title: Biodiversity Conservation and the Earth System: Mind the Gap

text: One of the most striking human impacts on global biodiversity is the ongoing depletion of large vertebrates from terrestrial and aquatic ecosystems. Recent work suggests this loss of megafauna can affect processes at biome or Earth system scales with potentially serious impacts on ecosystem structure and function, ecosystem services, and biogeochemical cycles. We argue that our contemporary approach to biodiversity conservation focuses on spatial scales that are too small to adequately address these impacts. We advocate a new global approach to address this conservation gap, which must enable megafaunal populations to recover to functionally relevant densities. We conclude that re-establishing biome and Earth system functions needs to become an urgent global priority for conservation science and policy.


title: SARS-CoV-2–A Tough Opponent for the Immune System

text: Coronaviruses recently returned with a new one, SARS-CoV-2, related to a potentially severe respiratory disease-called the coronavirus disease (COVID-19). Research shows that the SARS-CoV-2 can be clustered with the Bat SARS-like coronavirus. Bats possess an additional, innate ability for antiviral defense, and, on the other hand, the potential to go hand-in-hand with the virus to generate variability. Besides the high potential of the novel coronavirus in compromising the respiratory system, its rapid transmission and ability to engage many hosts in severe forms of infections or immunopathological complications make it a tough opponent for the immune system. The interactions between SARS-CoV2 and the host immune system result in unleashing tremendous amounts of cytokines, and these cytokines make a storm that would determine the outcome (recovery or death) of the lungs of the patient.


title: Identification of gammaherpesvirus infection in free-ranging black bears (Ursus americanus)

text: Abstract Herpesvirus infection was investigated in black bears (Ursus americanus) with neurological signs and brain lesions of nonsuppurative encephalitis of unknown cause. Visible cytopathic effects (CPE) could only be observed on days 3–5 post-infection in HrT-18G cell line inoculated with bear tissue extracts. The observed CPE in HrT-18G cells included syncytia, intranuclear inclusions, and cell detachments seen in herpesvirus infection in vitro. Herpesvirus-like particles were observed in viral culture supernatant under the electron microscope, however, capsids ranging from 60 nm to 100 nm in size were often observed in viral cultures within the first two passages of propagation. Herpesvirus infection in the bear tissues and tissue cultures were detected by PCR using degenerate primers specific to the DNA polymerase gene (DPOL) and glycoprotein B gene (gB). DNA sequencing of the amplicon revealed that the detected herpesvirus has 94–95% identity to Ursid gammaherpesvirus 1 (UrHV-1) DNA sequences of DPOL. Phylogenetic analysis of DPOL sequences indicates that black bear herpesviruses and UrHV-1 are closely related and have small distances to members of Rhadinovirus. Interestingly, black bear herpesvirus infections were also found in bears without neurological signs. The DPOL DNA sequence of black bear herpesviruses detected in neurological bears were similar to the those detected in the non-neurological bears. However, the gB DNA sequence detected from the neurological bear is different from non-neurological bear and has only 64.5%–70% identity to each other. It is possible that at least two different types of gammaherpesviruses are present in the U. americanus population or several gammaherpesviruses exist in ursine species.


title: Leadership of the Department of Epidemiology of the Johns Hopkins Bloomberg School of Public Health in Its First Century

text: This commentary reviews the contributions of each of the 7 Chairs of the Department of Epidemiology from the Department's inception in 1919 to the advent of the Centennial Celebration of the Johns Hopkins Bloomberg School of Public Health in 2016. The founding Chair, Wade Hampton Frost (1919–1938), was among the handful of foundational thinkers in the discipline of epidemiology. Kenneth Maxcy (1938–1954) and Philip Sartwell (1954–1970) oversaw the Department through the epidemiologic transition from a preponderance of morbidity and mortality due to infectious diseases to a preponderance of noncommunicable diseases. Abraham Lilienfeld (1970–1975) and Leon Gordis (1975–1993) were perhaps best known for their mastery of teaching, influencing generations of both medical and public health students. Jonathan Samet (1994–2008) oversaw a major curriculum revision and expanded the Department significantly, and David Celentano (2008–) is working to rebalance the practice of epidemiology with the etiological foundations of epidemiology. All Chairs were a product of their times, and their research focus and portfolios influenced the direction of the Department. Future generations of Johns Hopkins students will be influenced directly or indirectly by the heritage of these Chairs' actions and those of their faculty.


title: Personality Traits, Risk Perception, and Protective Behaviors of Arab Residents of Qatar During the COVID-19 Pandemic

text: During the 2020 COVID-19 pandemic, people in Qatar—similar to most countries globally—were instructed by health authorities to adopt protective behaviors to avoid infection. One of these behaviors is social distancing, which is influenced by diverse variables. Using data from an online survey with 405 responses, this study performed multiple regression analysis to explore effects of personality, risk perception, and personal hygiene practices on social distancing among residents of Qatar. The results showed that 87.3% of participants reported that they preferred to stay at home and not go outside unless necessary, 60.3% said that they maintain an adequate distance when communicating with others, 68.6% reported that they do not allow relatives and friends to visit them at home, 73.5% believed that COVID-19 is a dangerous disease, and 95.8% reported that they embrace personal hygiene practices and washing hands. Furthermore, multiple regression analysis showed that conscientiousness, neuroticism, risk perception, and personal hygiene practices predicted social distancing, with moderate effect sizes. Gender differences were also found in social distancing practices, indicating that women reported higher engagement in social distancing practices than men. These results highlighted the importance of individual differences in reacting to the COVID-19 pandemic and provide important information about the predictors of social distancing practices.


title: Underused coronavirus tests, controversial vaccine study and Arctic emergency

text: When scientists were planning MOSAiC — a pioneering expedition that would trap a research vessel in Arctic sea ice for one year — they considered the North Pole’s hazards But no one anticipated a pandemic


title: Existence theory and numerical analysis of three species prey–predator model under Mittag-Leffler power law

text: In this manuscript, the fractional Atangana–Baleanu–Caputo model of prey and predator is studied theoretically and numerically. The existence and Ulam–Hyers stability results are obtained by applying fixed point theory and nonlinear analysis. The approximation solutions for the considered model are discussed via the fractional Adams Bashforth method. Moreover, the behavior of the solution to the given model is explained by graphical representations through the numerical simulations. The obtained results play an important role in developing the theory of fractional analytical dynamic of many biological systems.


Arterial hypertension and risk of death in patients with COVID-19 infection: systematic review and meta-analysis


title: Biochemical and Structural Insights into the Mechanisms of SARS Coronavirus RNA Ribose 2′-O-Methylation by nsp16/nsp10 Protein Complex

text: The 5′-cap structure is a distinct feature of eukaryotic mRNAs, and eukaryotic viruses generally modify the 5′-end of viral RNAs to mimic cellular mRNA structure, which is important for RNA stability, protein translation and viral immune escape. SARS coronavirus (SARS-CoV) encodes two S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTase) which sequentially methylate the RNA cap at guanosine-N7 and ribose 2′-O positions, catalyzed by nsp14 N7-MTase and nsp16 2′-O-MTase, respectively. A unique feature for SARS-CoV is that nsp16 requires non-structural protein nsp10 as a stimulatory factor to execute its MTase activity. Here we report the biochemical characterization of SARS-CoV 2′-O-MTase and the crystal structure of nsp16/nsp10 complex bound with methyl donor SAM. We found that SARS-CoV nsp16 MTase methylated m7GpppA-RNA but not m7GpppG-RNA, which is in contrast with nsp14 MTase that functions in a sequence-independent manner. We demonstrated that nsp10 is required for nsp16 to bind both m7GpppA-RNA substrate and SAM cofactor. Structural analysis revealed that nsp16 possesses the canonical scaffold of MTase and associates with nsp10 at 1∶1 ratio. The structure of the nsp16/nsp10 interaction interface shows that nsp10 may stabilize the SAM-binding pocket and extend the substrate RNA-binding groove of nsp16, consistent with the findings in biochemical assays. These results suggest that nsp16/nsp10 interface may represent a better drug target than the viral MTase active site for developing highly specific anti-coronavirus drugs.


title: Nosocomial infections among patients with COVID-19, SARS and MERS: A rapid review and meta-analysis

text: Background: COVID-19, a disease caused by SARS-CoV-2 coronavirus, has now spread to most countries and regions of the world. As patients potentially infected by SARS-CoV-2 need to visit hospitals, the incidence of nosocomial infection can be expected to be high. Therefore, a comprehensive and objective understanding of nosocomial infection is needed to guide the prevention and control of the epidemic. Methods: We searched major international and Chinese databases: Medicine, Web of Science, Embase, Cochrane, CBM (China Biology Medicine disc), CNKI (China National Knowledge Infrastructure) and Wanfang database for case series or case reports on nosocomial infections of COVID-19, SARS (severe acute respiratory syndromes) and MERS (Middle East respiratory syndrome) from their inception to March 31st, 2020. We conducted a meta-analysis of the proportion of nosocomial infection patients in the diagnosed patients, occupational distribution of nosocomial infection medical staff. Results: We included 40 studies. Among the confirmed patients, the proportions of nosocomial infections with early outbreaks of COVID-19, SARS, and MERS were 44.0%, 36.0%, and 56.0%, respectively. Of the confirmed patients, the medical staff and other hospital-acquired infections accounted for 33.0% and 2.0% of COVID-19 cases, 37.0% and 24.0% of SARS cases, and 19.0% and 36.0% of MERS cases, respectively. Nurses and doctors were the most affected among the infected medical staff. The mean numbers of secondary cases caused by one index patient were 29.3 and 6.3 for SARS and MERS, respectively. Conclusions: The proportion of nosocomial infection in patients with COVID-19 was 44% in the early outbreak. Patients attending hospitals should take personal protection. Medical staff should be awareness of the disease to protect themselves and the patients.


