title: Enhanced nano-aerosol loading performance of multilayer PVDF nanofiber electret filters

text: Abstract Aerosol loading behavior of PVDF nanofiber electret filters using neutrally charged nano- and submicron aerosols was investigated experimentally for the first time. The loading behavior include variations of filtration efficiency and pressure drop and distribution of deposited aerosols in the filters all having the same fiber basis weight (3.060 gsm). Through the filtration efficiency variations of uncharged/charged, single-/multi-layer filters with aerosol loading, it was observed that mechanical PVDF filters had continuously increasing filtration efficiency, while PVDF electret filters had initially decreasing and subsequently increasing filtration efficiency until reaching 100% due to diminishing electrostatic effect and enhancing mechanical effect. By combining the pressure drop evolution of different filters during aerosol loading and detailed SEM images of the loaded filters, we have demonstrated that multilayer PVDF filters, especially the electret ones, could significantly slow down the pace of filter clogging (skin effect) and increase significantly the aerosol holding capacity during depth filtration. Generally, the multilayer nanofiber filters received the most aerosol deposit during depth filtration, whereas the single-layer nanofiber filters with the same basis weight of fibers received the most deposit during cake filtration. The multilayer nanofiber filters had approximately 70% aerosol deposit in the filter during depth filtration fully utilizing the full filter thickness, especially for the electret filters that had charged fibers, and only 30% deposit in the cake. On the contrary, the single-layer uncharged/charged nanofiber filters were exactly the reverse due to persistency of the skin effect with only 30% deposit in the filter mostly located in the upstream layer, yet 70% deposit in the cake. During depth filtration, the pressure drop per added mass deposit for the multilayer electret filter was very low at 11 Pa gsm−1, which was at least twice below any other nanofiber filters. This was all attributed to the uniform capture of aerosols by electrostatic effect across the entire filter depth from the upstream to downstream layers of the multilayer electret filter. The above conclusion was confirmed by the detailed SEM images taken across the different filter layers for the multilayer filter configuration. The 4-layer electret nanofiber filter with a 3.060-gsm basis weight has 4 times more aerosol holding capacity than the single uncharged/charged nanofiber filter with the same fiber basis weight in depth filtration. Based on the standpoint of highest efficiency and capacity with maximum pressure drop 800 Pa imposed on the filtration operation, the 4-layer nanofiber electret was the best among all 4 filters. It had 52% more aerosol holding capacity than the single layer uncharged nanofiber filter and 38% more capacity than the charged single-layer and the uncharged multilayer nanofiber filters. The multilayer PVDF electret filters have excellent filtration performance for long-term aerosol filtration and also great potential applications in the fields of personal health care and environmental protection.


COVID-19 and hydroxychloroquine: is the wonder drug failing?


title: Domestic Poultry and SARS Coronavirus, Southern China

text: SARS coronavirus injected intratracheally into chickens, turkeys, geese, ducks, and quail, or into the allantoic sac of their embryonating eggs, failed to cause disease or replicate. This finding suggests that domestic poultry were unlikely to have been the reservoir, or associated with dissemination, of SARS coronavirus in the animal markets of southern China.


title: Therapeutic Applications of Monoclonal Antibodies

text: ABSTRACT Researchers have sought therapeutic applications for monoclonal antibodies since their development in 1975. However, murine-derived monoclonal antibodies may cause an immunogenic response in human patients, reducing their therapeutic efficacy. Chimeric and humanized antibodies have been developed that are less likely to provoke an immune reaction in human patients than are murine-derived antibodies. Antibody fragments, bispecific antibodies, and antibodies produced through the use of phage display systems and genetically modified plants and animals may aid researchers in developing new uses for monoclonal antibodies in the treatment of disease. Monoclonal antibodies may have a number of promising potential therapeutic applications in the treatment of asthma, autoimmune diseases, cancer, poisoning, septicemia, substance abuse, viral infections, and other diseases.


title: The aqueous extract from Toona sinensis leaves inhibits microglia-mediated neuroinflammation

text: The leaves of Toona sinensis, a well-known traditional oriental medicine, have been prescribed for the treatment of enteritis and infection. Recently, aqueous extracts of Toona sinensis leaves (TSL-1) have demonstrated many biological effects both in vitro and in vivo. In the central nervous system, microglial activation and their proinflammatory responses are considered an important therapeutic strategy for neuroinflammatory disorders such as cerebral ischemia, Alzheimer's disease, and Parkinson's disease. The present study attempted to validate the effect of TSL-1 on microglia-mediated neuroinflammation stimulated by lipopolysaccharide (LPS). As inflammatory parameters, the production of nitric oxide (NO), inducible NO synthase, and tumor necrosis factor-α were evaluated. Our results demonstrate that TSL-1 suppresses LPS-induced NO production, tumor necrosis factor-α secretion, and inducible NO synthase protein expression in a concentration-dependent manner, without causing cytotoxicity. In addition, the inhibitory effects of TSL-1 in LPS-stimulated BV-2 microglia were extended to post-treatment suggesting the therapeutic potential of TSL-1. Therefore, this work provides the future evaluation of the role of TSL-1 in the treatment of neurodegenerative diseases by inhibition of inflammatory mediator production in activated microglia.


title: CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.


title: Lethal Outcome of Leptospirosis in Southern Russia: Characterization of Leptospira Interrogans Isolated from a Deсeased Teenager

text: This article describes a lethal case of leptospirosis that occurred in Southern Russia. The Leptospira strain was isolated and characterized using a microscopic agglutination test, MALDI-TOF mass spectrometry, targeted PCR, and high-throughput sequencing. We show that molecular and mass-spectrometry methods can be an alternative to conventional methods of leptospirosis diagnostics and Leptospira study, which require highly qualified staff and can be performed only at specialized laboratories. We also report the first whole genome of L. interrogans isolated in Russia.


title: Optimization of xanthatin extraction from Xanthium spinosum L. and its cytotoxic, anti-angiogenesis and antiviral properties

text: The aqueous extraction of the sesquiterpene lactone xanthatin from Xanthium spinosum L. favours the conversion of xanthinin (1) to xanthatin (2) via the loss of acetic acid. The cytotoxic (Hep-G2 and L1210 human cell lines) and antiviral activities of isolated xanthatin are established. This natural compound shows significant cytotoxicity against the Hep-G2 cell line and our experimental results reveal its strong anti-angiogenesis capacity in vitro. The structure of xanthatin is determined by spectroscopic methods and for the first time confirmed by X-ray diffraction.


title: Synthesis and affinity to DNA of phenylbenzoimidazoles and benzoimidazo[1,2-c]quinazolines

text: Novel N-(benzoimidazophenyl)dialkylaminoalkylamides and 6-dialkylaminoalkylbenzoimidazo[1,2-c]quinazolines were prepared as potential interferon inducers and antiviral agents. They were screened for the DNA affinity by the ethidium bromide displacement assay. It was shown that the lg K(a) values of the compounds containing tetracyclic benzoimidazo[1,2-c]quinazoline fragment are approximately one order magnitude greater than those of the corresponding acyclic phenylbenzoimidazole derivatives.


title: Current Progress of Virus-mimicking Nanocarriers for Drug Delivery

text: Nanomedicines often involve the use of nanocarriers as a delivery system for drugs or genes for maximizing the therapeutic effect and/or minimizing the adverse effect. From drug administration to therapeutic activity, nanocarriers must evade the host's immune system, specifically and efficiently target and enter the cell, and release their payload into the cell cytoplasm by endosomal escape. These processes constitute the early infection stage of viruses. Viruses are a powerful natural nanomaterial for the efficient delivery of genetic information by sophisticated mechanisms. Over the past two decades, many virus-inspired nanocarriers have been generated to permit successful drug and gene delivery. In this review, we summarize the early infection machineries of viruses, of which the part has so far been utilized for delivery systems. Furthermore, we describe basics and applications of the bio-nanocapsule, which is a hepatitis B virus-mimicking nanoparticle harboring nearly all activities involved in the early infection machineries (i.e., stealth activity, targeting activity, cell entry activity, endosomal escaping activity).


