin-producing (STEC), and enterohemorrhagic E. coli (EHEC) were not associated with diarrhea. The prevalence increased overtime for ST-positive isolates, but decreased for F5- and STEC-positive isolates. Our study provides useful information about the history of scientific investigations performed in this domain so far, and helps to define etiological agents of calf disease, and to evaluate calves as reservoir hosts for human pathogenic E. coli.


title: Evaluation of Public Health Emergency Management in China: A Systematic Review

text: To summarize the present status of health emergency management assessment in China, a comprehensive search of Chinese databases for research that explicitly mention health emergency assessment indicators and indicator systems was performed. Studies were evaluated using the Ekman quality assessment tool, and data were extracted with an original extraction form. Sixty-one studies were included. There are many types and methods of health emergency management assessment in China, and the dimensions and the indicators involved are complex. Legal, regulatory, and policy bases for such assessment need to be further strengthened. The relevance of the entire assessment process and its practical application should be enhanced. In the occupational practice, appropriate evaluation methods should be selected according to respective evaluation purposes, evaluation objects, and contents. Laws, regulations, and policies in the evaluation of health emergency management should be improved. Finally, further correlational research on health emergency management evaluation system processes should be explored and improved.


title: Epidemiological and clinical analysis of community-acquired Mycoplasma pneumonia in children from a Spanish population, 2010–2015

text: Abstract Introduction and objectives Mycoplasma pneumoniae (MP) is one of the most common etiological agents of community-acquired pneumonia (CAP) in children. We aimed to describe the clinical and epidemiological characteristics, treatment and outcome of children diagnosed with community-acquired MP pneumonia (CAMP) in a tertiary hospital in Valencia, Spain. Material and methods Medical records of children <14 years with CAMP were retrospectively reviewed from January 2010 to December 2015. Patients with radiological evidence of pneumonia and microbiological confirmation of MP (PCR from nasopharyngeal swab and/or serum specific IgM) were considered CAMP. Results One hundred and sixty two children were diagnosed with CAMP; median age 6 years (IQR: 4–9). The positive MP test rate among children with CAP progressively increased with age as did the empirical use of macrolides. There were two peaks of cases in 2011 and in 2015, being July, August, November and December the seasons with the higher number of cases. The most frequent radiological pattern was segmental infiltrate (62.3%) and 22 (13.6%) children had pleural effusion. It was noteworthy the mild symptomatology and low levels of inflammatory parameters that children with CAMP had. A macrolide was empirically initiated in 68.5% of cases. Hospital admission rate was inversely proportional to patient's age. Conclusions According to this study, older, less symptomatic patients and with lower inflammatory parameters had the greatest rate of MP infection among children with CAP and thus they could benefit of empiric macrolide therapy. Therefore, knowing the epidemiology of a geographical area may be important for the management of CAP in children.


title: Knowledge and Attitudes Among Hospital Pharmacists About COVID-19

text: Objectives: Coronavirus (COVID-19) cases and deaths related to the virus have been reported all over the world Pharmacists play an important role in conveying accurate information about COVID-19 to the community The aim of this study was to evaluate the knowledge and attitudes among hospital pharmacists about COVID-19 Materials and Methods: A questionnaire was distributed to pharmacists participating in the 7th National Hospital and Institution Pharmacists Congress The questions included in this questionnaire were created using the Turkish COVID-19 Scientific Committee guideline (COVID-19 Guideline) Results: Analysis of 237 questionnaires (72 6% completed by women) showed that the media (television, newspaper), internet (nonscientific resources), internet (scientific resources), and social media were the most popular sources of information (60 3%, 53 6%, 53 2%, and 41 4%, respectively) The participants' age and the source of information that they used had an important influence on their knowledge of and attitudes towards COVID-19 infection The majority of the participants (72 6%) stated that they were not wearing any kind of mask Transmission of the disease by airborne route was well known by the participants (91 1%), as well as the main symptoms such as fever (92 4%), cough (84 4%), and dyspnea (60 3%) The participants were aware of the risk groups for COVID-19 infection such as advanced age (84 8%) and having comorbidities (80 2%) Washing hands with soap (92 0%), using hand disinfectants (80 6%), and avoiding contact with sick people (81 9%) were popular answers for protection from the disease, but wearing an N95 mask was also mentioned by 59 1% of the participants Prevention of the disease by rinsing the nose with saline solution was believed in by 43 9% of the participants Conclusion: Classical media and social media affect the attitudes of both the public and health professionals Using media tools for accurate information is one of the basic conditions for preventing and controlling the spread of the disease


title: Human metapneumovirus: a new respiratory pathogen

text: Human metapneumovirus is a recently recognized pathogen of acute respiratory tract infection (ARI) in children as well as elderly and immunocompromised adults. The virus belongs to the family Paramyxoviridae, sub family Pneumovirinae and genus Metapneumovirus. Through genetic analysis it has been characterized into two groups A and B which are further divided into four sub-lineages. The virus is difficult to grow in tissue culture and hence reverse transcriptase-polymerase chain reaction (RT-PCR) for N and L gene is the method of choice for diagnosis. The virus has been seen in all countries with seasonal distribution in winter months for temperate and spring/summer for tropical countries. F gene is the most conserved among different lineages and efforts are underway to design recombination vaccine using F gene.