title: Mental health of health-care workers in the COVID-19 era

text: Health-care workers involved in the response to the COVID-19 pandemic are often required to work in highly challenging conditions and may therefore be at increased risk of experiencing mental health problems. This Comment sets out a practical approach to protecting the mental health of health-care workers based on contemporary evidence.


title: Bakterielle oder virale Atemwegsentzündung? Neuer Bedside-Test hilft weiter

text: Bei Verdacht auf akute Atemwegsinfektion kann ein Bedside-Test, der auf 20 gängige Lungenpathogene testet und Ergebnisse in einer Stunde liefert, unnötige Krankenhaus- und Antibiotika-Behandlungen verhindern.


title: Use of recombinant nucleocapsid proteins for serological diagnosis of feline coronavirus infection by three immunochromatographic tests

text: Abstract Three types of immunochromatographic assays (ICAs) were designed to detect anti-feline coronavirus (FCoV) antibodies. Recombinant FCoV nucleocapsid protein (rNP) was used as a conjugate or test line in all 3 ICA kits (CJIgG/TNP, CJNP/TNP, and CJNP/TPA). All three ICA kits were capable of detecting anti-FCoV antibodies; however, non-specific positive reactions of anti-FCoV antibody-negative plasma samples with the test line were observed in 2 ICA kits (CJIgG/TNP and CJNP/TNP), in which rNP was used as the test line. On the other hand, the specific detection of anti-FCoV antibodies was possible in all plasma, serum, whole blood, and ascitic fluid samples using the ICA kit with protein A blotted as the test line (CJNP/TPA). In addition, the specificity and sensitivity of ICA (CJNP/TPA) were equivalent to those of the reference ELISA. The development of simple antibody test methods using the principle of ICA (CJNP/TPA) for other coronavirus and feline viral infections is expected in the future.


title: Treatment of post‐viral olfactory dysfunction: an evidence‐based review with recommendations

text: BACKGROUND: Post‐viral olfactory dysfunction (PVOD) is one of the most common causes of olfactory loss. Despite its prevalence, optimal treatment strategies remain unclear. This article provides a comprehensive review of PVOD treatment options and provides evidence‐based recommendations for their use. METHODS: A systematic review of the Medline, Embase, Cochrane, Web of Science, Scopus, and Google Scholar databases was completed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Studies with defined olfactory outcomes of patients treated for PVOD following medical, surgical, acupuncture, or olfactory training interventions were included. The Clinical Practice Guideline Development Manual and Conference on Guideline Standardization (COGS) instrument recommendations were followed in accordance with a previously described, rigorous, iterative process to create an evidence‐based review with recommendations. RESULTS: From 552 initial candidate articles, 36 studies with data for 2183 patients with PVOD were ultimately included. The most common method to assess olfactory outcomes was Sniffin’ Sticks. Broad treatment categories included: olfactory training, systemic steroids, topical therapies, a variety of heterogeneous non‐steroidal oral medications, and acupuncture. CONCLUSION: Based on the available evidence, olfactory training is a recommendation for the treatment of PVOD. The use of short‐term systemic and/or topical steroids is an option in select patients after careful consideration of potential risks of oral steroids. Though some pharmacological investigations offer promising preliminary results for systemic and topical medications alike, a paucity of high‐quality studies limits the ability to make meaningful evidence‐based recommendations for the use of these therapies for the treatment of PVOD.


docid: wlrcaypa

title: SAGES primer for taking care of yourself during and after the COVID-19 crisis

text: COVID-19 is a pandemic which has affected almost every aspect of our life since starting globally in November 2019. Given the rapidity of spread and inadequate time to prepare for record numbers of sick patients, our surgical community faces an unforeseen challenge. SAGES is committed to the protection and care of patients, their surgeons and staff, and all who are served by the medical community at large. This includes physical health, mental health, and well-being of all involved. The fear of the unknown ahead can be paralyzing. International news media have chronicled the unthinkable situations that physicians and other health care providers have been thrust into as a result of the COVID-19 pandemic. These situations include making life or death decisions for patients and their families regarding use of limited health care resources. It includes caring for patients with quickly deteriorating conditions and limited treatments available. Until recently, these situations seemed far from home, and now they are in our own hospitals. As the pandemic broadened its reach, the reality that we as surgeons may be joining the front line is real. It may be happening to you now; it may be on the horizon in the coming weeks. In this context, SAGES put together this document addressing concerns on clinician stressors in these times of uncertainty. We chose to focus on the emotional toll of the situation on the clinician, protecting vulnerable persons, reckoning with social isolation, and promoting wellness during this crisis. At the same time, the last part of this document deals with the “light at the end of the tunnel,” discussing potential opportunities, lessons learned, and the positives that can come out of this crisis.


title: Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

text: Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders.


title: Nucleotide sequence of the gene encoding the membrane protein of human coronavirus 229 E

text: The sequence of the gene encoding the membrane protein of human coronavirus 229 E (HCV 229 E) has been determined. The primary translation product, deduced from the DNA sequence, is a polypeptide of 225 amino acids with a predicted molecular weight of 26,000. The polypeptide has 3 potential N-glycosylation sites. Many structural similarities with the membrane proteins of other coronaviruses can be recognized.


title: Impact of RSV Coinfection on Human Bocavirus in Children with Acute Respiratory Infections

text: OBJECTIVE: The objective of this study was to assess epidemiological and clinical features of human bocavirus (HBoV) coinfection with other viruses. METHOD: Children coinfected with HBoV between January 2012 and December 2014 were enrolled and retrospectively reviewed. RESULT: A total of 984 patients were stratified into five groups: HBoV infection alone (n = 249), respiratory syncytial virus (RSV) infection alone (n = 649), HBoV coinfection with RSV (n = 28), with human rhinovirus (HRV) (n = 39) and with other virus (n = 19). Length of hospitalization was longer in HBoV coinfection with RSV group than HBoV (9.0 days vs. 7.0 days, p = 0.001), RSV (9.0 days vs. 8.0 days, p = 0.016) infection alone group. Pneumonia was more common in the HBoV coinfection with RSV group compared with the HBoV, RSV infection alone group, respectively (75.0% vs. 44.2%, 31.3%, p < 0.001). HBoV DNA copy numbers (383 000 copies/ml) were positively correlated with the length of hospitalization (r = 0.334, p < 0.001). CONCLUSION: HBoV coinfection with RSV increases HBoV infection severity.


title: Assessing Climate Change Impact on Ecosystems and Infectious Disease: Important Roles for Genomic Sequencing and a One Health Perspective

text: Changes in the Earth’s climate and weather continue to impact the planet’s ecosystems, including the interface of infectious disease agents with their hosts and vectors. Environmental disasters, natural and human-made activities raise risk factors that indirectly facilitate infectious disease outbreaks. Subsequently, changes in habitat, displaced populations, and environmental stresses that affect the survival of species are amplified over time. The recurrence and spread of vector-borne (e.g., mosquito, tick, aphid) human, animal, and plant pathogens to new geographic locations are also influenced by climate change. The distribution and range of humans, agricultural animals and plants, wildlife and native plants, as well as vectors, parasites, and microbes that cause neglected diseases of the tropics as well as other global regions are also impacted. In addition, genomic sequencing can now be applied to detect signatures of infectious pathogens as they move into new regions. Molecular detection assays complement metagenomic sequencing to help us understand the microbial community found within the microbiomes of hosts and vectors, and help us uncover mechanistic relationships between climate variability and pathogen transmission. Our understanding of, and responses to, such complex dynamics and their impacts can be enhanced through effective, multi-sectoral One Health engagement coupled with applications of both traditional and novel technologies. Concerted efforts are needed to further harness and leverage technology that can identify and track these impacts of climate changes in order to mitigate and adapt to their effects.


Avec le Covid-19, une ère nouvelle se dessine


Cardiovascular surgery in the COVID‐19 pandemic


title: Zanamivir versus trivalent split virus influenza vaccine: a pilot randomized trial

text: BACKGROUND: Healthcare workers may be exposed to people with respiratory viral infections more often than other working adults. Understanding the risk and the effectiveness of different preventive measures is of great importance. OBJECTIVES: To estimate adherence to prophylactic antiviral medication for a full influenza season, to the compare efficacy of antiviral prophylaxis to that of the seasonal influenza vaccine and to identify exposures that increase risk of acute respiratory illnesses (ARI) in healthy adults. METHODS: Participants were randomized 1:2 to receive the 2008–2009 influenza vaccine or daily prophylaxis with 10 mg of zanamivir during the season. Web-based questionnaires collected information on demographics, symptoms, exposures, medication use and side effects. RESULTS: Sixty-four healthy adults were recruited in November 2008. Three of 40 active participants discontinued zanamivir due to side effects; the remaining 37 took >85% of scheduled doses for a median of 121 days. Symptomatic, laboratory-confirmed influenza was detected in one person randomized to zanamivir (2·5%) and 2/20 (10%) who received the vaccine (P = 0·25). Forty-seven participants reported 109 episodes of ARI. Factors associated with an ARI were exposure to a spouse (OR 7·2), child (OR 2·4) or patient (OR 2·0) with symptoms of an ARI in the previous 7 days. CONCLUSIONS: Breakthrough influenza infection occurred in both vaccinated participants and those receiving antiviral prophylaxis. Most adults were willing and able to comply with season-long prophylaxis. Report of recent exposure to family members and patients with an ARI increased the risk of developing an ARI in healthy adults.