Population-based hospitalization incidence of respiratory viruses in community-acquired pneumonia in children younger than 5 years of age


docid: bxucakch

title: COVID‐19: Desolation and catharsis from Old Europe


title: Limited shedding of an S-InDel strain of porcine epidemic diarrhea virus (PEDV) in semen and questions regarding the infectivity of the detected virus

text: Abstract PEDV is mainly transmitted by the oro-fecal route although PEDV shedding in semen has already been shown for an S-non-InDel PEDV strain infection. The aim of this study was to determine if PEDV can be shed in semen from SPF (specific pathogens free) boars infected by a French S-InDel PEDV strain (PEDV/FR/001/2014) and in case of positive semen to determine the infectivity of that semen. Both infected boars had diarrhea after inoculation and shed virus in feces. PEDV genome was also detected by RT-qPCR in the sperm-rich fraction of semen (6.94 × 103 and 4.73 × 103 genomic copies/mL) from the two boars infected with the S-InDel PEDV strain but only once at 7DPI. In addition, PEDV RNA in Peyer’s patches and in mesenteric lymph nodes was also present for the two inoculated boars. The PEDV positive semen (S-non-InDel and S-InDel) sampled during a previous trial and in this boar trial were inoculated to six SPF weaned pigs. The inoculated piglets did not seroconvert and did not shed virus throughout the duration of the study except for one pig at 18 DPI. But, PEDV could be detected in intestinal tissues such as duodenum, jejunum and jejunum Peyer’s patches by RT-qPCR except for one pig. Even if PEDV genome has been detected in semen, experimental infection of piglets with positive semen failed to conclude to the infectivity of the detected PEDV.


docid: xftxcgeu

title: Adding the spatial dimension to the social network analysis of an epidemic: Investigation of the 2007 outbreak of equine influenza in Australia

text: Abstract Equine influenza is a highly contagious and widespread viral respiratory disease of horses and other equid species, characterised by fever and a harsh dry cough. In 2007, in the first reported outbreak in Australia, the virus spread through the horse populations of two states within 4 months. Most of the geographic spread occurred within the first 10 days and was associated with the movement of infected horses prior to the implementation of movement controls. This study applies social network analysis to describe spread of equine influenza between horse premises infected in the early outbreak period, identifying spread occurring through a contact network and secondary local spatial spread. Social networks were constructed by combining contact-tracing data on horse movements with a distance matrix between all premises holding horses infected within the first 10 days of the outbreak. These networks were analysed to provide a description of the epidemic, identify premises that were central to disease spread and to estimate the relative proportion of premises infected through infected horse movements and through local spatial spread. We then explored the effect of distance on disease spread by estimating the range of local spread (through direct contact, transmission on fomites and windborne transmission) based on the level of fragmentation in the network and also by directly estimating the shape of the outbreak's spatial transmission kernel. During the first 10 days of this epidemic, 197 horse premises were infected; 70 of these were included in the contact-traced network. Most local spread occurred within 5km. Local spread was estimated to have occurred up to a distance of 15.3km – based on the contact-and-proximity network – and at a very low incidence beyond this distance based on the transmission kernel estimate. Of the 70 premises in the contact network, spread to 14 premises (95% CI: 9, 20 premises) was likely to have occurred through local spatial spread from nearby infected premises, suggesting that 28.3% of spread in the early epidemic period was ‘network-associated’ (95% CI: 25.6, 31.0%). By constructing a ‘maximal network’ of contact and proximity (based on a distance cut-off of 15.3km), 44 spatial clusters were described, and the horse movements that initiated infection in these locations were identified. Characteristics of the combined network, incorporating both spatial and underlying contact relationships between infected premises, explained the high rate of spread, the sequence of cluster formation and the widespread dispersal experienced in the early phase of this epidemic. These results can inform outbreak control planning by guiding the imposition of appropriate control zone diameters around infected premises and the targeting of surveillance and interventions.


title: Catalysis-in-a-Box: Robotic Screening of Catalytic Materials in the Time of COVID-19 and Beyond

text: This work describes the design and implementation of an automated device for catalytic materials testing by direct modifications to a gas chromatograph (GC). The setup can be operated as a plug-flow isothermal reactor and enables the control of relevant parameters such as reaction temperature and reactant partial pressures directly from the GC. High-quality kinetic data (including reaction rates, product distributions, and activation barriers) can be obtained at almost one-tenth of the fabrication cost of analogous commercial setups. With these key benefits including automation, low cost, and limited experimental equipment instrumentation, this implementation is intended as a high-throughput catalyst screening reactor that can be readily utilized by materials synthesis researchers to assess the catalytic properties of their synthesized structures in vapor-phase chemistries.


docid: muztaqox

title: Gastrointestinal and liver manifestations in patients with COVID-19

text: As the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread over the world, the World Health Organization has declared the outbreak of COVID-19 an international public health emergency. Besides typical respiratory symptoms and signs of COVID-19, digestive symptoms and liver injury have been frequently reported during the course of the disease. In this review, we summarized the recent studies reporting of gastrointestinal and liver manifestations during the course of COVID-19. Digestive symptoms, including anorexia, nausea, vomiting, and diarrhea, are not uncommon in patients with COVID-19, and in some cases digestive symptoms may occur in the absence of any respiratory symptoms. Furthermore, SARS-CoV-2 could be detected in the stool of infected patients, implicating the possibility of fecal–oral transmission. Attention should also be paid to monitor liver function during the course of COVID-19, especially in patients with higher disease severity.


title: Rescue of chimeric adenoviral vectors to expand the serotype repertoire

text: The successful use of any adenoviral vectors is predicated upon the use of a serotype that is not neutralized by circulating antibodies. However, efforts to develop a diverse repertoire of serologically distinct adenovirus vectors may be hindered by the necessity to generate cell lines to allow for the successful propagation of vectors deleted of essential genes. A strategy to construct chimeric adenoviruses whereby the rescue and propagation of an E1 deleted HAdV-B – derived adenoviral vector can be achieved using existing cell lines such as HEK 293 is reported. It is further shown that this strategy may be more widely applicable.


title: Human rhinoviruses and enteroviruses in influenza-like illness in Latin America

text: BACKGROUND: Human rhinoviruses (HRVs) belong to the Picornaviridae family with high similarity to human enteroviruses (HEVs). Limited data is available from Latin America regarding the clinical presentation and strains of these viruses in respiratory disease. METHODS: We collected nasopharyngeal swabs at clinics located in eight Latin American countries from 3,375 subjects aged 25 years or younger who presented with influenza-like illness. RESULTS: Our subjects had a median age of 3 years and a 1.2:1.0 male:female ratio. HRV was identified in 16% and HEV was identified in 3%. HRVs accounted for a higher frequency of isolates in those of younger age, in particular children < 1 years old. HRV-C accounted for 38% of all HRVs detected. Phylogenetic analysis revealed a high proportion of recombinant strains between HRV-A/HRV-C and between HEV-A/HEV-B. In addition, both EV-D68 and EV-A71 were identified. CONCLUSIONS: In Latin America as in other regions, HRVs and HEVs account for a substantial proportion of respiratory viruses identified in young people with ILI, a finding that provides additional support for the development of pharmaceuticals and vaccines targeting these pathogens.


title: Bradford Hill’s criteria, emerging zoonoses, and One Health

text: Abstract Zoonoses constitute more than 60% of infectious diseases and 75% of emerging infectious diseases. Inappropriate overemphasis of specialization of disciplines has ignored public health. Identifying the causes of disease and determining how exposures are related to outcomes in “emerging zoonoses” affecting multiple species are considered to be the hallmarks of public health research and practice that compels the adoption of “One Health”. The interactions within and among populations of vertebrates in the causation and transmissions of emerging zoonotic diseases are inherently dynamic, interdependent, and systems based. Disease causality theories have moved from one or several agents causing disease in a single species, to one infectious agent causing disease in multiple species-emerging zoonoses. Identification of the causative pathogen components or structures, elucidating the mechanisms of species specificity, and understanding the natural conditions of emergence would facilitate better derivation of the causal mechanism. Good quality evidence on causation in emerging zoonoses affecting multiple species makes a strong recommendation under the One Health approach for disease prevention and control from diagnostic tests, treatment, antimicrobial resistance, preventive vaccines, and evidence informed health policies. In the tenets of One Health, alliances work best when the legitimate interests of the different partners combine to prevent and control emerging zoonoses.