title: Weather-Dependent Risk for Legionnaires’ Disease, United States

text: Using the Nationwide Inpatient Sample and US weather data, we estimated the probability of community-acquired pneumonia (CAP) being diagnosed as Legionnaires’ disease (LD). LD risk increases when weather is warm and humid. With warm weather, we found a dose-response relationship between relative humidity and the odds for LD. When the mean temperature was 60°–80°F with high humidity (>80.0%), the odds for CAP being diagnosed with LD were 3.1 times higher than with lower levels of humidity (<50.0%). Thus, in some regions (e.g., the Southwest), LD is rarely the cause of hospitalizations. In other regions and seasons (e.g., the mid-Atlantic in summer), LD is much more common. Thus, suspicion for LD should increase when weather is warm and humid. However, when weather is cold, dry, or extremely hot, empirically treating all CAP patients for LD might contribute to excessive antimicrobial drug use at a population level.


title: Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis

text: BACKGROUND: Anti-viral CD8 T-cell activity is enhanced and prolonged by CD4 T-cell-mediated help, but negatively regulated by inhibitory B7-H1 interactions. During viral encephalomyelitis, the absence of CD4 T cells decreases CD8 T cell activity and impedes viral control in the central nervous system (CNS). By contrast, the absence of B7-H1 enhances CD8 T-cell function and accelerates viral control, but increases morbidity. However, the relative contribution of CD4 T cells to CD8 function in the CNS, in the absence of B7-H1, remains unclear. METHODS: Wild-type (WT) and B7-H1(−/−) mice were infected with a gliatropic coronavirus and CD4 T cells depleted to specifically block T helper function in the CNS. Flow cytometry and gene expression analysis of purified T-cell populations from lymph nodes and the CNS was used to directly monitor ex vivo T-cell effector function. The biological affects of altered T-cell responses were evaluated by analysis of viral control and spinal-cord pathology. RESULTS: Increased anti-viral activity by CD8 T cells in the CNS of B7-H1(−/−) mice was lost upon depletion of CD4 T cells; however, despite concomitant loss of viral control, the clinical disease was less severe. CD4 depletion in B7-H1(−/−) mice also decreased inducible nitric oxide synthase expression by microglia and macrophages, consistent with decreased microglia/macrophage activation and reduced interferon (IFN)-γ. Enhanced production of IFN-γ, interleukin (IL)-10 and IL-21 mRNA was seen in CD4 T cells from infected B7-H1(−/−) compared with WT mice, suggesting that over-activated CD4 T cells primarily contribute to the increased pathology. CONCLUSIONS: The local requirement of CD4 T-cell help for CD8 T-cell function is not overcome if B7-H1 inhibitory signals are lost. Moreover, the increased effector activity by CD8 T cells in the CNS of B7-H1(−/−) mice is attributable not only to the absence of B7-H1 upregulation on major histocompatibility complex class I-presenting resident target cells, but also to enhanced local CD4 T-cell function. B7-H1-mediated restraint of CD4 T-cell activity is thus crucial to dampen both CD8 T-cell function and microglia/macrophage activation, thereby providing protection from T-cell-mediated bystander damage.


title: A procedure for setting up high‐throughput nanolitre crystallization experiments. Crystallization workflow for initial screening, automated storage, imaging and optimization

text: Crystallization trials at the Division of Structural Biology in Oxford are now almost exclusively carried out using a high‐throughput workflow implemented in the Oxford Protein Production Facility. Initial crystallization screening is based on nanolitre‐scale sitting‐drop vapour‐diffusion experiments (typically 100 nl of protein plus 100 nl of reservoir solution per droplet) which use standard crystallization screening kits and 96‐well crystallization plates. For 294 K crystallization trials the barcoded crystallization plates are entered into an automated storage system with a fully integrated imaging system. These plates are imaged in accordance with a pre‐programmed schedule and the resulting digital data for each droplet are harvested into a laboratory information‐management system (LIMS), scored by crystal recognition software and displayed for user analysis via a web‐based interface. Currently, storage for trials at 277 K is not automated and for imaging the crystallization plates are fed by hand into an imaging system from which the data enter the LIMS. The workflow includes two procedures for nanolitre‐scale optimization of crystallization conditions: (i) a protocol for variation of pH, reservoir dilution and protein:reservoir ratio and (ii) an additive screen. Experience based on 592 crystallization projects is reported.


title: RNA interference for antiviral therapy

text: Silencing gene expression through a process known as RNA interference (RNAi) has been known in the plant world for many years. In recent years, knowledge of the prevalence of RNAi and the mechanism of gene silencing through RNAi has started to unfold. It is now believed that RNAi serves in part as an innate response against invading viral pathogens and, indeed, counter silencing mechanisms aimed at neutralizing RNAi have been found in various viral pathogens. During the past few years, it has been demonstrated that RNAi, induced by specifically designed double‐stranded RNA (dsRNA) molecules, can silence gene expression of human viral pathogens both in acute and chronic viral infections. Furthermore, it is now apparent that in in vitro and in some in vivo models, the prospects for this technology in developing therapeutic applications are robust. However, many key questions and obstacles in the translation of RNAi into a potential therapeutic platform still remain, including the specificity and longevity of the silencing effect, and, most importantly, the delivery of the dsRNA that induces the system. It is expected that for the specific examples in which the delivery issue could be circumvented or resolved, RNAi may hold promise for the development of gene‐specific therapeutics. Copyright © 2006 John Wiley & Sons, Ltd.


title: Biosensors based on graphene oxide and its biomedical application

text: Abstract Graphene oxide (GO) is one of the most attributed materials for opening new possibilities in the development of next generation biosensors. Due to the coexistence of hydrophobic domain from pristine graphite structure and hydrophilic oxygen containing functional groups, GO exhibits good water dispersibility, biocompatibility, and high affinity for specific biomolecules as well as properties of graphene itself partly depending on preparation methods. These properties of GO provided a lot of opportunities for the development of novel biological sensing platforms, including biosensors based on fluorescence resonance energy transfer (FRET), laser desorption/ionization mass spectrometry (LDI-MS), surface-enhanced Raman spectroscopy (SERS), and electrochemical detection. In this review, we classify GO-based biological sensors developed so far by their signal generation strategy and provide the comprehensive overview of them. In addition, we offer insights into how the GO attributed in each sensor system and how they improved the sensing performance.