title: Horizontal Gene Transfers with or without Cell Fusions in All Categories of the Living Matter

text: This article reviews the history of widespread exchanges of genetic segments initiated over 3 billion years ago, to be part of their life style, by sphero-protoplastic cells, the ancestors of archaea, prokaryota, and eukaryota. These primordial cells shared a hostile anaerobic and overheated environment and competed for survival. “Coexist with, or subdue and conquer, expropriate its most useful possessions, or symbiose with it, your competitor” remain cellular life’s basic rules. This author emphasizes the role of viruses, both in mediating cell fusions, such as the formation of the first eukaryotic cell(s) from a united crenarchaeon and prokaryota, and the transfer of host cell genes integrated into viral (phages) genomes. After rising above the Darwinian threshold, rigid rules of speciation and vertical inheritance in the three domains of life were established, but horizontal gene transfers with or without cell fusions were never abolished. The author proves with extensive, yet highly selective documentation, that not only unicellular microorganisms, but the most complex multicellular entities of the highest ranks resort to, and practice, cell fusions, and donate and accept horizontally (laterally) transferred genes. Cell fusions and horizontally exchanged genetic materials remain the fundamental attributes and inherent characteristics of the living matter, whether occurring accidentally or sought after intentionally. These events occur to cells stagnating for some 3 milliard years at a lower yet amazingly sophisticated level of evolution, and to cells achieving the highest degree of differentiation, and thus functioning in dependence on the support of a most advanced multicellular host, like those of the human brain. No living cell is completely exempt from gene drains or gene insertions.


title: Evaluation on the antiviral activity of arctigenin against spring viraemia of carp virus

text: Abstract Spring viraemia of carp virus (SVCV) causes high morality in several economically important cyprinid fishes, but there is no approved therapy up to now. To address the urgent need for therapeutics to combat SVCV infection, we investigated the anti-SVCV activities of 12 natural compounds and 7 common antiviral agents using epithelioma papulosum cyprini (EPC) cells in this study. From the 19 compounds, we identified arctigenin (ARG) has the highest inhibition on SVCV replication, with maximum inhibitory percentage on SVCV>90%. And the 48h half maximal inhibitory concentrations (IC50) of ARG on SVCV glycoprotein and nucleoprotein were 0.29 (0.22–0.39) and 0.35 (0.29–0.41)mg/L respectively. In addition, ARG significantly reduced SVCV-induced apoptosis and recovered SVCV-activated caspase-3/8/9 activity. Further, cellular morphological damage induced by SVCV was blocked by ARG treatment. Mechanistically, ARG did not affect SVCV infectivity. Moreover, ARG could not induce reactive oxygen species (ROS) generation, which plays an antiviral role on SVCV. Interestingly, SVCV-induced autophagy which is necessary for virus replication was inhibited by ARG treatment. These results indicated that the inhibition of ARG on SVCV replication was, at least in part, via blocking SVCV-induced autophagy. Taken together, ARG has the potential to work as an agent for protecting economically important fishes against SVCV.


title: Nursing of critically ill COVID-19 patients treated with extracorporeal membrane oxygenation

text: OBJECTIVE: This study attempted to explore nursing methods as well as extracorporeal membrane oxygenation (ECMO) therapy in the treatment of critically ill COVID-19 patients. It can be used for reference by nursing colleagues to improve the treatment success rate of critically ill patients with COVID-19 treated with ECMO and reduce the mortality rate. METHODS: The clinical data of three critically ill COVID-19 patients who underwent ECMO therapy and their nursing measures were retrospectively analyzed. RESULTS: Two patients were successfully removed from ECMO while one patient died. CONCLUSION: Severe COVID-19 is a highly contagious disease with a high case fatality rate. Strict prevention, timely observation, effective management of complications and smooth running of ECMO are key ways in successfully treating critically ill COVID-19 patients.


The COVID-19 Diagnostic Technology Landscape: Efficient Data Sharing Drives Diagnostic Development


title: Steroid-induced osteonecrosis in severe acute respiratory syndrome: a retrospective analysis of biochemical markers of bone metabolism and corticosteroid therapy

text: Summary Aim We investigated the effect of massive doses of corticosteroid therapy on bone metabolism using specific biochemical markers of bone metabolism, and the prevalence of osteonecrosis in severe acute respiratory syndrome (SARS) patients at a university teaching hospital in Hong Kong. Methods Seventy-one patients with a clinical diagnosis of SARS were studied according to the modified World Health Organization case definition of SARS who were involved in the SARS epidemic between 10 March and 20 June 2003. The clinical diagnosis was confirmed by serological test and/ or molecular analysis. Biochemical markers of bone metabolism were analysed retrospectively using serial clotted blood samples collected from each patient during the course of hospital admission to discharge and subsequent follow-up at out-patient clinic using the arbitrary time periods: (i) Day <10; (ii) Day 28-44; (iii) Day 51-84; and (iv) Day >90 after the onset of fever. Magnetic resonance imaging of the knee and hip joints were performed post-admission to evaluate the prevalence of osteonecrosis amongst these SARS patients. Various risk factors for the development of osteonecrosis were assessed using receiver operating characteristics curve comparison with appropriate test statistics and Spearman’s coefficients of rank correlation with biochemical bone markers. Results Biochemical markers of bone metabolism showed significant bone resorption as evidenced by a marked increase in serum C-terminal telopeptide concentration (CTx) from Day 28-44 after the onset of fever. With tapering down of corticosteroid dosage, CTx started to return to previous baseline level from Day 51 onwards, while other bone formation markers, serum osteocalcin and bone- specific alkaline phosphatase concentrations (OC and BALP, respectively), started to increase. The latter effect was even more marked after Day >90. Seven patients developed radiological evidence of osteonecrosis. The prevalence of osteonecrosis in this cohort was 9.9%. A total corticosteroid dosage of >1900mg hydrocortisone, >2000 mg methylprednisolone, >13 340 mg hydrocortisone-equivalent corticosteroid therapy, and >18 days on corticosteroid therapy were found to be significant risk factors for the subsequent development of osteonecrosis. There were also significant positive correlations amongst various biochemical bone markers in this patient cohort. Conclusion Both bone resorption and formation markers were unable to predict the subsequent development of osteonecrosis. The use of high dose of hydrocortisone or methylprednisolone for an extended duration was shown to be a significant risk factor for osteonecrosis. Its prevalence in this cohort is comparable to those reported in the literature for SARS patients with high-dose corticosteroid therapy. The Day 28–44 increase in the serum CTx coincided with the timing of corticosteroid use. The Day >51 increase in serum OC and BALP coincided with the timing of corticosteroid withdrawal.


title: Surface ultrastructure of SARS coronavirus revealed by atomic force microscopy

text: Atomic force microscopy has been used to probe the surface nanostructures of severe acute respiratory syndrome coronavirus (SARS‐CoV). Single crown‐like virion was directly visualized and quantitative measurements of the dimensions for the structural proteins were provided. A corona of large, distinctive spikes in the envelope was measured after treatment with hydroxyoctanoic acid. High‐resolution images revealed that the surface of each single SARS‐CoV was surrounded with at least 15 spherical spikes having a diameter of 7.29 ± 0.73 nm, which is in close agreement with that of S glycoproteins earlier predicted through the genomes of SARS‐CoV. This study represents the first direct characterization of the surface ultrastructures of SARS‐CoV particles at the nanometre scale and offers new prospects for mapping viral surface properties.


title: Bovine respiratory syncytial virus in experimentally exposed and rechallenged calves; viral shedding related to clinical signs and the potential for transmission

text: BACKGROUND: Bovine respiratory syncytial virus (BRSV) is an important respiratory pathogen worldwide, detrimentally affecting the economy and animal welfare. To prevent and control BRSV infection, further knowledge on virus shedding and transmission potential in individual animals is required. This study aimed to detect viral RNA and infective virions during BRSV infection to evaluate duration of the transmission period and correlation with clinical signs of disease. The outcome of BRSV re-exposure on calves, their housing environment and effect of introduction of sentinel calves was also investigated. A live animal experiment including 10 calves was conducted over 61 days. Initially, two calves were inoculated with a non-passaged BRSV field isolate. Two days later, six naïve calves (EG: Exposed group) were introduced for commingling and four weeks later, another two naïve calves (SG: Sentinel group) were introduced. Seven weeks after commingling, EG animals were re-inoculated. Clinical examination was performed daily. Nasal swabs were collected regularly and analysed for viral RNA by RT-ddPCR, while virus isolation was performed in cell culture. BRSV serology was performed with ELISA. RESULTS: All the EG calves seroconverted and showed clinical signs of respiratory disease. Viral RNA was detected from days 1–27 after exposure, while the infective virus was isolated on day 6 and 13. On day 19, all animals were seropositive and virus could not be isolated. Total clinical score for respiratory signs corresponded well with the shedding of viral RNA. The SG animals, introduced 27 days after exposure, remained negative for BRSV RNA and stayed seronegative throughout the study. Inoculation of the EG calves seven weeks after primary infection did not lead to new shedding of viral RNA or clinical signs of disease. CONCLUSION: Viral RNA was detected in nasal swabs from the calves up to four weeks after exposure. The detection and amount of viral RNA corresponded well with the degree of respiratory signs. The calves were shedding infective virions for a considerable shorter period, and naïve calves introduced after four weeks were not infected. Infected calves were protected from reinfection for at least seven weeks. This knowledge is useful to prevent spread of BRSV.


title: South Africa deploys hydrogen fuel cells at Pretoria hospital to support Covid-19 response

text: South Africa's Department of Science and Innovation (DSI), in partnership with the Department of Defence (DOD) and Department of Public Works and Infrastructure (DPWI), is deploying seven hydrogen fuel cell systems at 1 Military Hospital in the capital Pretoria, to assist with the government's response to the Covid-19 pandemic.


title: [63] Fatty acid acylation of eukaryotic cell proteins

text: Publisher Summary This chapter presents an overview of fatty acid acylation of eukaryotic cell proteins. The chapter describes the distribution of fatty acid acylated proteins, distribution of fatty acid acylated proteins, analysis of the fatty acid, and site and mechanism of fatty acid acylation. Many of the data pertaining to fatty acid acylation of eukaryotic cell membrane proteins come from studies with those glycoproteins that form the external spikes on enveloped RNA animal viruses. The procedures for detecting and identifying protein-bound fatty acids rely primarily on incorporating high specific radioactive labeled fatty acids into growing tissue culture cells and analyzing proteins from these cells by electrophoresis in sodium dodecyl sulfate (SDS)-polyacrylamide gels. The function of fatty acid in membrane proteins is unknown, and it is believed that fatty acid acylation might be important for proper intracellular transport of proteins destined to be localized to the plasma membrane.