COVID-19: an occupational health view from South Africa


title: Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis.

text: Summary The coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented threat to global public health. Herein, we utilized a combination of targeted and untargeted tandem mass spectrometry to analyse the plasma lipidome and metabolome in mild, moderate and severe COVID-19 patients and healthy controls. A panel of 10 plasma metabolites effectively distinguished COVID-19 patients from healthy controls (AUC = 0.975). Plasma lipidome of COVID-19 resembled that of monosialodihexosyl gangliosides (GM3)-enriched exosomes, with enhanced levels of sphingomyelins (SMs) and GM3s, and reduced diacylglycerols (DAGs). Systems evaluation of metabolic dysregulation in COVID-19 was performed using multiscale embedded differential correlation network analyses. Using exosomes isolated from the same cohort, we demonstrated that exosomes of COVID-19 patients with elevating disease severity were increasingly enriched in GM3s. Our work suggests that GM3-enriched exosomes may partake in pathological processes related to COVID-19 pathogenesis, and presents the largest repository on the plasma lipidome and metabolome distinct to COVID-19.


title: Merkel Cell Polyomavirus DNA in Respiratory Specimens from Children and Adults

text: Merkel cell polyomavirus (MCPyV) DNA was detected in 7 (1.3%) of 526 respiratory tract samples from patients in Australia with upper or lower respiratory tract symptoms. Partial T antigen and major capsid protein sequences of MCPyV identified in respiratory secretions showed high homology (99%–100%) to those found in Merkel cell carcinoma.


title: The Diagnosis of Pneumonia in a Pregnant Woman with COVID-19 Using Maternal Lung Ultrasound

text: Abstract Lung ultrasound examination has been demonstrated to be an accurate imaging method to detect pulmonary and pleural conditions. During pregnancy, there is a need for a rapid assessment of the maternal lung in patients suspected to have COVID-19. We report our experience on lung ultrasound examination in the diagnosis of Sars-Cov-2 pneumonia in a pregnant woman. Typical ultrasound features of this pulmonary pathology, including diffuse hyperechoic vertical artifacts with thickened pleural line and “white lung” with patchy distribution, were observed. We suggest point of care lung ultrasound examination as a diagnostic imaging tool in pregnant women with suspected COVID-19.


title: Aerosols and splatter in dentistry A brief review of the literature and infection control implications

text: ABSTRACT Background Aerosols and droplets are produced during many dental procedures. With the advent of the droplet-spread disease severe acute respiratory syndrome, or SARS, a review of the infection control procedures for aerosols is warranted. Types of Studies Reviewed The authors reviewed representative medical and dental literature for studies and reports that documented the spread of disease through an airborne route. They also reviewed the dental literature for representative studies of contamination from various dental procedures and methods of reducing airborne contamination from those procedures. Results The airborne spread of measles, tuberculosis and SARS is well-documented in the medical literature. The dental literature shows that many dental procedures produce aerosols and droplets that are contaminated with bacteria and blood. These aerosols represent a potential route for disease transmission. The literature also documents that airborne contamination can be minimized easily and inexpensively by layering several infection control steps into the routine precautions used during all dental procedures. Clinical Implications In addition to the routine use of standard barriers such as masks and gloves, the universal use of pre-procedural rinses and high-volume evacuation is recommended.


title: Antiviral activity of cationic amphiphilic drugs

text: Introduction: Emerging and reemerging viral infections represent a major concern for human and veterinary public health and there is an urgent need for the development of broad-spectrum antivirals. Areas covered: A recent strategy in antiviral research is based on the identification of molecules targeting host functions required for infection of multiple viruses. A number of FDA-approved drugs used to treat several human diseases are cationic amphiphilic drugs (CADs) that have the ability to accumulate inside cells affecting several structures/functions hijacked by viruses during infection. In this review we summarized the CADs’ chemical properties and effects on the cells and reported the main FDA-approved CADs that have been identified so far as potential antivirals in drug repurposing studies. Expert commentary: Although there have been concerns regarding the efficacy and the possible side effects of the off-label use of CADs as antivirals, they seem to represent a promising starting point for the development of broad-spectrum antiviral strategies. Further knowledge about their mechanism of action is required to improve their antiviral activity and to reduce the risk of side effects.


title: Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey

text: BACKGROUND: The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area. METHODS: We conducted an online, cross-sectional social media survey from March 14 – April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S. RESULTS: The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement. CONCLUSION: These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed.


title: The impact of multiple infections on wild animal hosts: a review

text: Field parasitological studies consistently demonstrate the reality of polyparasitism in natural systems. However, only recently, studies from ecological and evolutionary fields have emphasised a broad spectrum of potential multiple infections-related impacts. The main goal of our review is to reunify the different approaches on the impacts of polyparasitism, not only from laboratory or human medical studies but also from field or theoretical studies. We put forward that ecological and epidemiological determinants to explain the level of polyparasitism, which regularly affects not only host body condition, survival or reproduction but also host metabolism, genetics or immune investment. Despite inherent limitations of all these studies, multiple infections should be considered more systematically in wildlife to better appreciate the importance of parasite diversity in wildlife, cumulative effects of parasitism on the ecology and evolution of their hosts.


title: Bradycardia in Patients With COVID-19: A Calm Before the Storm?

text: Cardiac manifestations of coronavirus disease 19 (COVID-19), including arrhythmia, have been described in the literature. However, to our knowledge, association of COVID-19 with bradycardia has not been reported. This case study describes sinus bradycardia as a potential manifestation of COVID-19. This is a retrospective case series of four patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, admitted to St. Luke’s University Health Network ICU between 24 March 2020 and 5 April 2020. Medical records of these patients were reviewed using the EPIC electronic health record system. Demographic, clinical, laboratory, and treatment data were reviewed against periods of bradycardia in each patient. The patient group comprised two males and two females. Two patients had pre-existing cardiovascular (CV) comorbidities but no history of arrythmias. Heart rates ranged between 66 and 88 beats/min on admission. The lowest rates during bradycardia were between 42 and 49 beats/min. The onset of sinus bradycardia in patients 1, 2, and 3 were day nine, 15, and five of illness, respectively. Patient 4 had three episodes of bradycardia, starting on day 10 of illness. Patients’ bradycardia episodes lasted one to 14 days. During bradycardia, maximum body temperatures ranged between 99.9 and 100.2 degree Fahrenheit. Patients 2, 3, and 4 required vasopressors to maintain mean arterial pressure > 65 mmHg during episodes. All four patients were on propofol at some point during bradycardia with patients 1, 2, and 3 also receiving dexmedetomidine. There was no consistent correlation of these medications with bradycardia. Electrocardiogram (ECG) findings included sinus bradycardia. Prolonged QTc interval observed in patient 2 on admission improved during bradycardia. Transient sinus bradycardia is a possible manifestation of COVID-19 and is important for close CV surveillance. Etiology can be multifactorial, but severe hypoxia, inflammatory damage of cardiac pacemaker cells, and exaggerated response to medications are possible triggers. High levels of pro-inflammatory cytokines may act directly on the sinoatrial (SA) node contributing to the development of bradycardia. This may be a warning sign of the onset of a serious cytokine storm. An increased awareness of possible exaggerated bradycardia response is important to consider with the use of empiric medications which have arrhythmogenic effects.