title: Low‐dose oral interferon alpha as prophylaxis against viral respiratory illness: a double‐blind, parallel controlled trial during an influenza pandemic year

text: BACKGROUND AND OBJECTIVE: Interferon alpha (IFNα) is a known antiviral agent. A double‐blind, placebo‐controlled clinical trial was conducted investigating the use of low‐dose oral interferon alpha for preventing acute viral respiratory illnesses. METHODS: Two hundred healthy adults aged 18–75 years were enrolled and completed weekly health data questionnaires to monitor for symptoms and impact of respiratory illness. Serum samples were tested for antibodies against influenza and other common respiratory viruses. RESULTS: Low‐dose oral IFNα prophylaxis did not reduce the incidence or impact of acute respiratory illness (ARI) or the impact of illness on daily activities. Post hoc analysis of participant subgroups, however, identified significant reductions in the incidence of ARI reported by males, those aged 50 years or more and those who received the 2009 seasonal influenza vaccine. Interferon alpha prophylaxis had a significant impact on the reporting of moderate‐to‐severe feverishness by the study population. Seropositive participants in the IFN group were more likely to report asymptomatic or mild symptoms compared with those in the placebo group who were more likely to report stronger symptoms. CONCLUSIONS: Low‐dose oral IFNα prophylaxis was not effective in limiting the overall incidence of ARI in our study population. However, there was evidence that prophylaxis reduced the severity of symptoms and had a beneficial effect in some subpopulations, including those who received the 2009 seasonal trivalent influenza vaccination.


docid: biqbsggu

title: Transcriptome Sequencing and Annotation for the Jamaican Fruit Bat (Artibeus jamaicensis)

text: The Jamaican fruit bat (Artibeus jamaicensis) is one of the most common bats in the tropical Americas. It is thought to be a potential reservoir host of Tacaribe virus, an arenavirus closely related to the South American hemorrhagic fever viruses. We performed transcriptome sequencing and annotation from lung, kidney and spleen tissues using 454 and Illumina platforms to develop this species as an animal model. More than 100,000 contigs were assembled, with 25,000 genes that were functionally annotated. Of the remaining unannotated contigs, 80% were found within bat genomes or transcriptomes. Annotated genes are involved in a broad range of activities ranging from cellular metabolism to genome regulation through ncRNAs. Reciprocal BLAST best hits yielded 8,785 sequences that are orthologous to mouse, rat, cattle, horse and human. Species tree analysis of sequences from 2,378 loci was used to achieve 95% bootstrap support for the placement of bat as sister to the clade containing horse, dog, and cattle. Through substitution rate estimation between bat and human, 32 genes were identified with evidence for positive selection. We also identified 466 immune-related genes, which may be useful for studying Tacaribe virus infection of this species. The Jamaican fruit bat transcriptome dataset is a resource that should provide additional candidate markers for studying bat evolution and ecology, and tools for analysis of the host response and pathology of disease.


title: SARS-CoV-2 in wastewater: State of the knowledge and research needs

text: Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a Public Health Emergency of International Concern, which was officially declared by the World Health Organization. SARS-CoV-2 is a member of the family Coronaviridae that consists of a group of enveloped viruses with single-stranded RNA genome, some of which have been known to cause common colds. Although the major transmission routes of SARS-CoV-2 are inhalation from person-to-person and aerosol/droplet transmission, currently available evidence indicates that the viral RNA is present in wastewater, suggesting the need to better understand wastewater as potential sources of epidemiological data and human health risks. Here, we review the current knowledge related to the potential of wastewater surveillance to understand the epidemiology of COVID-19, methodologies for the detection and quantification of SARS-CoV-2 in wastewater, and information relevant for human health risk assessment of SARS-CoV-2. There has been growing evidence of gastrointestinal symptoms caused by SARS-CoV-2 infections and the presence of viral RNA not only in feces of COVID-19 patients but in wastewater. One of the major challenges in SARS-CoV-2 detection/quantification in wastewater samples is the lack of an optimized and standardized protocol. Currently available data are also limited for conducting a quantitative microbial risk assessment (QMRA) for SARS-CoV-2 exposure pathways. However, modeling-based approaches have a potential role to play in reducing the impact of the ongoing COVID-19 outbreak, and QMRA parameters obtained from previous studies on relevant respiratory viruses help to inform risk assessments of SARS-CoV-2. Our understanding on the potential role of wastewater in SARS-CoV-2 transmission is largely limited by knowledge gaps in its occurrence, persistence, and removal in wastewater. There is an urgent need for further research to establish methodologies for wastewater surveillance and understand the implications of the presence of SARS-CoV-2 in wastewater.


Forum: Technology, Ecology, and Human Health Since 1850


title: Characterization of the fusion core in zebrafish endogenous retroviral envelope protein

text: Abstract Zebrafish endogenous retrovirus (ZFERV) is the unique endogenous retrovirus in zebrafish, as yet, containing intact open reading frames of its envelope protein gene in zebrafish genome. Similarly, several envelope proteins of endogenous retroviruses in human and other mammalian animal genomes (such as syncytin-1 and 2 in human, syncytin-A and B in mouse) were identified and shown to be functional in induction of cell–cell fusion involved in placental development. ZFERV envelope protein (Env) gene appears to be also functional in vivo because it is expressible. After sequence alignment, we found ZFERV Env shares similar structural profiles with syncytin and other type I viral envelopes, especially in the regions of N- and C-terminal heptad repeats (NHR and CHR) which were crucial for membrane fusion. We expressed the regions of N + C protein in the ZFERV Env (residues 459–567, including predicted NHR and CHR) to characterize the fusion core structure. We found N + C protein could form a stable coiled-coil trimer that consists of three helical NHR regions forming a central trimeric core, and three helical CHR regions packing into the grooves on the surface of the central core. The structural characterization of the fusion core revealed the possible mechanism of fusion mediated by ZFERV Env. These results gave comprehensive explanation of how the ancient virus infects the zebrafish and integrates into the genome million years ago, and showed a rational clue for discovery of physiological significance (e.g., medicate cell–cell fusion).