title: Chapter 7 Herbal extracts as antiviral agents

text: Abstract Phytotherapy, or herbalism, is defined as the usage of plants or herbs as medication to treat or prevent diseases in human and animals. The usage is gaining more attention among medical practitioners as well as large-scale livestock producers. A number of reports have shown the positive effects of herbal extracts as an antiviral agent used in animal feed or as a prophylaxis and remedy. Besides being a cheaper and safer alternative, the use of herbs may reduce the incidence of drug resistance and may modulate the immune system in preventing viral-related diseases. In this chapter, the antiviral effects of several herbs and their extracts against viruses in terms of the mechanism of action in targeting viral replication steps, the effects in the host and the application in animals will be discussed. The information given may aid in improving the health and increase the production of animals.


title: Analysis of the lung microbiota in dogs with Bordetella bronchiseptica infection and correlation with culture and quantitative polymerase chain reaction

text: Infection with Bordetella bronchiseptica (Bb), a pathogen involved in canine infectious respiratory disease complex, can be confirmed using culture or qPCR. Studies about the canine lung microbiota (LM) are recent, sparse, and only one paper has been published in canine lung infection. In this study, we aimed to compare the LM between Bb infected and healthy dogs, and to correlate sequencing with culture and qPCR results. Twenty Bb infected dogs diagnosed either by qPCR and/or culture and 4 healthy dogs were included. qPCR for Mycoplasma cynos (Mc) were also available in 18 diseased and all healthy dogs. Sequencing results, obtained from bronchoalveolar lavage fluid after DNA extraction, PCR targeting the V1–V3 region of the 16S rDNA and sequencing, showed the presence of Bb in all diseased dogs, about half being co-infected with Mc. In diseased compared with healthy dogs, the β-diversity changed (P = 0.0024); bacterial richness and α-diversity were lower (P = 0.012 and 0.0061), and bacterial load higher (P = 0.004). Bb qPCR classes and culture results correlated with the abundance of Bb (r = 0.71, P < 0.001 and r = 0.70, P = 0.0022). Mc qPCR classes also correlated with the abundance of Mc (r = 0.73, P < 0.001). Bb infection induced lung dysbiosis, characterized by high bacterial load, low richness and diversity and increased abundance of Bb, compared with healthy dogs. Sequencing results highly correlate with qPCR and culture results showing that sequencing can be reliable to identify microorganisms involved in lung infectious diseases.


title: Covid-19 exposure risk for family members of healthcare workers: an observational study

text: Abstract Background Many papers considered the exposure risk to COVID-19 of general population and healthcare workers (HW). However, no available papers discussed the risk of exposure of family members (FM) of HWs. Aims The present study collected the data of SARS-COV-2 positive FM of HWs using serological rapid IgM/IgG tests (SRT) compared with positive HWs at SRT and serological quantitative IgG test (SQT). Methods The study was conducted from 2nd to 31th May 2020. 38 HWs were tested by both SRT and SQT; 81 FMs were screened using SRT. Descriptive statistical analyses were used to summarize the data. Results Of the 38 HWs, 2 (5,3%) showed IgG line at SRT, confirmed by SQT. 32 HWs decided self-isolation from the family during SARS-COV-2 spreading. Out of 81 FMs, 26 (32,1%) were found IgG positive at SRT. 11 (42%) of them had symptoms typical for COVID-19 in the study period. In two families, the HWs were the only negative case. Conclusions General population’s exposure to COVID-19 was less controlled than HWs’ one. HWs experienced lower infection’s rate than their families and did not represented a risk of transmission for relatives.


docid: oprpgcyr

title: Impact of Severe Acute Respiratory Syndrome on Patient Access to Palliative Radiation Therapy

text: Abstract This study evaluated the impact of the severe acute respiratory syndrome (SARS) epidemic on access and utilization of palliative radiation therapy (RT) at a single institution using a retrospective chart review. A total of 649 patients seen between January and May 2002 and between January and May 2003 were evaluated. Treatment characteristics and waiting times were recorded. March 20 to May 30, 2003, was defined as the peak period of incidence and was compared with the same period in 2002. During the SARS epidemic, there was a 21% decrease in the number of patient consultations and a 15% reduction in the number of patients treated with RT. There was no significant change in the tumor type or reason for referral. Short fractionation schedules were employed for 35% of treated patients compared with 34% in 2002. Patient waiting times between referral and treatment decreased during the period of interest, from 16 days to 8 days (P = 0.021). This study demonstrates a reduction in palliative RT services that is similar in magnitude to decreases observed in other essential cancer services during the SARS epidemic. Use of single-fraction RT and delayed follow-up visits may help to minimize hospital transfers and visits in the event of future infectious disease outbreaks.


Some lessons from the COVID-19 pandemic virus


title: Structural genomics of infectious disease drug targets: the SSGCID

text: The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a consortium of researchers at Seattle BioMed, Emerald BioStructures, the University of Washington and Pacific Northwest National Laboratory that was established to apply structural genomics approaches to drug targets from infectious disease organisms. The SSGCID is currently funded over a five-year period by the National Institute of Allergy and Infectious Diseases (NIAID) to determine the three-dimensional structures of 400 proteins from a variety of Category A, B and C pathogens. Target selection engages the infectious disease research and drug-therapy communities to identify drug targets, essential enzymes, virulence factors and vaccine candidates of biomedical relevance to combat infectious diseases. The protein-expression systems, purified proteins, ligand screens and three-dimensional structures produced by SSGCID constitute a valuable resource for drug-discovery research, all of which is made freely available to the greater scientific community. This issue of Acta Crystallographica Section F, entirely devoted to the work of the SSGCID, covers the details of the high-throughput pipeline and presents a series of structures from a broad array of pathogenic organisms. Here, a background is provided on the structural genomics of infectious disease, the essential components of the SSGCID pipeline are discussed and a survey of progress to date is presented.


title: Chapter Four Next-Generation Molecular-Diagnostic Tools for Gastrointestinal Nematodes of Livestock, with an Emphasis on Small Ruminants A Turning Point?

text: Abstract Parasitic nematodes of livestock have major economic impact worldwide. Despite the diseases caused by these nematodes, some advances towards the development of new therapeutic agents and attempts to develop effective vaccines against some of them, there has been limited progress in the development of practical diagnostic methods. The specific and sensitive diagnosis of parasitic nematode infections of livestock underpins effective disease control, which is now particularly important given the problems associated with anthelmintic resistance in parasite populations. Traditional diagnostic methods have major limitations, in terms of sensitivity and specificity. This chapter provides an account of the significance of parasitic nematodes (order Strongylida), reviews conventional diagnostic techniques that are presently used routinely and describes advances in polymerase chain reaction (PCR)-based methods for the specific diagnosis of nematode infections. A particular emphasis is placed on the recent development of a robotic PCR-based platform for high-throughput diagnosis, and its significance and implications for epidemiological investigations and for use in control programmes.


title: Review of plasmonic fiber optic biochemical sensors: improving the limit of detection

text: This paper presents a brief overview of the technologies used to implement surface plasmon resonance (SPR) effects into fiber-optic sensors for chemical and biochemical applications and a survey of results reported over the last ten years. The performance indicators that are relevant for such systems, such as refractometric sensitivity, operating wavelength, and figure of merit (FOM), are discussed and listed in table form. A list of experimental results with reported limits of detection (LOD) for proteins, toxins, viruses, DNA, bacteria, glucose, and various chemicals is also provided for the same time period. Configurations discussed include fiber-optic analogues of the Kretschmann–Raether prism SPR platforms, made from geometry-modified multimode and single-mode optical fibers (unclad, side-polished, tapered, and U-shaped), long period fiber gratings (LPFG), tilted fiber Bragg gratings (TFBG), and specialty fibers (plastic or polymer, microstructured, and photonic crystal fibers). Configurations involving the excitation of surface plasmon polaritons (SPP) on continuous thin metal layers as well as those involving localized SPR (LSPR) phenomena in nanoparticle metal coatings of gold, silver, and other metals at visible and near-infrared wavelengths are described and compared quantitatively. [Figure: see text]


title: Role of viral and bacterial pathogens in causing pneumonia among Western Australian children: a case–control study protocol

text: INTRODUCTION: Pneumonia is the leading cause of childhood morbidity and mortality globally. Introduction of the conjugate Haemophilus influenzae B and multivalent pneumococcal vaccines in developed countries including Australia has significantly reduced the overall burden of bacterial pneumonia. With the availability of molecular diagnostics, viruses are frequently detected in children with pneumonia either as primary pathogens or predispose to secondary bacterial infection. Many respiratory pathogens that are known to cause pneumonia are also identified in asymptomatic children, so the true contribution of these pathogens to childhood community-acquired pneumonia (CAP) remains unclear. Since the introduction of pneumococcal vaccines, very few comprehensive studies from developed countries have attempted to determine the bacterial and viral aetiology of pneumonia. We aim to determine the contribution of bacteria and viruses to childhood CAP to inform further development of effective diagnosis, treatment and preventive strategies. METHODS AND ANALYSIS: We are conducting a prospective case–control study (PneumoWA) where cases are children with radiologically confirmed pneumonia admitted to Princess Margaret Hospital for Children (PMH) and controls are healthy children identified from PMH outpatient clinics and from local community immunisation clinics. The case–control ratio is 1:1 with 250 children to be recruited in each arm. Nasopharyngeal swabs are collected from both cases and controls to detect the presence of viruses and bacteria by PCR; pathogen load will be assessed by quantitative PCR. The prevalence of pathogens detected in cases and controls will be compared, the OR of detection and population attributable fraction to CAP for each pathogen will be determined; relationships between pathogen load and disease status and severity will be explored. ETHICS AND DISSEMINATION: This study has been approved by the human research ethics committees of PMH, Perth, Australia (PMH HREC REF 2014117EP). Findings will be disseminated at research conferences and in peer-reviewed journals.