title: Integrating Disaster Preparedness Into a Community Health Nursing Course: One School's Experience

text: It is not practical to wait for a disaster, whether natural or human-made, to learn how to respond and provide specialized care. The Long Island University School of Nursing in Brooklyn, New York, has developed a specific educational experience for undergraduate nursing students enrolled in community health. The course is offered in the senior semester and includes didactic material based on the International Nursing Coalition for Mass Casualty Education–recommended competencies. Students are given the opportunity to apply the learning and develop additional skills by participating in a mock drill. Although anecdotal comments from the students indicate that the coursework has been helpful, additional research is planned to evaluate the program.


title: Executive summary of imported infectious diseases after returning from foreign travel: Consensus document of the Spanish Society for Infectious Diseases and Clinical Microbiology (SEIMC)

text: In a global world, knowledge of imported infectious diseases is essential in daily practice, both for the microbiologist–parasitologist and the clinician who diagnoses and treats infectious diseases in returned travelers. Tropical and subtropical countries where there is a greater risk of contracting an infectious disease are among the most frequently visited tourist destinations. The SEIMC considers it appropriate to produce a consensus document that will be useful to primary care physicians as well as specialists in internal medicine, infectious diseases and tropical medicine who help treat travelers returning from tropical and sub-tropical areas with infections. Preventive aspects of infectious diseases and infections imported by immigrants are explicitly excluded here, since they have been dealt with in other SEIMC documents. Various types of professionals (clinicians, microbiologists, and parasitologists) have helped produce this consensus document by evaluating the available evidence-based data in order to propose a series of key facts about individual aspects of the topic. The first section of the document is a summary of some of the general aspects concerning the general assessment of travelers who return home with potential infections. The main second section contains the key facts (causative agents, diagnostic procedures and therapeutic measures) associated with the major infectious syndromes affecting returned travelers [gastrointestinal syndrome (acute or persistent diarrhea); febrile syndrome with no obvious source of infection; localized cutaneous lesions; and respiratory infections]. Finally, the characteristics of special traveler subtypes, such as pregnant women and immunocompromised travelers, are described.


title: Epidemiology of Severe Acute Respiratory Infection (SARI) Cases at a sentinel site in Egypt, 2013–15

text: BACKGROUND: Sentinel surveillance for severe acute respiratory infection (SARI) in Egypt began in 2006 and occurs at eight sites. Avian influenza is endemic, and human cases of influenza A (H5N1) have been reported annually since 2006. This study aimed to describe the epidemiology of SARI at a major sentinel site in the country. METHODS: Data included in the study were collected from a major SARI sentinel site in Egypt during three consecutive years (2013–15). RESULTS: A total of 1254 SARI patients conforming to the WHO case definition were admitted to the sentinel site, representing 5.6% of admitted patients for all causes and 36.6% of acute respiratory infection patients. A total of 99.7% of the patients were tested, and 21.04% tested positive; 48.7% of cases involved influenza A viruses, while 25% involved influenza B. The predominant age group was under 5 years of age, accounting for 443 cases. The seasonality of the influenza data conformed to the Northern Hemisphere pattern. CONCLUSIONS: The present study’s results show that SARI leads to substantial morbidity in Egypt. There is a great need for high-quality data from the SARI surveillance system in Egypt, especially with endemic respiratory threats such as influenza A (H5N1) in Egypt.


title: Blood Component Use in Critical Care in Patients with COVID‐19 Infection: A Single Centre Experience

text: There has been a significant surge in admissions to critical care during the COVID‐19 pandemic. At present, the demands on blood components have not been described. We reviewed their use during the first 6 weeks of the outbreak from 3(rd) March 2020 in a tertiary‐level critical care department providing veno‐venous extracorporeal membrane oxygenation (vv‐ECMO). 265 patients were reviewed ‐ 235 not requiring ECMO and 30 requiring vv‐ECMO. In total, 50 patients required blood components during their critical care admission. Red cell concentrates were the most frequently transfused component in COVID‐19 infected patients with higher rates of use during vv‐ECMO. The use of fresh frozen plasma, cryoprecipitate and platelet transfusions was low in a period prior to the use of convalescent plasma.


title: Viral Exanthem with “Pin and Needles Sensation” on Extremities of COVID-19 Patient

text: Abstract Cutaneous manifestation is a newly reported clinical manifestation of COVID-19 infection. The clinical description of cutaneous manifestation is still not fully described. Our patient, a medical personnel, had viral exanthem distributed in the extremities along with “pin and needles sensation” which differ from the previously published paper on cutaneous manifestation. The differential diagnosis of drug-induced skin rash and hand-foot-mouth disease have already been ruled out based on the patient's previous history and course of disease.


title: Porcine epidemic diarrhea virus N protein prolongs S-phase cell cycle, induces endoplasmic reticulum stress, and up-regulates interleukin-8 expression

text: Abstract Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease of swine caused by porcine epidemic diarrhea virus (PEDV). The porcine intestinal epithelial cell is the PEDV target cell. In this study, we established a porcine intestinal epithelial cell (IEC) line which can stably express PEDV N protein. We also investigate the subcellular localization and function of PEDV N protein by examining its effects on cell growth, cycle progression, interleukin-8 (IL-8) expression, and survival. The results show that the PEDV N protein localizes in the endoplasmic reticulum (ER), inhibits the IEC growth and prolongs S-phase cell cycle. The S-phase is prolonged which is associated with a decrease of cyclin A transcription level and an increase of cyclin A degradation. The IEC expressing PEDV N protein can express higher levels of IL-8 than control cells. Further studies show that PEDV N protein induces ER stress and activates NF-κB, which is responsible for the up-regulation of IL-8 and Bcl-2 expression. This is the first report to demonstrate that PEDV N protein can induce cell cycle prolongation at the S-phase, ER stress and up-regulation interleukin-8 expression. These findings provide novel information on the function of the PEDV N protein and are likely to be very useful in understanding the molecular mechanisms responsible for PEDV pathogenesis.


title: Tumor necrosis factor α (TNF-α) receptor-I is required for TNF-α-mediated fulminant virus hepatitis caused by murine hepatitis virus strain-3 infection

text: Abstract TNF-α plays an essential role in the pathogenesis of fulminant virus hepatitis (FH) caused by infection with murine hepatitis virus strain-3 (MHV-3). However, the specific TNF-α receptors (TNFR) involved in this disease and how they mediate this effect are uncertain. Here, we showed that the expression of TNFR1 and TNFR2 in the liver and spleen was triggered by MHV-3. However, only TNFR1−/− mice were resistant to MHV-3 mediated FH, as displayed by a dramatic decrease in tissue necrosis and cell apoptosis in the infected spleens and livers from TNFR1−/− mice, as well as prolonged survival in these mice compared to wild type littermate controls. Mechanistically, TNFR1 deficiency directly impeded the serum and tissue levels of fibrinogen-like protein 2 (FGL2), a virus-induced procoagulant molecule that promotes cell apoptosis. Additionally, the expression of apoptosis-associated molecules, Fas and Fas ligand (FasL) in the infected organs from TNFR1−/− mice were also decreased. Moreover, the infiltration of neutrophils rather than Foxp3+ regulatory T cells, which produce proinflammatory factors and FGL2 directly, into the infected liver and spleen tissues was also decreased in TNFR1−/− mice. These combined results indicate that signaling through TNFR1 plays an essential role in the pathogenesis of FH caused by MHV-3 infection, and interruption of this signaling pathway could be useful for clinical therapy.