title: Chapter 5 Host Range, Host–Virus Interactions, and Virus Transmission

text: Summary Three intricate and intertwined biological features in the replication cycle of viruses are covered in this chapter: The range of cellular entities that support virus replication and/or virus transmission, and the various relationships viruses establish with their hosts and biological vectors. Although in its infancy, an explosion of research on virus–host interactions has already revealed surprising relationships ranging from strictly parasitic to mutualistic, and some others in between. A clearer picture is emerging as regards to our understanding of the full spectrum of these interactions, even with varying experimental approaches and differing opinions on terminology and data interpretation.


docid: mrgzrztc

title: Why diagnose respiratory viral infection?


title: Transition to a virtual multidisciplinary tumor board during the COVID‐19 pandemic: University of Pittsburgh experience

text: Multidisciplinary conferences (MDC) are an important component of head and neck oncologic care including diagnosis, treatment, and survivorship. Virtual MDC allows for improved collaboration between providers at distant sites and proper allocation of health care resources in a time of crisis. When approached systematically, a virtual MDC is feasible to design and implement in a large academic medical center with multiple satellite hospitals.


title: Do natural disasters cause an excessive fear of heights? Evidence from the Wenchuan earthquake

text: Abstract This paper uses the 2008 Wenchuan earthquake in China to examine if the occurrence of a natural disaster can cause an excessive fear of living in upper floors. We rely on potential variations in earthquake risk perceptions by floor level to assess whether the pricing of apartments in lower versus upper floors is consistent with a disproportionate fear of heights. We use a unique transaction dataset for new apartment units in the affected area. We find that the relative price of low to high floor units, particularly units located in the first and second floor, considerably increased for several months after the earthquake and then returned back to the levels observed prior to the tremor. This temporal increase in relative prices is in line with a higher risk perception and fear, triggered after the earthquake, of living in upper floors, which gradually dissipated over time. The results are robust to alternative model estimations.


docid: uejtwgar

title: Inhibition of Bruton tyrosine kinase in patients with severe COVID-19

text: Patients with severe COVID-19 have a hyperinflammatory immune response suggestive of macrophage activation. Bruton tyrosine kinase (BTK) regulates macrophage signaling and activation. Acalabrutinib, a selective BTK inhibitor, was administered off-label to 19 patients hospitalized with severe COVID-19 (11 on supplemental oxygen; 8 on mechanical ventilation), 18 of whom had increasing oxygen requirements at baseline. Over a 10-14 day treatment course, acalabrutinib improved oxygenation in a majority of patients, often within 1-3 days, and had no discernable toxicity. Measures of inflammation – C-reactive protein and IL-6 – normalized quickly in most patients, as did lymphopenia, in correlation with improved oxygenation. At the end of acalabrutinib treatment, 8/11 (72.7%) patients in the supplemental oxygen cohort had been discharged on room air, and 4/8 (50%) patients in the mechanical ventilation cohort had been successfully extubated, with 2/8 (25%) discharged on room air. Ex vivo analysis revealed significantly elevated BTK activity, as evidenced by autophosphorylation, and increased IL-6 production in blood monocytes from patients with severe COVID-19 compared with blood monocytes from healthy volunteers. These results suggest that targeting excessive host inflammation with a BTK inhibitor is a therapeutic strategy in severe COVID-19 and has led to a confirmatory international prospective randomized controlled clinical trial.


title: Polycations increase the efficiency of adenovirus-mediated gene transfer to epithelial and endothelial cells in vitro

text: Recombinant adenoviruses are being developed for gene therapy for cystic fibrosis and other lung diseases, and for prevention and treatment of vascular thrombosis. A major limitation to the clinical utility of adenoviruses is the low efficiency of gene transfer achieved in vivo. In addition, little is known about the initial interactions between adenoviruses and the target cell. To address the hypothesis that the negative charge presented by membrane glycoproteins reduces the efficiency of adenovirus-mediated gene transfer, primary cultures of human airway, Madin–Darby canine kidney cells, an immortalized cystic fibrosis airway epithelial cell line, and primary cultures of sheep pulmonary artery endothelium were infected with recombinant adeno- virus containing the E. coli lacZ reporter gene (Ad2βgal2) in the presence of various polyions. For each cell type, adsorption of Ad2βgal2 in the presence of the polycations polybrene, protamine, DEAE-dextran, and poly-L-lysine significantly increased the percentage of cells that express lacZ. The polyanion heparin did not significantly alter gene transfer efficiency, but completely abrogated the effects of polycations. These data provide evidence that negatively charged moieties on the cell surface reduce the efficiency of adenovirus-mediated gene transfer, and that alteration of the charge interaction between adenoviruses and the cell surface may improve the potential clinical application of these vectors.