title: Severe Acute Respiratory Syndrome Coronavirus Envelope Protein Ion Channel Activity Promotes Virus Fitness and Pathogenesis

text: Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na(+)/K(+) ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence.


docid: wkkrhmbr

title: Differential modulation of avian β-defensin and Toll-like receptor expression in chickens infected with infectious bronchitis virus

text: The host innate immune response either clears invading viruses or allows the adaptive immune system to establish an effective antiviral response. In this study, both pathogenic (passage 3, P3) and attenuated (P110) infectious bronchitis virus (IBV) strains were used to study the immune responses of chicken to IBV infection. Expression of avian β-defensins (AvBDs) and Toll-like receptors (TLRs) in 16 tissues of chicken were compared at 7 days PI. The results showed that P3 infection upregulated the expression of AvBDs, including AvBD2, 4, 5, 6, 9, and 12, while P110 infection downregulated the expression of AvBDs, including AvBD3, 4, 5, 6, and 9 in most tissues. Meanwhile, the expression level of several TLRs showed a general trend of upregulation in the tissues of P3-infected chickens, while they were downregulated in the tissues of P110-infected chickens. The result suggested that compared with the P110 strain, the P3 strain induced a more pronounced host innate immune response. Furthermore, we observed that recombinant AvBDs (including 2, 6, and 12) demonstrated obvious anti-viral activity against IBV in vitro. Our findings contribute to the proposal that IBV infection induces an increase in the messenger RNA (mRNA) expression of some AvBDs and TLRs, which suggests that AvBDs may play significant roles in the resistance of chickens to IBV replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00253-015-6786-8) contains supplementary material, which is available to authorized users.


title: Development of Rapid and Specific Detection for the Human Aichivirus A Using the Loop-Mediated Isothermal Amplification from Water Samples

text: Human Aichivirus A (AiV-A) is classified as a Kobuvirus, group IV positive sense single strand RNA viruses. The first outbreak of AiV-A was reported from Aichi Prefecture, Japan in 1989. AiV-A exists not only among clinical patients, such as diarrhea, but also in a variety of water environments, as its occurrence is reported across a wide geographical range, from developing to advanced countries. For diagnose of AiV-A from water samples, mostly polymerase chain reaction (PCR) system have been developed. However, loop-mediated isothermal amplification (LAMP) assay has not been applied. In this study, developed a LAMP method to achieve a rapid, specific and highly sensitive detection of AiV-A. The method developed in this study is aimed specifically at AiV-A. Through a specific and non-specific selection and sensitivity test process for the five prepared LAMP primer sets, one primer set and optimum reaction temperature were selected. A newly developed method was more rapid (approximately 2–8 h), specific and equivalent detection of AiV-A than with the conventional PCRs. In addition, confirm system of positive LAMP reaction was developed by using the restriction enzyme Aci I and Hae III. For evaluation and verification of developing LAMP assay, a was applied to twenty cDNA from groundwater samples. This study proved rapid and specific diagnosis of AiV-A from water samples, and it is also demanded to be applicable to other environmental, clinical and food samples. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12088-019-00803-3) contains supplementary material, which is available to authorized users.


title: Enhanced platelet inhibition treatment improves hypoxemia in patients with severe Covid-19 and hypercoagulability. A case control, proof of concept study

text: Patients affected by severe coronavirus induced disease-2019 (Covid-19) often experience hypoxemia due to alveolar involvement and endothelial dysfunction, which leads to the formation of micro thrombi in the pulmonary capillary vessels. Both hypoxemia and a prothrombotic diathesis have been associated with more severe disease and increased risk of death. To date, specific indications to treat this condition are lacking. This was a single center, investigator initiated, compassionate use, proof of concept, case control, phase IIb study (NCT04368377) conducted in the Intermediate Respiratory Care Unit of L. Sacco University Hospital in Milano, Italy. Our objective was to explore the effects of the administration of anti-platelet therapy on arterial oxygenation and clinical outcomes in patients with severe Covid-19 with hypercoagulability. We enrolled five consecutive patients with laboratory confirmed SARS-CoV-2 infection, severe respiratory failure requiring helmet continuous positive airway pressure (CPAP), bilateral pulmonary infiltrates and a pro-thrombotic state identified as a D-dimer > 3 times the upper limit of normal. Five patients matched for age, D-dimer value and SOFA score formed the control group. Beyond standard of care, treated patients received 25 µg/Kg/body weight tirofiban as bolus infusion, followed by a continuous infusion of 0.15 µg/Kg/body weight per minute for 48 hours. Before tirofiban, patients received acetylsalicylic acid 250 mg infusion and oral clopidogrel 300 mg; both were continued at a dose of 75 mg daily for 30 days. Fondaparinux2.5 mg/day sub-cutaneous was given for the duration of the hospital stay. All controls were receiving prophylactic or therapeutic dose heparin, according to local standard operating procedures. Treated patients consistently experienced a mean (SD) reduction in A-a O2 gradient of -32.6 mmHg (61.9, P = 0.154), -52.4 mmHg (59.4, P = 0.016) and -151.1 mmHg (56.6, P = 0.011; P = 0.047 vs. controls) at 24, 48 hours and 7 days after treatment. PaO2/FiO2 ratio increased by 52 mmHg (50, P = 0.172), 64 mmHg (47, P = 0.040) and 112 mmHg (51, P = 0.036) after 24, 48 hours and 7 days, respectively. All patients but one were successfully weaned from CPAP after 3 days. This was not true for the control group. No major adverse events were observed. Antiplatelet therapy might be effective in improving the ventilation/perfusion ratio in Covid-19 patients with severe respiratory failure. The effects might be sustained by the prevention and interference on forming clots in lung capillary vessels and by modulating megakaryocytes’ function and platelet adhesion. Randomized clinical trials are urgently needed to confirm these results.


title: Reactivation of COVID‐19 – 14 days from the onset of symptoms may not be enough to allow dental treatment

text: The pandemic of coronavirus disease 2019 (COVID‐19) has become a global health disaster (Phelan et al., 2020). On the level of dental practice, the risk of cross infection between infected patients and dental professionals is quite alarming. The current recommendations suggest that dental treatment of patients with suspected/confirmed coronavirus disease should be postponed for at least 14 days from the onset of symptoms (Peng et al., 2020).


title: Emerging biomedical applications of synthetic biology

text: Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications.


title: Sequence analysis of the bovine coronavirus nucleocapsid and matrix protein genes

text: Abstract The 3′ end of the 20-kb genome of the Mebus strain of bovine enteric coronavirus (BCV) was copied into cDNA and cloned into the PstI site of the pUC9 vector. Four clones from the 3′ end of the genome were sequenced either completely or in part to determine the sequence of the first 2451 bases. Within this sequence were identified, in order, a 3′-noncoding region of 291 bases, the gene for a 448-amino acid nucleocapsid protein (N) having a molecular weight of 49,379, and the gene for a 230-amino acid matrix protein (M) having a molecular weight of 26,376. A third large open reading frame is contained entirely within the N gene sequence but is positioned in a different reading frame; it potentially encodes a polypeptide of 207 amino acids having a molecular weight of 23,057. A higher degree of amino acid sequence homology was found between the M proteins of BCV and MHV (87%) than between the N proteins (70%). For the M proteins of BCV and MHV, notable differences were found at the amino terminus, the most probable site of O-glycosylation, where the sequence is N-Met-Ser-Ser-Val-Thr-Thr for BCV and N-Met-Ser-Ser-Thr-Thr for MHV. BCV apparently uses two of its six potential O-glycosylation sites.


title: Mathematical modeling and the transmission dynamics in predicting the Covid-19 - What next in combating the pandemic

text: Mathematical predictions in combating the epidemics are yet to reach its perfection. The rapid spread, the ways, and the procedures involved in containment of a pandemic demand the earliest understanding in finding solutions in line with the habitual, physiological, biological, and environmental aspects of life with better computerised mathematical modeling and predictions. Epidemiology models are key tools in public health management programs despite having a high level of uncertainty in each one of these models. This paper describes the outcome and the challenges of SIR, SEIR, SEIRU, SIRD, SLIAR, ARIMA, SIDARTHE, etc models used in prediction of spread, peak, and reduction of Covid-19 cases.


docid: fqxjzavm

title: Detection of coronavirus genomes in Moluccan naked-backed fruit bats in Indonesia

text: Bats have been shown to serve as natural reservoirs for numerous emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV). In the present study, we report the discovery of bat CoV genes in Indonesian Moluccan naked-backed fruit bats (Dobsonia moluccensis). A partial RNA-dependent RNA polymerase gene sequence was detected in feces and tissues samples from the fruit bats, and the region between the RdRp and helicase genes could also be amplified from fecal samples. Phylogenetic analysis suggested that these bat CoVs are related to members of the genus Betacoronavirus.


title: Safety and efficacy of early high-dose IV anakinra in severe COVID-19 lung disease

text: Cytokine release syndrome plays a crucial pathogenic role in COVID-19 pneumonia. This pilot study provides the first evidence of the safety of anti-IL-1 treatment with highdose IV anakinra in 5 patients, who experienced a positive outcome.


title: iTRAQ-based high-throughput proteomics analysis reveals alterations of plasma proteins in patients infected with human bocavirus

text: Human bocavirus (HBoV) is a member of the genus Bocavirus, family Parvoviridae, and subfamily Parvovirus and was first identified in nasopharyngeal aspirates of Swedish children with acute respiratory tract infection (ARTI) in 2005. It is the causative agent of nasopharyngeal aspirate disease and death in children. The HboV genomic structure is a linear single-stranded DNA (ssDNA). Its clinical pathogenic characteristics have been extensively studied, however, at present the molecular mechanism underlying the pathogenesis of HBoV infection is not completely clear. In this study, a total of 293 differentially expressed proteins (DEPs) between ARTI cases and healthy plasma samples were characterized using isobaric tags for relative and absolute quantitation (iTRAQ)-coupled bioinformatics analysis, among which 148 were up-regulated and 135 were down-regulated. Gene Ontology (GO) and Cluster of Orthologous Groups of proteins (COG) annotated an enrichment of DEPs in complement activation and biological processes like immunity, inflammation, signal transduction, substance synthesis, and metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis enriched DEPs mainly in the Wnt signaling pathway (ko04310), PPAR signaling pathway (ko03320), intestinal immune network for IgA production (ko04672), complement and coagulation cascades (ko04610), Toll-like receptor signaling pathway (ko04620) and B cell receptor signaling pathway (ko04662). Further, expression levels of three candidate proteins (upregulated PPP2R1A and CUL1, and downregulated CETP) were validated using western blotting. Our investigation is the first analysis of the proteomic profile of HBoV-infected ARTI cases using the iTRAQ approach, providing a foundation for a better molecular understanding of the pathogenesis of ARTI in children.