title: Discrimination of Kawasaki disease with concomitant adenoviral detection differentiating from isolated adenoviral infection

text: PURPOSE: Human adenovirus infection mimics Kawasaki disease (KD) but can be detected in KD patients. The aim of this study was to determine the clinical differences between KD with adenovirus infection and only adenoviral infection and to identify biomarkers for prediction of adenovirus-positive KD from isolated adenoviral infection. METHODS: A total of 147 patients with isolated adenovirus were identified by quantitative polymerase chain reaction. In addition, 11 patients having KD with adenovirus, who were treated with intravenous immunoglobulin therapy during the acute phase of KD were also evaluated. RESULTS: Compared with the adenoviral infection group, the KD with adenovirus group was significantly associated with frequent lip and tongue changes, skin rash and changes in the extremities. In the laboratory parameters, higher C-reactive protein (CRP) level and presence of hypoalbuminemia and sterile pyuria were significantly associated with the KD group. In the multivariate analysis, lip and tongue changes (odds ratio [OR], 1.416; 95% confidence interval [CI], 1.151–1.741; P=0.001), high CRP level (OR, 1.039; 95% CI 1.743–1.454; P= 0.021) and sterile pyuria (OR 1.052; 95% CI 0.861–1.286; P=0.041) were the significant predictive factors of KD. In addition, the cutoff CRP level related to KD with adenoviral detection was 56 mg/L, with a sensitivity of 81.8% and a specificity of 75.9%. CONCLUSION: Lip and tongue changes, higher serum CRP level and sterile pyuria were significantly correlated with adenovirus-positive KD.


The impact of the COVID‐19 pandemic on gastroenterology trainees in Australia


title: Neurological manifestations of COVID-19: a systematic review

text: INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global spread of coronavirus disease (COVID-19). Our understanding of the impact this virus has on the nervous system is limited. Our review aims to inform and improve decision-making among the physicians treating COVID-19 by presenting a systematic analysis of the neurological manifestations experienced within these patients. METHODS: Any study, released prior to May 20, 2020, that reported neurological manifestations in patients infected by SARS-CoV-2 was systematically reviewed using the PRISMA (Preferred Reporting Items for Systemic review and Meta-Analysis) statement. RESULTS: Our systematic review included data from 37 articles: twelve retrospective studies, two prospective studies, and the rest case reports/series. The most commonly reported neurological manifestations of COVID-19 were myalgia, headache, altered sensorium, hyposmia, and hypogeusia. Uncommonly, COVID-19 can also present with central nervous system manifestations such as ischemic stroke, intracerebral hemorrhage, encephalo-myelitis, and acute myelitis, peripheral nervous manifestations such as Guillain-Barré syndrome and Bell’s palsy, and skeletal muscle manifestations such as rhabdomyolysis. CONCLUSION: While COVID-19 typically presents as a self-limiting respiratory disease, it has been reported in up to 20% of patients to progress to severe illness with multi-organ involvement. The neurological manifestations of COVID-19 are not uncommon, but our study found most resolve with treatment of the underlying infection. Although the timeliness of this review engages current challenges posed by the COVID-19 pandemic, readers must not ignore the limitations and biases intrinsic to an early investigation.


title: Analysis of seasonal tendencies in pediatric Henoch–Schönlein purpura and comparison with outbreak of infectious diseases

text: Henoch–Schönlein purpura (HSP) is one of the most common vasculitis in children. This study was aimed at identifying seasonal trends and epidemiologic features of pediatric HSP patients through public data to analyze the correlation of HSP and prevalence of a specific respiratory or enteric virus. We extracted information on pediatric HSP patients categorized into 4 age groups and data on 8 respiratory and 4 enteric viruses were extracted from national data. We used the decomposition of time series analysis and correlation analysis to identify the incidence of HSP and the prevalence of each virus. From 2013 to 2016, 16,940 patients under the age of 18 were diagnosed with HSP in Korea, 6203 (36.6%) were diagnosed with HSP in middle childhood. Spring had the largest number of patients (5252, 31.0%), and summer had the smallest number of patients (3224, 19.0%). The largest and smallest number of cases occurred in March (1949, 11.5%) and August (959, 5.7%), respectively. However, among the adolescents, more patients were diagnosed in the summer (985, 24.8%) than in the fall (760, 19.1%). The positive detection counts of most viruses showed apparent seasonal variations. Depending on the age group, the epidemic patterns of influenza and rotaviruses were temporally and statistically similar to that of HSP. We have confirmed that the occurrence of pediatric HSP in Korea shows a seasonal tendency, which is age-dependent and related to exposure to infectious agents and suggest some respiratory or enteric viruses may play an important role in pathophysiology.


Ancillary considerations for endodontic emergency treatment of Covid‐19 positive patients


title: Plasma membrane cholesterol is required for efficient pseudorabies virus entry

text: Abstract Alphaherpesviruses comprise closely related viruses of man and animal, including herpes simplex virus, varicella-zoster virus and pseudorabies virus (PRV). Here, using methyl-beta-cyclodextrin and fluorescently tagged PRV, we directly show that depletion of cholesterol from the plasma membrane of host cells significantly reduces PRV entry. Cholesterol depletion did not reduce PRV attachment, but stalled virus particles at the plasma membrane before penetration of the cell. Cholesterol depletion results in destabilization of lipid raft microdomains in the plasma membrane, which have been shown before to be involved in efficient entry of different viruses. A significant fraction of PRV virions appears to localize juxtaposed to GM1, a lipid raft marker, during entry. Together, these data indicate that cholesterol and possibly cholesterol-rich lipid rafts may be important during PRV entry.


title: Emerging drug development technologies targeting ubiquitination for cancer therapeutics

text: Abstract Development of effective cancer therapeutic strategies relies on our ability to interfere with cellular processes that are dysregulated in tumors. Given the essential role of the ubiquitin proteasome system (UPS) in regulating a myriad of cellular processes, it is not surprising that malfunction of UPS components is implicated in numerous human diseases, including many types of cancer. The clinical success of proteasome inhibitors in treating multiple myeloma has further stimulated enthusiasm for targeting UPS proteins for pharmacological intervention in cancer treatment, particularly in the precision medicine era. Unfortunately, despite tremendous efforts, the paucity of potent and selective UPS inhibitors has severely hampered attempts to exploit the UPS for therapeutic benefits. To tackle this problem, many groups have been working on technology advancement to rapidly and effectively screen for potent and specific UPS modulators as intracellular probes or early-phase therapeutic agents. Here, we review several emerging technologies for developing chemical- and protein-based molecules to manipulate UPS enzymatic activity, with the aim of providing an overview of strategies available to target ubiquitination for cancer therapy.


title: Preliminary support for a “dry swab, extraction free” protocol for SARS-CoV-2 testing via RT-qPCR

text: The urgent need for massively scaled clinical or surveillance testing for SARS-CoV-2 has necessitated a reconsideration of the methods by which respiratory samples are collected, transported, processed and tested. Conventional testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab, storage of the swab during transport in universal transport medium (UTM), extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). As testing has scaled across the world, supply chain challenges have emerged across this entire workflow. Here we sought to evaluate how eliminating the UTM storage and RNA extraction steps would impact the results of molecular testing. Using paired mid-turbinate swabs self-collected by 11 individuals with previously established SARS-CoV-2 positivity, we performed a comparison of conventional (swab → UTM → RNA extraction → RT-qPCR) vs. simplified (direct elution from dry swab → RT-qPCR) protocols. Our results suggest that dry swabs eluted directly into a simple buffered solution (TE) can support molecular detection of SARS-CoV-2 via endpoint RT-qPCR without substantially compromising sensitivity. Although further confirmation with a larger sample size and variation of other parameters is necessary, these results are encouraging for the possibility of a simplified workflow that could support massively scaled testing for COVID-19 control.