title: Burden of serious fungal infections in the Netherlands

text: BACKGROUND: Fungal diseases have an ever‐increasing global disease burden, although regional estimates for specific fungal diseases are often unavailable or dispersed. OBJECTIVES: Here, we report the current annual burden of life‐threatening and debilitating fungal diseases in the Netherlands. METHODS: The most recent available epidemiological data, reported incidence and prevalence of fungal diseases were used for calculations. RESULTS: Overall, we estimate that the annual burden of serious invasive fungal infections in the Netherlands totals 3 185 patients, including extrapulmonary or disseminated cryptococcosis (n = 9), pneumocystis pneumonia (n = 740), invasive aspergillosis (n = 1 283), chronic pulmonary aspergillosis (n = 257), invasive Candida infections (n = 684), mucormycosis (n = 15) and Fusarium keratitis (n = 8). Adding the prevalence of recurrent vulvo‐vaginal candidiasis (n = 220 043), allergic bronchopulmonary aspergillosis (n = 13 568) and severe asthma with fungal sensitisation (n = 17 695), the total debilitating burden of fungal disease in the Netherlands is 254 491 patients yearly, approximately 1.5% of the country's population. CONCLUSION: We estimated the annual burden of serious fungal infections in the Netherlands at 1.5% of the population based on previously reported modelling of fungal rates for specific populations at risk. With emerging new risk groups and increasing reports on antifungal resistance, surveillance programmes are warranted to obtain more accurate estimates of fungal disease epidemiology and associated morbidity and mortality.


title: Estimated Demand for US Hospital Inpatient and Intensive Care Unit Beds for Patients With COVID-19 Based on Comparisons With Wuhan and Guangzhou, China

text: IMPORTANCE: Sustained spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has happened in major US cities. Capacity needs in cities in China could inform the planning of local health care resources. OBJECTIVES: To describe and compare the intensive care unit (ICU) and inpatient bed needs for patients with coronavirus disease 2019 (COVID-19) in 2 cities in China to estimate the peak ICU bed needs in US cities if an outbreak equivalent to that in Wuhan occurs. DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study analyzed the confirmed cases of COVID-19 in Wuhan and Guangzhou, China, from January 10 to February 29, 2020. EXPOSURES: Timing of disease control measures relative to timing of SARS-CoV-2 community spread. MAIN OUTCOMES AND MEASURES: Number of critical and severe patient–days and peak number of patients with critical and severe illness during the study period. RESULTS: In Wuhan, strict disease control measures were implemented 6 weeks after sustained local transmission of SARS-CoV-2. Between January 10 and February 29, 2020, patients with COVID-19 accounted for a median (interquartile range) of 429 (25-1143) patients in the ICU and 1521 (111-7202) inpatients with serious illness each day. During the epidemic peak, 19 425 patients (24.5 per 10 000 adults) were hospitalized, 9689 (12.2 per 10 000 adults) were considered in serious condition, and 2087 (2.6 per 10 000 adults) needed critical care per day. In Guangzhou, strict disease control measures were implemented within 1 week of case importation. Between January 24 and February 29, COVID-19 accounted for a median (interquartile range) of 9 (7-12) patients in the ICU and 17 (15-26) inpatients with serious illness each day. During the epidemic peak, 15 patients were in critical condition and 38 were classified as having serious illness. The projected number of prevalent critically ill patients at the peak of a Wuhan-like outbreak in US cities was estimated to range from 2.2 to 4.4 per 10 000 adults, depending on differences in age distribution and comorbidity (ie, hypertension) prevalence. CONCLUSIONS AND RELEVANCE: Even after the lockdown of Wuhan on January 23, the number of patients with serious COVID-19 illness continued to rise, exceeding local hospitalization and ICU capacities for at least a month. Plans are urgently needed to mitigate the consequences of COVID-19 outbreaks on the local health care systems in US cities.


docid: kmpbdvof

title: Antigen Production in Plant to Tackle Infectious Diseases Flare Up: The Case of SARS

text: Severe acute respiratory syndrome (SARS) is a dangerous infection with pandemic potential. It emerged in 2002 and its aetiological agent, the SARS Coronavirus (SARS-CoV), crossed the species barrier to infect humans, showing high morbidity and mortality rates. No vaccines are currently licensed for SARS-CoV and important efforts have been performed during the first outbreak to develop diagnostic tools. Here we demonstrate the transient expression in Nicotiana benthamiana of two important antigenic determinants of the SARS-CoV, the nucleocapsid protein (N) and the membrane protein (M) using a virus-derived vector or agro-infiltration, respectively. For the M protein, this is the first description of production in plants, while for plant-derived N protein we demonstrate that it is recognized by sera of patients from the SARS outbreak in Hong Kong in 2003. The availability of recombinant N and M proteins from plants opens the way to further evaluation of their potential utility for the development of diagnostic and protection/therapy tools to be quickly manufactured, at low cost and with minimal risk, to face potential new highly infectious SARS-CoV outbreaks.


title: Clinical Evaluation of the cobas SARS-CoV-2 Test and a Diagnostic Platform Switch during 48 Hours in the Midst of the COVID-19 Pandemic

text: Laboratories are currently witnessing extraordinary demand globally for sampling devices, reagents, consumables, and diagnostic instruments needed for timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To meet diagnostic needs as the pandemic grows, the U.S. Food and Drug Administration (FDA) recently granted several commercial SARS-CoV-2 tests Emergency Use Authorization (EUA), but manufacturer-independent evaluation data are scarce. We performed the first manufacturer-independent evaluation of the fully automated sample-to-result two-target test cobas 6800 SARS-CoV-2 (cobas) (Roche Molecular Systems, Branchburg, NJ), which received U.S. FDA EUA on 12 March 2020. The comparator was a standardized 3-h SARS-CoV-2 protocol, consisting of RNA extraction using an automated portable instrument, followed by a two-target reverse transcription real-time PCR (RT-PCR), which our laboratory has routinely used since January 2020 [V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25(3):pii=2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045]. cobas and the comparator showed overall agreement of 98.1% and a kappa value of 0.95 on an in-house validation panel consisting of 217 well-characterized retrospective samples. Immediate prospective head-to-head comparative evaluation followed on 502 samples, and the diagnostic approaches showed overall agreement of 99.6% and a kappa value of 0.98. A good correlation (r(2) = 0.96) between cycle threshold values for SARS-CoV-2-specific targets obtained by cobas and the comparator was observed. Our results showed that cobas is a reliable assay for qualitative detection of SARS-CoV-2 in nasopharyngeal swab samples collected in the Universal Transport Medium System (UTM-RT) (Copan, Brescia, Italy). Under the extraordinary circumstances that laboratories are facing worldwide, a safe diagnostic platform switch is feasible in only 48 h and in the midst of the COVID-19 pandemic if carefully planned and executed.