title: Structure of the RNA-dependent RNA polymerase from COVID-19 virus

text: A novel coronavirus (COVID-19 virus) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12) is the central component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. We report the cryo-EM structure of COVID-19 virus full-length nsp12 in complex with cofactors nsp7 and nsp8 at 2.9-Å resolution. In addition to the conserved architecture of the polymerase core of the viral polymerase family, nsp12 possesses a newly identified β-hairpin domain at its N terminus. A comparative analysis model shows how remdesivir binds to this polymerase. The structure provides a basis for the design of new antiviral therapeutics targeting viral RdRp.


title: Evolução de indicadores e capacidade de atendimento no início da epidemia de COVID-19 no Nordeste do Brasil, 2020/ Evolución de los indicadores y capacidad de atención al comienzo de la epidemia de COVID-19 en el Nordeste de Brasil, 2020/ Evolution of indicators and service capacity at the beginning of the COVID-19 epidemic in Northeast Brazil, 2020

text: Resumo Objetivo descrever a evolução dos indicadores e a capacidade de atendimento em saúde na fase inicial da epidemia de COVID-19 na região Nordeste do Brasil. Métodos estudo descritivo com base em boletins epidemiológicos sobre os casos de COVID-19, até 1º de abril de 2020, divulgados pelo Ministério da Saúde. Calcularam-se taxa de incidência, letalidade e número de casos diários acumulados. Resultados foram identificados 1.005 casos confirmados de COVID-19, a maioria deles no Ceará e na Bahia. A taxa de incidência foi de 1,8/100 mil habitantes, e a letalidade, de 2,7%. O Ceará foi o estado com maior número de casos - em média, 29,6 casos novos por dia. A média de oferta de leitos de terapia intensiva na região Nordeste (1,04/10 mil hab.) encontrava-se abaixo da média nacional (2,8/10 mil hab.). Conclusão os indicadores sugerem a heterogeneidade do impacto da COVID-19 e sinalizam os desafios para os sistemas de saúde da região Nordeste.(AU)


title: SARS-CoV Antibody Prevalence in All Hong Kong Patient Contacts

text: A total of 1,068 asymptomatic close contacts of patients with severe acute respiratory (SARS) from the 2003 epidemic in Hong Kong were serologically tested, and 2 (0.19%) were positive for SARS coronavirus immunoglobulin G antibody. SARS rarely manifests as a subclinical infection, and at present, wild animal species are the only important natural reservoirs of the virus.


title: Detection of enterotoxigenic K99 (F5) and F41 from fecal sample of calves by molecular and serological methods

text: Enterotoxigenic Escherichia coli (ETEC) is one of the major causes of neonatal calf diarrhea. Almost all ETEC bacteria are known to adhere to receptors on the small intestinal epithelium via their fimbriae, (F5 (K99) and F41).This study was undertaken to investigate the phenotypic and genotypic screening of virulence genes in E. coli K99 and F41. During January 2008 to December 2009, 298 diarrheic neonatal calves at 1–30 days old were studied by multiplex PCR, isolation, and serological grouping. Of the 298 diarrheic samples, 268 E. coli were isolated, of which 16 samples (5.3%) were positive for having the F5 (K99) fimbrial gene by PCR while all of the E. coli isolates also carried F41 fimbrial genes. Twenty-five percent of the isolates were proven not to be toxigenic as they did not possess the STa enterotoxin gene.


title: Can long-term historical data from electronic medical records improve surveillance for epidemics of acute respiratory infections? A systematic evaluation

text: BACKGROUND: As the deployment of electronic medical records (EMR) expands, so is the availability of long-term datasets that could serve to enhance public health surveillance. We hypothesized that EMR-based surveillance systems that incorporate seasonality and other long-term trends would discover outbreaks of acute respiratory infections (ARI) sooner than systems that only consider the recent past. METHODS: We simulated surveillance systems aimed at discovering modeled influenza outbreaks injected into backgrounds of patients with ARI. Backgrounds of daily case counts were either synthesized or obtained by applying one of three previously validated ARI case-detection algorithms to authentic EMR entries. From the time of outbreak injection, detection statistics were applied daily on paired background+injection and background-only time series. The relationship between the detection delay (the time from injection to the first alarm uniquely found in the background+injection data) and the false-alarm rate (FAR) was determined by systematically varying the statistical alarm threshold. We compared this relationship for outbreak detection methods that utilized either 7 days (early aberrancy reporting system (EARS)) or 2–4 years of past data (seasonal autoregressive integrated moving average (SARIMA) time series modeling). RESULTS: In otherwise identical surveillance systems, SARIMA detected epidemics sooner than EARS at any FAR below 10%. The algorithms used to detect single ARI cases impacted both the feasibility and marginal benefits of SARIMA modeling. Under plausible real-world conditions, SARIMA could reduce detection delay by 5–16 days. It also was more sensitive at detecting the summer wave of the 2009 influenza pandemic. CONCLUSION: Time series modeling of long-term historical EMR data can reduce the time it takes to discover epidemics of ARI. Realistic surveillance simulations may prove invaluable to optimize system design and tuning.


title: Infectivity inhibition by overlapping synthetic peptides derived from the gH/gL heterodimer of herpes simplex virus type 1

text: Herpes simplex virus (HSV) is a human pathogen that infects epithelial cells. The cutaneous lesions, caused by the virus, spread to the nervous system creating several complications. Fusion of host membranes with the viral envelope is mandatory and mediated by a group of glycoproteins conserved in all Herpesviridae subfamilies, such as the glycoproteins B (gB), H (gH), L (gL) and D (gD). We investigated the inhibitory activity mediated by synthetic overlapping peptides spanning the entire ectodomains of gH and gL glycoproteins. We have performed a brute analysis of the complete gH/gL heterodimer in order to explore the inhibitory activity of peptides modelled on these glycoproteins against HSV‐1 infection. Twenty‐four of the gH peptides at a concentration of 150 μM reached the 50% of inhibition cut‐off. Interestingly, they are mainly located in the gH carboxy‐terminal domain. None of the gL peptides had a clear inhibiting effect. No peptide toxicity was observed by lactate dehydrogenase assay at the concentrations used in our experimental conditions. HSV‐1 therapy is based on acyclovir treatment, but some resistant strains are emerging. In this scenario, innovative approaches for HSV‐1 treatment are necessary. Our data support the direct involvement of the described domains in the process of virus penetration; therefore, these results are of relevance to the potential development of novel therapeutic compounds to prevent HSV‐1 infections. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.


Coronataxi brings outpatient care to covid-19 patients


title: Commentary on the Regulation of Viral Proteins in Autophagy Process

text: The ability to subvert intracellular antiviral defenses is necessary for virus to survive as its replication occurs only in the host cells. Viruses have to modulate cellular processes and antiviral mechanisms to their own advantage during the entire virus life cycle. Autophagy plays important roles in cell regulation. Its function is not only to catabolize aggregate proteins and damaged organelles for recycling but also to serve as innate immunity to remove intracellular pathogenic elements such as viruses. Nevertheless, some viruses have evolved to negatively regulate autophagy by inhibiting its formation. Even more, some viruses have employed autophagy to benefit their replication. To date, there are more and more growing evidences uncovering the functions of many viral proteins to regulate autophagy through different cellular pathways. In this review, we will discuss the relationship between viruses and autophagy and summarize the current knowledge on the functions of viral proteins contributing to affect autophagy process.


title: Longitudinal study of Middle East Respiratory Syndrome coronavirus infection in dromedary camel herds in Saudi Arabia, 2014–2015

text: Two herds of dromedary camels were longitudinally sampled with nasal and rectal swabs and serum, between September 2014 and May 2015, and the samples were tested for Middle East Respiratory Syndrome (MERS) coronavirus RNA and antibodies. Evidence of MERS-CoV infection was confirmed in one herd on the basis of detection of virus RNA in nasal swabs from three camels and significant increases in the antibody titers from three others. The three viruses were genetically identical, thus indicating introduction of a single virus into this herd. There was evidence of reinfection of camels that were previously seropositive, thus suggesting that prior infection does not provide complete immunity from reinfection, a finding that is relevant to camel vaccination strategies as a means to prevent zoonotic transmission.


docid: tyimwctm

title: Role of MIF Cytokine/CD74 Receptor Pathway in Protecting Against Injury and Promoting Repair

text: Wound healing after an injury is essential for life. An in-depth understanding of the healing process is necessary to ultimately improve the currently limited treatment options for patients suffering as a result of damage to various organs and tissues. Injuries, even the most minor, trigger an inflammatory response that protects the host and activates repair pathways. In recent years, substantial progress has been made in delineating the mechanisms by which inflammatory cytokines and their receptors facilitate tissue repair and regeneration. This mini review focuses on emerging literature on the role of the cytokine macrophage migration inhibitory factor (MIF) and its cell membrane receptor CD74, in protecting against injury and promoting healing in different parts of the body.