title: COVID-19 AND THE GLOBAL IMPACT ON COLORECTAL PRACTICE AND SURGERY

text: BACKGROUND: The novel SARS-Cov-2 virus that emerged in December 2019 causing the COVID-19 disease has led to sudden national reorganization and delivery of health care systems globally. The purpose of this survey was to assess the global impact of the coronavirus on the delivery of colorectal practice and surgery. Materials & Method: A panel of International Society of University Colon & Rectal Surgeons selected 22 questions that were included into a questionnaire. The questionnaire was distributed electronically to ISUCRS fellows, other surgeons on our database and on social media. The questionnaire remained open from April 16-28, 2020. RESULTS: 287 surgeons completed the survey. 90% were colorectal specialists or general surgeons with an interest in colorectal diseases. COVID-19 had impacted the practice of 96% surgeons and 52% were now using telemedicine. 66% stated that elective colorectal cancer surgery (ECCS) could proceed but with perioperative precautions. 19.5% of respondents stated that provision of personal protection equipment was the most important perioperative precaution, however, this was only being provided in 9.1% of hospitals. 64% of surgeons were offering minimally invasive surgery, however, 44% stated that there was not enough information about the safety of loss of intrabdominal CO2 gas during the COVID-19 pandemic. 61% of surgeons were prepared to defer ECCS, with 29% willing to defer for up to 8 weeks. CONCLUSIONS: Our survey has demonstrated that globally COVID-19 has affected the ability of colorectal surgeons to offer care to practice. Various practical adaptation strategies have been discussed in this manuscript.


title: Investigation on the contaminant distribution with improved ventilation system in hospital isolation rooms: Effect of supply and exhaust air diffuser configurations

text: Abstract This study, that is practice-based learning in a real hospital construction project, has evaluated the ventilation performance of three strategies in the protection of health care workers and HVAC control for airborne infectious diseases induced by contaminated exhaled air from patients in a negative pressure isolation room. This paper examines air flow path and airborne pollutant distribution by computational fluid dynamics modeling and field measurement. In hospitals, the risk of virus diffusion mainly depends on air flow behavior and changes in direction caused by supply air and exhaust air locations. An improved isolation room ventilation strategy has been suggested, and is found to be the most efficient in removing contaminants based on the observations and simulation results from three ventilation systems. The results show that ventilation systems utilizing the “low-level extraction” technique are very effective at removing pollutants in the human breathing zone. A new clean isolation room ventilation strategy has been developed that employs two exhaust air grilles on the wall behind the bed at low floor level, coupled with a fan filter unit, and is found to have the highest pollutant removal efficiency.


title: Exposure to multiple air pollutants and the incidence of coronary heart disease: A fine-scale geographic analysis

text: Abstract Geographical variations in cardiovascular disease rates have been linked to individual air pollutants. Investigating the relation between cardiovascular disease and exposure to a complex mixture of air pollutants requires holistic approaches. We assessed the relationship between exposure to multiple air pollutants and the incidence of coronary heart disease (CHD) in a general population sample. We collected data in the Lille MONICA registry (2008–2011) on 3268 incident cases (age range: 35–74). Based on 20 indicators, we derived a composite environmental score (SEnv) for cumulative exposure to air pollution. Poisson regression models were used to analyse associations between CHD rates on one hand and SEnv and each single indicator on the other (considered in tertiles, where T3 is the most contaminated). We adjusted models for age, sex, area-level social deprivation, and neighbourhood spatial structure. The incidence of CHD was a spatially heterogeneous (p=0.006). There was a significant positive association between SEnv and CHD incidence (trend p=0.0151). The relative risks [95%CI] of CHD were 1.08 [0.98–1.18] and 1.16 [1.04–1.29] for the 2nd and 3rd tertile of SEnv exposure. In the single pollutant analysis, PM10, NO2, cadmium, copper, nickel, and palladium were significantly associated with CHD rates. Multiple air pollution was associated with an increased risk of CHD. Single pollutants reflecting road traffic pollution were the most strongly associated with CHD. Our present results are consistent with the literature data on the impact of road traffic on the CHD risk in urban areas.


title: In vitro effects of lipopolysaccharides and mycobacterial cell wall components on swine alveolar macrophages

text: The possible activation of swine alveolar macrophages (AM) by lipopolysaccharides (LPS) and mycobacterial cell wall components such as muramyl dipeptide (MDP) and interphase material (IPM) was investigated. Swine AM were harvested by post mortem lung washings and the following functions were assayed: adherence and spreading in cultures; phagocytosis of 51Cr-labelled chicken red cells; cytostatic activity against xenogeneic tumour cells (P815 mastocytoma cells); monokine synthesis; interferon and LAF (lymphocyte activating factor or inter-Ieukin-1). Incubation of swine AM with either MDP, LPS or IPM (0·1 μg to 100 μg/ml) for 24 hours did not affect the cell viability but increased their adherence and spreading slightly. Phagocytosis was not markedly modified. Under the same experimental conditions, the unstimulated AM cultures exhibited a strong cytostatic activity which was not modified by these components. No interferon synthesis could be observed in the normal or stimulated AM cultures. In contrast, LAF activity was consistently increased after 48 hours of incubation with LPS, whereas MDP produced this effect only in some experiments.


title: MERS-CoV infection is associated with downregulation of genes encoding Th1 and Th2 cytokines/chemokines and elevated inflammatory innate immune response in the lower respiratory tract

text: Abstract MERS-CoV, a highly pathogenic virus in humans, is associated with high morbidity and case fatality. Inflammatory responses have a significant impact on MERS-CoV pathogenesis and disease outcome. However, CD4+ T-cell induced immune responses during acute MERS-CoV infection are barely detectable, with potent inhibition of effector T cells and downregulation of antigen presentation. The local pulmonary immune response, particularly the Th1 and Th2-related immune response during acute severe MERS-CoV infection is not fully understood. In this study, we offer the first insights into the pulmonary gene expression profile of Th1 and Th2-related cytokines/chemokines (Th1 & Th2 responses) during acute MERS-CoV infection using RT2 Profiler PCR Arrays. We also quantified the expression level of primary inflammatory cytokines/chemokines. Our results showed a downregulation of Th2, inadequate (partial) Th1 immune response and high expression levels of inflammatory cytokines IL-1α and IL-1β and the neutrophil chemoattractant chemokine IL-8 (CXCL8) in the lower respiratory tract of MERS-CoV infected patients. Moreover, we identified a high viral load in all included patients. We also observed a correlation between inflammatory cytokines, Th1, and Th2 downregulation and the case fatality rate. Th1 and Th2 response downregulation, high expression of inflammatory cytokines, and high viral load may contribute to lung inflammation, severe infection, the evolution of pneumonia and ARDS, and a higher case fatality rate. Further study of the molecular mechanisms underlying the Th1 and Th2 regulatory pathways will be vital for active vaccine development and the identification of novel therapeutic strategies.