title: Structural Basis for Inhibiting Porcine Epidemic Diarrhea Virus Replication with the 3C-Like Protease Inhibitor GC376

text: Porcine epidemic diarrhea virus (PEDV), being highly virulent and contagious in piglets, has caused significant damage to the pork industries of many countries worldwide. There are no commercial drugs targeting coronaviruses (CoVs), and few studies on anti-PEDV inhibitors. The coronavirus 3C-like protease (3CL(pro)) has a conserved structure and catalytic mechanism and plays a key role during viral polyprotein processing, thus serving as an appealing antiviral drug target. Here, we report the anti-PEDV effect of the broad-spectrum inhibitor GC376 (targeting 3Cpro or 3CL(pro) of viruses in the picornavirus-like supercluster). GC376 was highly effective against the PEDV 3CL(pro) and exerted similar inhibitory effects on two PEDV strains. Furthermore, the structure of the PEDV 3CL(pro) in complex with GC376 was determined at 1.65 Å. We elucidated structural details and analyzed the differences between GC376 binding with the PEDV 3CL(pro) and GC376 binding with the transmissible gastroenteritis virus (TGEV) 3CL(pro). Finally, we explored the substrate specificity of PEDV 3CL(pro) at the P2 site and analyzed the effects of Leu group modification in GC376 on inhibiting PEDV infection. This study helps us to understand better the PEDV 3CL(pro) substrate specificity, providing information on the optimization of GC376 for development as an antiviral therapeutic against coronaviruses.


title: A high-throughput screening system for G-protein-coupled receptors using β-lactamase enzyme complementation technology

text: AIM: To establish a system for monitoring the activation of G-protein-coupled receptors (GPCRs) using β-lactamase enzyme fragment complementation (EFC) technology. METHODS: Two inactive β-lactamase deletion fragments, bla(a) and bla(b), were fused to β-arrestin and GPCR, respectively. A stable cell line named HEK/293-β2a2, which expressed two fusion proteins, GPCR/bla(b) and β-arrestin2/bla(a), was generated under antibiotic selection. A natural compound library of high performance liquid chromatography (HPLC)-fractionated samples from the ethanol extracts of Chinese medicinal herbs was used for high-throughput screening (HTS) of β2-adrenoceptor (β2AR) agonists against the cell line HEK/293-β2a2. The interested hits were validated by the measurement of second-messenger cyclic adenosine monophosphate (cAMP) production. RESULTS: The stable cell line HEK/293-β2a2 responded to β2AR agonist/antagonist in a dose-dependent manner. The EC(50) value obtained for isoproterenol was 15.5 nmol/L, and the IC(50) value obtained for propranolol was 51.9 nmol/L. Furthermore, HTS was performed to identify β2AR agonists from the natural compound library we established. The Z′ factor value was determined to be 0.68. Three hits were identified from primary screening and found to be as potent as isoproterenol in a cAMP assay. CONCLUSION: A cell-based high-throughput functional assay was established to directly monitor the activation of GPCRs based on the interaction between agonist-activated GPCR and β-arrestin using β-lactamase EFC technology, which can be used to search for leads in the natural compound library.


title: Enhancement of target-DNA hybridization efficiency by pre-hybridization on sequence-orientated micro-arrayed probes

text: Abstract The enhancement of hybridization efficiency of deoxyribonucleic acid (DNA) targets using oligonucleotide pre-hybridization is studied on two sequence-inversed micro-arrayed probes. The sequences for pre-hybridizing both oligo and target DNA are designed to be fully complementary with their shared DNA probe in a coaxial stacking configuration; i.e. they hybridize immediately alongside each other along the continuous complement probe strand. The pre-hybridizing oligo and target DNA are differentiated by being labeled with two distinct fluorescent dyes, and the cooperative effect on hybridization efficiency is investigated through the comparison of the stacking and individual hybridization configurations based on the detection signals of the labeling dyes. The results show that the pre-hybridization of a DNA oligo enhances the subsequent hybridization efficiency of the target-DNA coupling onto the same probe. The efficiency is enhanced if the hybridization position occurs at a site close to the substrate surface.


title: Nested-RT-PCR and Multiplex RT-PCR for Diagnosis of Rhinovirus Infection in Clinical Samples

text: Human rhinoviruses (HRVs) are positive-stranded RNA viruses belonging to the Enterovirus genus in the family of Picornaviridae. Identification of the specific strain in HRV disease has been difficult because the traditional serological method is insensitive, labor intensive, and cumbersome. With the fast progress in molecular biological technique, more sensitive and faster molecular methods have been developed, such as polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, and real-time RT-PCR. To improve the technique for defining the links between illnesses and specific strains of HRV, we developed RT-PCR specific for HRV as routine base. A multiplex RT-PCR that simultaneously identifies 12 respiratory viruses including HRV is also routinely used in our lab. Here we have described the specific steps of methods for identification of HRV from clinical samples, such as sample preparation, isolation of total RNA, nested-RT-PCR for HRV, Seeplex(®) RV15 ACE Detection method, gel electrophoresis, how to use the QIAxcel(®) capillary electrophoresis system, and results interpretation.