docid: tmdaddhe

title: Association of Human Metapneumovirus with Radiologically Diagnosed Community-Acquired Alveolar Pneumonia in Young Children

text: Objectives To determine the involvement of human metapneumovirus (HMPV) in childhood community-acquired alveolar pneumonia (CAAP) and compare the demographic, clinical, and laboratory features of HMPV-associated CAAP and CAAP associated with other respiratory viruses. Study design Nasopharyngeal wash specimens obtained prospectively over a 4-year period from children age < 5 years evaluated in the emergency department with radiologically diagnosed CAAP and from healthy controls were tested for HMPV by reverse-transcriptase polymerase chain reaction and for respiratory syncytial virus (RSV), adenovirus, influenza and parainfluenza viruses by direct immunofluorescence and culture. Results HMPV was detected in 108 of 1296 patients (8.3%) versus RSV in 23.1%, adenovirus in 3.4%, influenza A virus in 2.9%, and parainfluenza viruse in 2.9%. During the period of peak activity (November to May), HMPV was detected in 95 of 1017 patients (9.3%) and in 3 of 136 controls (2.2%) (P = .005). The patients with HMPV were older than those with RSV (P < .001) with a more common history of acute otitis media requiring tympanocentesis (P = .032), wheezing (P = .001) and gastrointestinal symptoms (P < .001) and a lower hospitalization rate (P = .005). Conclusions The high detection rate suggests an important role for HMPV in childhood CAAP. Our findings identify demographic and clinical features of HMPV-positive CAAP and its age-related impact on hospital admissions.


title: Desperate Times, Desperate Measures: The Case for RRx-001 in the Treatment of COVID-19

text: This article summarizes the likely attenuation properties of RRx-001 in COVID-19 based on its mechanism of action and the putative pathogenesis of the disease, which appears to activate inflammatory, oxidative and immune cascades with the potential to culminate in acute respiratory distress syndrome (ARDS), cytokine storm and death. An ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 appears to present with three major patterns of clinical symptomatology: 1) mild upper respiratory tract infection, 2) non-life-threatening pneumonia and 3) severe pneumonia and ARDS that initially manifest as a mild prodrome lasting for 7-8 days before rapid clinical and radiological deterioration requiring ICU transfer. RRx-001 is a targeted nitric oxide (NO) donor. This small molecule, which has been evaluated in multiple Phase 1 – 2 clinical trials for cancer as well as a Phase 3 clinical trial for the treatment of small cell lung cancer called REPLATINUM (NCT03699956), is minimally toxic and demonstrates clear evidence of anti-tumor activity. During the course of these clinical trials it was noted that the rate of chronic obstructive pulmonary disease (COPD) exacerbation and pneumonia in actively smoking SCLC patients treated with RRx-001 is less than 1%. Due to extensive history of tobacco use, 40-70% of patients with lung cancer have COPD(1) and the expected rate of pulmonary infection in this population is 50-70%,(2) which was not observed in RRx-001 clinical trials. Moreover, in preclinical studies of pulmonary hypertension, RRx-001 was found to be comparable with or more effective than the FDA approved agent, Bosentan. The potential pulmonary protective effects of RRx-001 in patients with recurrent lung infections coupled with preclinical models demonstrating RRx-001-mediated reversal of pulmonary hypertension suggests therapeutic activity in patients with acute respiratory symptoms due to COVID 19. Clinical trials have been initiated to confirm the hypothesis that RRx-001 may be repurposed to treat SARS-CoV-2 infection.


title: Entry of viruses through the epithelial barrier: pathogenic trickery

text: Mucosal surfaces — such as the lining of the gut or the reproductive tract — are the main point of entry for viruses into the body. As such, almost all viruses interact with epithelial cells, and make use of the normal epithelial signalling and trafficking pathways of the host cell. In addition to protein receptors, carbohydrate chains of proteoglycans and epithelial-membrane glycosphingolipids have emerged as a new class of receptors for viral attachment to the host cell.


COVID‐19 and Asthma, the Good or the Bad?


title: TOWARDS AN EVOLUTION OF INTERPROFESSIONAL PRACTICE: LESSONS LEARNED FROM TWO PIANO TRIOS()()

text: Interprofessional practice has been of great interest to both health systems and educational institutions, but has been slow to develop in actual practice. Important efforts to speed adoption have mostly focused on changes in structure or educational interventions. It turns out that the field of jazz music was grappling with similar issues in the early 1960s. In this essay, we draw lessons from the experiences of jazz musicians during a time of transition. We conclude that significant cultural transformation, focused on two paradoxes, and the barriers and contexts that flow from them, will be necessary to achieve ideal interprofessional healthcare practice.


title: Infecciones respiratorias en Urgencias

text: Resumen Las infecciones respiratorias suponen el 63,8% de las infecciones atendidas. De ellas, la cuarta parte son del tracto respiratorio inferior: bronquitis agudas, agudización de la EPOC o bronquiectasias y neumonía. Las bronquitis agudas suelen ser de etiología vírica y en pacientes inmunocompetentes y sin comorbilidad, el tratamiento es sintomático con analgésicos y antiinflamatorios. La principal causa de agudización de la EPOC es la infección respiratoria. La indicación de antibioterapia empírica y la elección de la misma se basa en criterios clínicos, la gravedad de la enfermedad de base, la gravedad de la agudización y la presencia de factores de riesgo para la infección por P. aeruginosa. La neumonía adquirida en la comunidad (NAC) es la principal causa de mortalidad de origen infeccioso. Se recomienda el uso de escalas pronósticas de gravedad (PSI o CURB-65) para decidir dónde se instaura el tratamiento, las pruebas a realizar para el diagnóstico etiológico y la antibioterapia empírica recomendada. Pacientes con neumonía relacionada con la asistencia sanitaria (NRAS) y neumonía nosocomial (NN) presentan mayor riesgo de infección por microorganismos multirresistentes (MMR) y mayor morbimortalidad. Requiere un tratamiento empírico específico en función de la gravedad de la enfermedad y los factores de riesgo presentes para la infección por MMR. Abstract Respiratory infections account for 63.8% of infections met. Of which a quarter are lower respiratory tract: acute bronchitis, exacerbation of COPD or bronchiectasis and pneumonia. Acute bronchitis usually of viral etiology and in immunocompetent patients without comorbidity treatment is symptomatic with analgesics and anti-inflammatories. The main cause of exacerbation of COPD is the respiratory infection. The indication of empirical antibiotic choice and it is based on clinical criteria, the severity of the underlying disease, the severity of the exacerbation and the presence of risk factors for infection with Pseudomonas aeruginosa. The community-acquired pneumonia (CAP) is the leading cause of death by infection. The use of prognostic severity scales (PSI or CURB-65) is recommended for deciding where treatment is started, the tests to be performed for the etiological diagnosis and the recommended empirical antibiotic therapy. Patients with Healthcare Associated Pneumonia (HCAP) and nosocomial pneumonia (NP) have a higher risk of infection by multiresistant microorganisms (MMR) and increased morbidity and mortality. It requires specific empirical treatment depending on the severity of disease and risk factors for infection MMR.


title: Avian Colibacillosis and Salmonellosis: A Closer Look at Epidemiology, Pathogenesis, Diagnosis, Control and Public Health Concerns

text: Avian colibacillosis and salmonellosis are considered to be the major bacterial diseases in the poultry industry world-wide. Colibacillosis and salmonellosis are the most common avian diseases that are communicable to humans. This article provides the vital information on the epidemiology, pathogenesis, diagnosis, control and public health concerns of avian colibacillosis and salmonellosis. A better understanding of the information addressed in this review article will assist the poultry researchers and the poultry industry in continuing to make progress in reducing and eliminating avian colibacillosis and salmonellosis from the poultry flocks, thereby reducing potential hazards to the public health posed by these bacterial diseases.


Klinische Ethik: Onkologie in der Pandemie


title: Necrotiserende enterocolitis: samenvatting van de huidige kennis

text: Necrotizing enterocolitis (nec) is a very serious illness of the intestinal tract. The incidence of nec in a neonatal intensive care unit varies from 1 to 5%. Although the etiology is still not known, evidence suggests a multifactorial cause of the disease in which activated inflammatory mediators finally cause inflammation and necrosis of the bowel. Platelet activating factor (paf) is supposed to be one of the most important mediators. The primary risk factor for nec is prematurity. Other factors include infection, bowel ischemia and exposition of the premature bowel to enteral feedings. nec is mostly seen in extremely prematures and prematures with growth retardation (birthweight less than 10th percentile). nec is known for its serious course. About 30% of the patients die during the course of the disease. Different strategies to prevent nec are still unsatisfactory to eliminate nec. In the future, more understanding is expected to come from extended knowledge of the role of inflammatory mediators.


title: Seroepidemiology of group I human coronaviruses in children

text: BACKGROUND: Recently, several new human coronaviruses have been identified. OBJECTIVES: To define the seroepidemiology of group I human coronaviruses STUDY DESIGN: A recombinant protein enzyme linked immunosorbent assay (ELISA) based on portions of the nucleocapsid protein of group I human coronaviruses was developed and was used to screen serum from 243 children and young adults. RESULTS: For HCoV-229E, the percentages of seropositive individuals were 57.1% for infants < 2 months old; 38.9% for infants 2–3 months old; 4.7% for infants 4–5 months old; 42.9–50.0% for infants 6–12 months old; and 34.8–62.5% for individuals 1–20 years old. For HCoV-NL63, the percentages of seropositive individuals were 45.2% for infants < 2 months old; 11.1% for infants 2–3 months old; 4.7% for infants 4–5 months old; 28.6–40.0% for infants 6–12 months old; and 25.0–70.3% for individuals 1–20 years old. CONCLUSIONS: Infection with these viruses is common in childhood though the prevalence of these viruses may vary from year to year.


title: Molecular Approaches to Recognize Relevant and Emerging Infectious Diseases in Animals

text: Since the introduction of the first molecular tests, there has been a continuous effort to develop new and improved assays for rapid and efficient detection of infectious agents. This has been motivated by a need for improved sensitivity as well as results that can be easily communicated. The experiences and knowledge gained at the World Organisation for Animal Health (OIE) Collaborating Centre for Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine, Uppsala, Sweden, will here be used to provide an overview of the different molecular approaches that can be used to diagnose and identify relevant and emerging infectious diseases in animals.