The impact of H1N1 influenza A virus pandemic on the emergency medical service in Kobe


Antibody-mediated targeting of viral vectors to the Fc receptor expressed on acute myeloid leukemia cells


title: Inhibition of murine coronavirus RNA synthesis by hydroxyguanidine derivatives

text: Abstract A series of hydroxyguanidine derivatives, which are substituted salicylaldehyde Schiff-bases of 1-amino-3- hydroxyguanidine tosylate, were tested for the inhibition of RNA synthesis of mouse hepatitis virus (MHV). It was shown that these compounds could selectively inhibit virus-specific RNA synthesis. Every aspect of viral RNA synthesis, including synthesis of negative-stranded RNA, subgenomic mRNA transcription and genomic RNA replication, was inhibited to roughly the same extent. These compounds are the first known inhibitors of coronaviral RNA synthesis and should prove useful for understanding the mechanism of viral RNA synthesis.


title: Syndrome respiratoire aigu sévère : une épidémie singulière de pneumonie virale

text: Résumé Agent infectieux Le Syndrome respiratoire aigu sévère (Sras) est une pneumopathie fébrile initialement observée en Chine à la fin de l’année 2002. L’agent infectieux étiologique a rapidement été identifié comme étant un nouveau Coronavirus, baptisé Coronavirus associé au Sras (Sras-CoV). La transmission du virus est interhumaine, par les particules respiratoires principalement. Clinique et traitement La gravité clinique est variable, allant de la simple fièvre au syndrome de détresse respiratoire aigu. Il n’existe pas de traitement spécifique. Cependant, la ribavirine combinée à des corticoïdes a été utilisée avec succès dans un certain nombre de cas. Épidémiologie Au cours du premier semestre de l’année 2003, la dissémination du virus a été extrêmement rapide, évoluant sur un mode pandémique, contaminant plus de 8000 patients, dont 774 en sont décédés. Le réservoir viral, probablement d’origine animale, reste inconnu à ce jour. L’épidémie semble être actuellement jugulée, mais des ré-émergences sporadiques ou épidémiques sont possibles et ont été décrites en Chine dans la province de Guangdong début janvier 2004. Summary Infectious agent The severe acute respiratory syndrome (SARS) is a febrile pneumonia initially observed in China at the end of 2002. The infectious agent has rapidly been identified as a new coronavirus, baptised SARS-associated coronavirus (CoV-SARS). Transmission is inter-human, via respiratory particles mainly. Clinical presentation and treatment The clinical presentation is highly variable, from a mild fever to an acute respiratory distress syndrome. There is no specific treatment. Ribavirin associated with steroids have been used with success in numerous cases. Epidemiology During the first half of 2003, the spreading of the virus has been very fast, with a pandemic mode of evolution. More than 8 000 people were infected and 774 died. The reservoir of the virus, which may be animal, is still unknown. The epidemic seems to be controlled, but sporadic or epidemic re-emergences may occur and have been observed in China duting January 2004.


docid: quoirwcm

title: Proceedings of the Annual Meeting of the American Rheumatism Association


Hydroxychloroquine as Prophylaxis for Coronavirus SARS-CoV-2 Infection: Review ff the Ongoing Clinical Trials


title: Design, synthesis, antiviral and cytostatic evaluation of novel isoxazolidine nucleotide analogues with a 1,2,3-triazole linker

text: Azidation (TMSN(3), SnCl(4)) of a 9:1 mixture of trans- and cis-5-acetoxy-2-methylisoxazolidin-3-yl-3-phosphonates at the anomeric carbon atom led to the formation of the equimolar mixture of cis- and trans-5-azido-2-methylisoxazolidin-3-yl-3-phosphonates, which were efficiently separated. The 1,3-dipolar cycloaddition of pure trans- and cis-5-azidoisoxazolidin-3-yl-3-phosphonates with selected alkynes gave the respective nucleoside mimetics containing a 1,2,3-triazole linker. The (1,2,3-triazolyl)isoxazolidine phosphonates obtained herein were evaluated in vitro for activity against a variety of DNA and RNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. Compounds 15f–j and 16f–j were cytostatic in the higher micromolar range.


title: Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection

text: Mitochondria- as well as p53-based signaling pathways are central for the execution of the intrinsic apoptotic cascade. Their contribution to rubella virus (RV)-induced apoptosis was addressed through time-specific evaluation of characteristic parameters such as permeabilization of the mitochondrial membrane and subsequent release of the pro-apoptotic proteins apoptosis-inducing factor (AIF) and cytochrome c from mitochondria. Additionally, expression and localization pattern of p53 and selected members of the multifunctional and stress-inducible cyclophilin family were examined. The application of pifithrin μ as an inhibitor of p53 shuttling to mitochondria reduced RV-induced cell death to an extent similar to that of the broad spectrum caspase inhibitor z-VAD-fmk (benzyloxycarbonyl-V-A-D-(OMe)-fmk). However, RV progeny generation was not altered. This indicates that, despite an increased survival rate of its cellular host, induction of apoptosis neither supports nor restricts RV replication. Moreover, some of the examined apoptotic markers were affected in a strain-specific manner and differed between the cell culture-adapted strains: Therien and the HPV77 vaccine on the one hand, and a clinical isolate on the other. In summary, the results presented indicate that the transcription-independent mitochondrial p53 program contributes to RV-induced apoptosis.


title: First report on natural infection with Leishmania infantum in a domestic ferret (Mustela putorius furo) in Spain

text: Abstract A pet domestic ferret (Mustela putorius furo) with a papular lesion involving the right pinna was diagnosed with chronic pyogranulomatous dermatitis by histopathologic examination. Intralesional, intracytoplasmic oval microorganisms compatible with Leishmania spp. or Histoplasma spp. were observed in macrophages and multinucleate giant cells. Leishmania infantum (L. infantum) infection was diagnosed by PCR, culture in Novy-MacNeal-Nicolle medium, and immunohistochemistry. Abnormal clinicopathological results included increased alanine transferase, alkaline phosphatase, serum gamma glutamyl transferase and polyclonal gammpathy. Anti-Leishmania antibodies were detected by enzyme-linked immunosorbent assay, immunofluorescence antibody test and western blot using L. infantum antigen. Immunoreactivity against the 16 kDa specific L. infantum antigen fraction was observed by western blot. PCR performed in blood samples obtained from this patient after positive parasite isolation detected L. infantum DNA. To the authors' knowledge, this is the first diagnosis and isolation of L. infantum in a domestic ferret naturally infected in an endemic region (Spain) where canine and feline leishmaniosis is frequently detected. According to these findings, ferrets should be included as potential reservoir hosts of L. infantum. Future investigations should analyze the epidemiological role of ferrets in L. infantum infection including the prevalence of infection.


docid: umyxscxn

title: On Viruses, Discovery, and Recognition

text: This year's Nobel Prize in Physiology or Medicine rewards the discoverers of two viruses that cause major afflictions of humankind. Identifying human papilloma virus (HPV) and human immunodeficiency virus (HIV) might now appear to have been simple, but the way forward was far from obvious at the time.


title: Strengths and Weaknesses of FDA-Approved/Cleared Diagnostic Devices for the Molecular Detection of Respiratory Pathogens

text: The rapid, sensitive, and specific identification of the microbial etiological characteristics of respiratory tract infections enhances the appropriate use of both antibiotics and antiviral agents and reduces the risk of nosocomial transmission. This article reviews the current nucleic acid amplification tests approved by the U.S. Food and Drug Administration (FDA) for the detection of respiratory pathogens. In addition, Emergency Use Authorization tests for the detection of 2009 influenza A H1N1 are discussed. The advantages and limitations of the current FDA-approved/cleared tests are reviewed.


docid: lwyeqqvy

title: Optimal Data Transmission Strategy for Healthcare-Based Wireless Sensor Networks: A Stochastic Differential Game Approach

text: As the development of information and communication technology (ICT) and the affirmation of the importance of healthcare, using wireless sensor networks (WSNs) is a promising approach to assist modern medical practices. The transmission optimization of HWSNs is an issue worth studying deeply, which is facing challenges such as data diversity, real-time requirement, reliable transmission, dynamic environment and so on. This paper considers four kinds of transmission cost comprehensively, and adopts the stochastic differential game theory to discuss this issue. With the objective of minimizing the transmission cost, three kinds of game models are constructed, i.e., cooperative model, partial cooperative model and non-cooperative model. The optimal transmission strategies under different game modes are obtained for HWSNs. The numerical simulation compares three strategies and verifies the validity of the method present in this paper.