title: Bioinformatics analysis reveals four major hexon variants of human adenovirus type-3 (HAdV-3) as the potential strains for development of vaccine and siRNA-based therapeutics against HAdV-3 respiratory infections

text: Human adenovirus type 3 (HAdV-3) encompasses 15–87% of all adenoviral respiratory infections. The significant morbidity and mortality, especially among the neonates and immunosuppressed patients, demand the need for a vaccine or a targeted antiviral against this type. However, due to the existence of multiple hexon variants (3Hv-1 to 3Hv-25), the selection of vaccine strains of HAdV-3 is challenging. This study was designed to evaluate HAdV-3 hexon variants for the selection of potential vaccine candidates and the use of hexon gene as a target for designing siRNA that can be used as a therapy. Based on the data of worldwide distribution, duration of circulation, co-circulation and their percentage among all the variants, 3Hv-1 to 3Hv-4 were categorized as the major hexon variants. Phylogenetic analysis and the percentage of homology in the hypervariable regions followed by multi-sequence alignment, zPicture analysis and restriction enzyme analysis were carried out. In the phylogram, the variants were arranged in different clusters. The HVR encoding regions of hexon of 3Hv-1 to 3Hv-4 showed 16 point mutations resulting in 12 amino acids substitutions. The homology in HVRs was 81.81–100%. Therefore, the major hexon variants are substantially different from each other which justifies their inclusion as the potential vaccine candidates. Interestingly, despite the significant differences in the DNA sequence, there were many conserved areas in the HVRs, and we have designed functional siRNAs form those locations. We have also designed immunogenic vaccine peptide epitopes from the hexon protein using bioinformatics prediction tool. We hope that our developed siRNAs and immunogenic vaccine peptide epitopes could be used in the future development of siRNA-based therapy and designing a vaccine against HAdV-3.


title: Phages and HIV-1: From Display to Interplay

text: The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.


Changes in radiotherapy practice during COVID–19 outbreak in turkey: a report from the turkish society for radiation oncology


title: Covid‐19: Exposing the Lack of Evidence‐Based Practice in Medicine

text: The Covid‐19 pandemic has altered the shape of medicine, making in‐person interactions risky for both patients and health care workers. Now, before scheduling in‐person appointments or procedures, physicians are forced to reconsider if they are truly necessary. The pandemic has thus thrown into relief the difference between evidence‐based medical care and traditional aspects of care that lack a strong evidentiary component. In this essay, we demonstrate how this has played out in prenatal care, as well as in other aspects of medical care, during the pandemic. The extent to which these changes will persist beyond the most emergent phases of the pandemic is not clear, though insurance reimbursement practices and patient expectations will be determining factors. One thing, however, is certain: the longer the pandemic continues, the more difficult it will be for providers and patients to return to pre‐Covid norms.


title: Chest Computed Tomography for Detection of Coronavirus Disease 2019 (COVID-19): Don't Rush the Science

text: This commentary discusses the findings of early studies that addressed the use of chest computed tomography for the detection of COVID-19. The authors urge caution in rushing science and overinterpreting preliminary or flawed data.


title: The potential effects of widespread community transmission of SARS-CoV-2 infection in the World Health Organization African Region: a predictive model

text: The spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been unprecedented in its speed and effects. Interruption of its transmission to prevent widespread community transmission is critical because its effects go beyond the number of COVID-19 cases and deaths and affect the health system capacity to provide other essential services. Highlighting the implications of such a situation, the predictions presented here are derived using a Markov chain model, with the transition states and country specific probabilities derived based on currently available knowledge. A risk of exposure, and vulnerability index are used to make the probabilities country specific. The results predict a high risk of exposure in states of small size, together with Algeria, South Africa and Cameroon. Nigeria will have the largest number of infections, followed by Algeria and South Africa. Mauritania would have the fewest cases, followed by Seychelles and Eritrea. Per capita, Mauritius, Seychelles and Equatorial Guinea would have the highest proportion of their population affected, while Niger, Mauritania and Chad would have the lowest. Of the World Health Organization's 1 billion population in Africa, 22% (16%–26%) will be infected in the first year, with 37 (29 – 44) million symptomatic cases and 150 078 (82 735–189 579) deaths. There will be an estimated 4.6 (3.6–5.5) million COVID-19 hospitalisations, of which 139 521 (81 876–167 044) would be severe cases requiring oxygen, and 89 043 (52 253–106 599) critical cases requiring breathing support. The needed mitigation measures would significantly strain health system capacities, particularly for secondary and tertiary services, while many cases may pass undetected in primary care facilities due to weak diagnostic capacity and non-specific symptoms. The effect of avoiding widespread and sustained community transmission of SARS-CoV-2 is significant, and most likely outweighs any costs of preventing such a scenario. Effective containment measures should be promoted in all countries to best manage the COVID-19 pandemic.


title: IGF-1 Deficiency Rescue and Intracellular Calcium Blockade Improves Survival and Corresponding Mechanisms in a Mouse Model of Acute Kidney Injury

text: This study was undertaken to test two therapies for acute kidney injury (AKI) prevention, IGF-1, which is renal protective, and BTP-2, which is a calcium entry (SOCE) inhibitor. We utilized lipopolysaccharide (LPS) IP, as a systemic model of AKI and studied in five groups of animals. Three experiments showed that at 7 days: (1) LPS significantly reduced serum IGF-1 and intramuscular IGF-I in vivo gene therapy rescued this deficiency. (2) Next, at the 7-day time point, our combination therapy, compared to the untreated group, caused a significant increase in survival, which was noteworthy because all of the untreated animals died in 72 h. (3) The four pathways associated with inflammation, including (A) increase in cytosolic calcium, (B) elaboration of proinflammatory cytokines, (C) impairment of vascular integrity, and (D) cell injury, were adversely affected in renal tissue by LPS, using a sublethal dose of LPS. The expression of several genes was measured in each of the above pathways. The combined therapy of IGF-1 and BTP-2 caused a favorable gene expression response in all four pathways. Our current study was an AKI study, but these pathways are also involved in other types of severe inflammation, including sepsis, acute respiratory distress syndrome, and probably severe coronavirus infection.