title: Multiple Fatalities in a Family Cluster of COVID-19 With Acute Respiratory Distress Syndrome

text: Background: Cases of COVID-19 family clusters have been reported across the globe. While disease severity can vary widely, reports of severe infection leading to multiple fatalities within a family are limited. Case Report: Four family members each presented to the emergency department with fever and upper respiratory symptoms. Each individual tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection via nasopharyngeal swab. All individuals developed acute respiratory distress syndrome refractory to conventional medical therapy and subsequently died from their disease. Conclusion: This report describes a familial cluster of fatal COVID-19 infections and suggests a potential genetic predisposition for severe disease, emphasizing the importance of investigating family clusters of severe COVID-19 infection to determine host and viral factors that may predispose to a severe disease course. Such investigations could improve our understanding of the disease and guide preventive measures for at-risk populations.


title: A neutralization assay for chikungunya virus infections in a multiplex format

text: Abstract Chikungunya virus (CHIKV) is a mosquito-transmitted Alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever and severe arthritis that can persist for years. Since the epidemic on La Réunion in 2006, CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions of the eastern and western hemispheres, including Europe and the United States. A. albopictus might continue migrating north with continuing climate change and CHIKV would then no longer be confined to the developing nations. No treatment or licensed CHIKV vaccine exists. A CHIKV neutralization assay in a 384-well format by using CHIKV-pseudotyped lentiviral vectors was established. This assay system can be used for entry inhibitor screening under a reduced safety level (S2). Production of CHIKV-pseudotyped lentiviral vectors and the reaction volume are optimized. A dose dependent, specific neutralization of CHIKV-pseudotyped vectors with sera of CHIKV-infected individuals could be measured in a 384-well format. A safe and simple multiplex assay for the analysis of CHIKV neutralizing activities was developed and will be able to improve drug and vaccine development as well as it would improve the understanding of CHIKV epidemics regarding antibody responses.


title: CFD simulation of the effect of an upstream building on the inter-unit dispersion in a multi-story building in two wind directions

text: Abstract Previous studies on inter-unit dispersion are limited to isolated buildings. The influence of an upstream interfering building may significantly modify the indoor airflow characteristics of the wind-induced natural ventilated downstream interfered building. Motivated by the findings in previous studies, namely that infectious respiratory aerosols exhausted from a unit can re-enter into another unit in the same building through building envelope openings, this study investigates the inter-unit pollutant dispersion around a multi-story building in two wind directions by employing the computational fluid dynamics (CFD) method. The CFD model employed in this study has been validated against previous experimental data. The results show that the presence of an upstream building greatly changes the path lines around the downstream target building and the pollutant transportation routes around it. The presence of a low upstream building also greatly increases the average air exchange rate (ACH) values and the pollutant re-entry ratios (R k ) below the source unit on the windward side of the downstream target building for normal wind incidence. However, the presence of a high upstream building greatly increases the average ACH values on the windward side and increases the R k on the leeward side of the downstream building for oblique wind incidence.


title: Role of genomic and proteomic tools in the study of host–virus interactions and virus evolution

text: Viruses have short replication cycles and produce genomic variants within a host, a process that seems to adapt to their specific host and also enable them to infect new hosts. The recent emergence of viral genomic variants from the circulating pool within the host population and re-emergence of the old ones are posing serious threat to agriculture, animal husbandry and humanity as a whole. This review assesses the potential role of genomic and proteomic tools that can monitor not only the course of infection and pathogenesis, but also predict the pandemic or zoonotic epidemic potential of a virus in a previously exposed or immunologically naive biological population.


title: Worried Well and Covid-19: Re-emergence of an old quandary

text: • 'Worried Well', as a concept, was first described during HIV; • Current COVID-19 Pandemic has given rise to wave of worried well again; • This leads to burden on already overburdened health care system. • Having good “surge capacity”, “mild casualty centres” and effective triage of cases are the solutions.


The impact of implicit bias in the pandemic age: Protecting our pediatric patients


title: Evaluation of a novel vesicular stomatitis virus pseudotype‐based assay for detection of neutralizing antibody responses to SARS‐CoV

text: Severe acute respiratory syndrome (SARS)‐coronavirus (SARS‐CoV) is the causative agent of SARS. The S protein of SARS‐CoV is a major target for neutralizing antibodies (Nabs) in infected patients. We developed a neutralization assay using a recombinant vesicular stomatitis virus (VSV) bearing SARS‐CoV‐S protein (VSV‐SARS‐St19). A total of 56 serum samples collected from 22 healthcare workers in the Hanoi French Hospital during the SARS epidemic in 2003 were evaluated and compared to the conventional neutralizing assay using infectious SARS‐CoV. The results of the neutralization assay using VSV‐SARS‐St19 pseudotype showed good correlations with those using infectious SARS‐CoV. The newly developed neutralization assay was more sensitive to low antibody titers in serum samples. Thus, the VSV‐SARS‐St19 is a useful tool for detecting Nabs against SARS‐CoV. J. Med. Virol. 78:1509–1512, 2006. © 2006 Wiley‐Liss, Inc.


title: Medical Students and Pandemic Influenza

text: To assess knowledge of pandemic influenza, we administered a questionnaire to all medical students at the University of Alberta; 354 (69%) of 510 students responded. Data from questionnaires such as this could help determine the role of medical students during a public health emergency.


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title: Thoughts on the origins, present, and future of the coronavirus crisis: marginalization, food and housing, and grassroots strategies


title: Going remote: Maintaining normalcy in our pathology laboratories during the COVID‐19 pandemic

text: To minimize disruptions to the practice of academic pathology, one can leverage modern information and communication technologies to create virtual connections. The overall sentiment after switching to a predominantly remote environment has been overwhelmingly positive, and this presents a novel opportunity to explore additional digital workflows.


Aneurysmal Subarachnoid Hemorrhage: Collateral Damage of COVID?


title: Inhibitory effect of small interfering RNA on dengue virus replication in mosquito cells

text: BACKGROUND: Dengue viruses (DENs) are the wildest transmitted mosquito-borne pathogens throughout tropical and sub-tropical regions worldwide. Infection with DENs can cause severe flu-like illness and potentially fatal hemorrhagic fever. Although RNA interference triggered by long-length dsRNA was considered a potent antiviral pathway in the mosquito, only limited studies of the value of small interfering RNA (siRNA) have been conducted. RESULTS: A 21 nt siRNA targeting the membrane glycoprotein precursor gene of DEN-1 was synthesized and transfected into mosquito C6/36 cells followed by challenge with DEN. The stability of the siRNA in cells was monitored by flow cytometry. The antiviral effect of siRNA was evaluated by measurement of cell survival rate using the MTT method and viral RNA was quantitated with real-time RT-PCR. The presence of cells containing siRNA at 0.25, 1, 3, 5, 7 days after transfection were 66.0%, 52.1%, 32.0%, 13.5% and 8.9%, respectively. After 7 days incubation with DEN, there was reduced cytopathic effect, increased cell survival rate (76.9 ± 4.5% vs 23.6 ± 14.6%) and reduced viral RNA copies (Ct value 19.91 ± 0.63 vs 14.56 ± 0.39) detected in transfected C6/36 cells. CONCLUSIONS: Our data showed that synthetic siRNA against the DEN-1 membrane glycoprotein precursor gene effectively inhibited DEN-1 viral RNA replication and increased C6/36 cell survival rate. siRNA may offer a potential new strategy for prevention and treatment of DEN infection.


title: Does this patient have COVID-19? A practical guide for the internist

text: Coronavirus disease 2019 (COVID-19) is currently causing a pandemic and will likely persist in endemic form in the foreseeable future. Physicians need to correctly approach this new disease, often representing a challenge in terms of differential diagnosis. Although COVID-19 lacks specific signs and symptoms, we believe internists should develop specific skills to recognize the disease, learning its ‘semeiotic’. In this review article, we summarize the key clinical features that may guide in differentiating a COVID-19 case, requiring specific testing, from upper respiratory and/or influenza-like illnesses of other aetiology. We consider two different clinical settings, where availability of the different diagnostic strategies differs widely: outpatient and inpatient. Our reasoning highlights how challenging a balanced approach to a patient with fever and flu-like symptoms can be. At present, clinical workup of COVID-19 remains a hard task to accomplish. However, knowledge of the natural history of the disease may aid the internist in putting common and unspecific symptoms into the correct clinical context.


title: Factors influencing integration of TB services in general hospitals in two regions of China: a qualitative study

text: BACKGROUND: In the majority of China, the Centre for Disease Control (CDC) at the county level provides both clinical and public health care for TB cases, with hospitals and other health facilities referring suspected TB cases to the CDC. In recent years, an integrated model has emerged, where the CDC remains the basic management unit for TB control, while a general hospital is designated to provide clinical care for TB patients. This study aims to explore the factors that influence the integration of TB services in general hospitals and generate knowledge to aid the scale-up of integration of TB services in China. METHODS: This study adopted a qualitative approach using interviews from sites in East and West China. Analysis was conducted using a thematic framework approach. RESULTS: The more prosperous site in East China was more coordinated and thus had a better method of resource allocation and more patient-orientated service, compared with the poorer site in the West. The development of public health organizations appeared to influence how effectively integration occurred. An understanding from staff that hospitals had better capacity to treat TB patients than CDCs was a strong rationale for integration. However, the economic and political interests might act as a barrier to effective integration. Both sites shared the same challenges of attracting and retaining a skilled workforce for the TB services. The role of the health bureau was more directive in the Western site, while a more participatory and collaborative approach was adopted in the Eastern site. CONCLUSION: The process of integration identifies similarities and differences between sites in more affluent East China and poorer West China. Integration of TB services in the hospitals needs to address the challenges of stakeholder motivations and resource allocation. Effective inter-organizational collaboration could help to improve the efficiency and quality of TB service. Key words: TB control, service delivery, integration, hospitals, China.


title: Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease

text: The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy” donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.