title: Case report of COVID‐19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation?

text: COVID‐19 is novel infectious disease with an evolving understanding of its epidemiology and clinical manifestations. Immunocompromised patients often present atypical presentations of viral diseases. Herein we report a case of a COVID‐19 infection in a solid organ transplant recipient, in which the first clinical symptoms were of gastrointestinal viral disease and fever, which further progressed to respiratory symptoms in 48 hours. In these high risk populations, protocols for screening for SARS‐Cov2 may be needed to be re‐evaluated.


docid: tdrfcyhk

title: Using GRADE in situations of emergencies and urgencies: Certainty in evidence and recommendations matters during the COVID-19 pandemic, now more than ever and no matter what

text: ●. GRADEing the certainty of the available evidence is more important than ever because of the unprecedented pressure for action and the large number of people affected by decisions; ●. The GRADE approach is a transparent and structured method for assessing the certainty of evidence and when developing recommendations that requires little additional time; ●. In situations of emergencies and urgencies, such as the COVID-19 pandemic, GRADE can similarly be used to express and convey certainty in intervention effects, test accuracy, risk and prognostic factors, consequences of public health measures, and qualitative bodies of evidence; ●. Requirements for emergency, urgency, rapid and routine GRADE assessment may differ but should transition from one to another.


title: Colitis as a Sole Presentation of SARS-CoV-2 Infection: Case Report

text: On March 11, 2020, COVID-19 was declared as a pandemic by World Health Organization. Criteria for identifying persons under investigation for SARS-CoV-2 infection by Centers for Disease Control and Prevention remain focusing on fever and respiratory symptoms. We report a case of COVID-19 patient who presented with colitis alone.


title: Epidemiology of virus-induced asthma exacerbations: with special reference to the role of human rhinovirus

text: Viral respiratory infections may be associated with the virus-induced asthma in adults as well as children. Particularly, human rhinovirus is strongly suggested a major candidate for the associations of the virus-induced asthma. Thus, in this review, we reviewed and focused on the epidemiology, pathophysiology, and treatment of virus-induced asthma with special reference on human rhinovirus. Furthermore, we added our preliminary data regarding the clinical and virological findings in the present review.


title: New information technology (IT)-related approaches could facilitate psychiatric treatments in general hospital psychiatry during the COVID-19 pandemic

text: • Impact of the COVID-19 pandemic on psychiatric conditions has been increasing. • “Tablet visit” for inpatients has been introduced. • For outpatients, an online visit system has been used.


The disproportionate effect of COVID-19 mortality on ethnic minorities: Genetics or health inequalities?


docid: ayacjojb

title: Role of Cellular Lipids in Positive-Sense RNA Virus Replication Complex Assembly and Function

text: Positive-sense RNA viruses are responsible for frequent and often devastating diseases in humans, animals, and plants. However, the development of effective vaccines and anti-viral therapies targeted towards these pathogens has been hindered by an incomplete understanding of the molecular mechanisms involved in viral replication. One common feature of all positive-sense RNA viruses is the manipulation of host intracellular membranes for the assembly of functional viral RNA replication complexes. This review will discuss the interplay between cellular membranes and positive-sense RNA virus replication, and will focus specifically on the potential structural and functional roles for cellular lipids in this process.


title: Proteomics Analysis of the DF-1 Chicken Fibroblasts Infected with Avian Reovirus Strain S1133

text: BACKGROUND: Avian reovirus (ARV) is a member of the Orthoreovirus genus in the Reoviridae family. It is the etiological agent of several diseases, among which viral arthritis and malabsorption syndrome are the most commercially important, causing considerable economic losses in the poultry industry. Although a small but increasing number of reports have characterized some aspects of ARV infection, global changes in protein expression in ARV-infected host cells have not been examined. The current study used a proteomics approach to obtain a comprehensive view of changes in protein levels in host cells upon infection by ARV. METHODOLOGY AND PRINCIPAL FINDINGS: The proteomics profiles of DF-1 chicken fibroblast cells infected with ARV strain S1133 were analyzed by two-dimensional differential-image gel electrophoresis. The majority of protein expression changes (≥1.5 fold, p<0.05) occurred at 72 h post-infection. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identified 51 proteins with differential expression levels, including 25 that were upregulated during ARV infection and 26 that were downregulated. These proteins were divided into eight groups according to biological function: signal transduction, stress response, RNA processing, the ubiquitin-proteasome pathway, lipid metabolism, carbohydrate metabolism, energy metabolism, and cytoskeleton organization. They were further examined by immunoblotting to validate the observed alterations in protein expression. CONCLUSION/SIGNIFICANCE: This is the first report of a time-course proteomic analysis of ARV-infected host cells. Notably, all identified proteins involved in signal transduction, RNA processing, and the ubiquitin-proteasome pathway were downregulated in infected cells, whereas proteins involved in DNA synthesis, apoptosis, and energy production pathways were upregulated. In addition, other differentially expressed proteins were linked with the cytoskeleton, metabolism, redox regulation, and stress response. These proteomics data provide valuable information about host cell responses to ARV infection and will facilitate further studies of the molecular mechanisms underlying ARV pathogenesis.