Chemical Constituents of the Plants of the Genus Calophyllum


title: Antiviral activity of silymarin against chikungunya virus

text: The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.


docid: jmzjfwxi

title: ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19

text: Smokers and individuals with COPD have increased airway expression of ACE-2, which is the entry receptor for the COVID-19 virus. This may explain the increased risk of severe COVID-19 in these subpopulations and highlight importance of smoking cessation.


title: Identifying relationships among acute phase proteins (haptoglobin, serum amyloid A, fibrinogen, ceruloplasmin) and clinical findings in dairy calf diarrhea

text: The acute phase response is a nonspecific inflammatory reaction of the host that occurs shortly after any tissue injury. The response includes changes in the concentration of plasma proteins called acute phase proteins (APPs). Calf diarrhea is an important disease that occurs in association with the interaction of various infectious agents and calf susceptibility. The economic losses is associated with death loss and treatment costs, reduction of live weight gain, and reduction of productive life span, which may be considerable. The aim of the present study was to identify relationships among APPs in calves with diarrhea in the different clinical features. Holstein calves (50) within 1 day to 4 months old with signs of diarrhea and healthy calves (40) with similar age and sex were selected. Standard clinical examinations and also dehydration degree were carried out on each calf and were recorded. Calves with clinical signs of diarrhea were divided in different groups based on the severity of the clinical findings, fever and degree of dehydration. Blood samples were taken from the jugular vein from all calves into vacutainers containing ethylenediaminetetraacetic acid (EDTA) for separating plasma and without EDTA for serum biochemical analysis. APP [haptoglobin (Hp), serum amyloid A (SAA), fibrinogen (Fib), and ceruloplasmin (Cp)] concentrations were measured using validated standard methods. The results indicated a significant increases in APPs in diarrheic calves which was most obvious in Hp and SAA (P < 0.001). Calves with severe clinical signs of diarrhea had a significant increases in their Hp and SAA (P < 0.001) compared to calves with moderate or without systemic clinical signs. Diarrheic calves with fever compared to diarrheic calves without fever had a significant increases in their Hp and SAA (P < 0.01). Also, diarrheic calves with severe dehydration compared to diarrheic calves with mild and moderate dehydration had significant increases in Hp and SAA (P < 0.05), and these parameters (Hp, SAA, Fib, and Cp) among calves with mild and moderate dehydration had no significant changes. Our results indicated that monitoring the APP responses in diarrheic calves with different clinical signs could be useful as prognostic tools and facilitate treatment decisions.


title: Impact of Influenza on Outpatient Visits, Hospitalizations, and Deaths by Using a Time Series Poisson Generalized Additive Model

text: BACKGROUND: The disease burden associated with influenza in developing tropical and subtropical countries is poorly understood owing to the lack of a comprehensive disease surveillance system and information-exchange mechanisms. The impact of influenza on outpatient visits, hospital admissions, and deaths has not been fully demonstrated to date in south China. METHODS: A time series Poisson generalized additive model was used to quantitatively assess influenza-like illness (ILI) and influenza disease burden by using influenza surveillance data in Zhuhai City from 2007 to 2009, combined with the outpatient, inpatient, and respiratory disease mortality data of the same period. RESULTS: The influenza activity in Zhuhai City demonstrated a typical subtropical seasonal pattern; however, each influenza virus subtype showed a specific transmission variation. The weekly ILI case number and virus isolation rate had a very close positive correlation (r = 0.774, P < 0.0001). The impact of ILI and influenza on weekly outpatient visits was statistically significant (P < 0.05). We determined that 10.7% of outpatient visits were associated with ILI and 1.88% were associated with influenza. ILI also had a significant influence on the hospitalization rates (P < 0.05), but mainly in populations <25 years of age. No statistically significant effect of influenza on hospital admissions was found (P > 0.05). The impact of ILI on chronic obstructive pulmonary disease (COPD) was most significant (P < 0.05), with 33.1% of COPD-related deaths being attributable to ILI. The impact of influenza on the mortality rate requires further evaluation. CONCLUSIONS: ILI is a feasible indicator of influenza activity. Both ILI and influenza have a large impact on outpatient visits. Although ILI affects the number of hospital admissions and deaths, we found no consistent influence of influenza, which requires further assessment.


Probiotics and COVID-19


No-Test Medication Abortion: A Sample Protocol for Increasing Access During a Pandemic and Beyond


title: Reservoirs of Porcine Circoviruses: A Mini Review

text: Porcine circovirus (PCV) is one of the smallest known DNA viruses in mammals. At present, PCVs are divided into three species, PCV1, PCV2, and PCV3. PCV1 and PCV2 were found in the 1970s and the 1990s, respectively, whereas PCV3 was discovered recently in 2016. PCV1 does not cause diseases in pigs. However, PCV3, similar to PCV2, is reported to be associated with several swine diseases, including porcine dermatitis and nephropathy syndrome (PDNS) and reproductive failure. PCVs are very common in domestic pigs as well as wild boars. However, PCVs have been occasionally isolated from non-porcine animals, including ruminants (such as cattle, goats, wild chamois, and roe deers), rodents (such as NMRI mice, BALB/c mice, Black C57 mice, ICR mice, Mus musculus, and Rattus rattus), canines (such as dogs, minks, foxes, and raccoon dogs), insects (such as flies, mosquitoes, and ticks), and shellfish. Moreover, PCVs are frequently reported in biological products, including human vaccines, animal vaccines, porcine-derived commercial pepsin products, and many cell lines. PCVs are also abundant in the environment, including water samples and air samples. Interestingly, PCV1 and/or PCV2 antibody or antigen has also been detected in sera, stool samples and respiratory swab samples of human, revealing zoonotic potential of PCVs. Thus, PCVs inhabit many types of reservoirs. In this review, we summarize the reservoirs of PCVs, and this information would be helpful in understanding the natural circulating status and possible cross-species transmission of PCVs.


title: Studies on nitric oxide synthase activity in haemocytes of shrimps Fenneropenaeus chinensis and Marsupenaeus japonicus after white spot syndrome virus infection

text: Abstract The nitric oxide synthase (NOS) activity in the haemocytes of shrimps Fenneropenaeus chinensis (Osbeck) and Marsupenaeus japonicus (Bate) was studied after white spot syndrome virus (WSSV) infection to determine its characteristics in response to virus infection. First, the NOS activity in haemocytes of shrimps was determined by the means of NBT reduction and changes in cell conformation. And the variations of NOS activity in shrimps after challenge with WSSV intramuscularly were evaluated through the analysis of l-citrulline and total nitrite/nitrate (both as NO derivates) concentrations. The result showed that NOS activity in the haemocytes of F. chinensis increased slightly from 0 to 12h postchallenge, indicated by the variations of l-citrulline (from 11.15±0.10 to 12.08±0.64μM) and total nitrite/nitrate concentrations (from 10.45±0.65 to 12.67±0.52μM). Then it decreased sharply till the end of the experiment (84h postchallenge), the concentrations of l-citrulline and total nitrite/nitrate at 84h were 1.58±0.24 and 2.69±0.70μM, respectively. The LPS-stimulated NOS activity kept constant during the experiment. However, in M. japonicus, the NOS activity kept increasing during the first 72h postchallenge, the concentrations of l-citrulline and total nitrite/nitrate increased from 7.82±0.77 at 0h to 10.79±0.50μM at 72h, and from 8.98±0.43 at 0h to 11.20±0.37μM at 72h, respectively. Then it decreased till the end of the experiment (216h postchallenge), and the concentrations of l-citrulline and total nitrite/nitrate at 216h were 5.66±0.27 and 4.68±0.16μM, respectively. More importantly, an apparent increase of LPS-stimulated NOS activity was observed in M. japonicus at 48h postchallenge, which was about 4 times higher than that in the control group of health shrimps. In correspondence with the difference of NOS activity between the two species of shrimps, the cumulative mortalities of the shrimps were also different. All shrimps of F. chinensis in the mortality experiment died in 66h, much more quickly than M. japonicus, whose accumulative mortality reached 100% after 240h. Data here reported let us hypothesize that NOS activity in the haemocytes of shrimps F. chinensis and M. japonicus responses to WSSV infection differently, and this might be one of the reasons for the different susceptibility of F. chinensis and M. japonicus to WSSV infection.


title: siRNA and the lung: research tool or therapeutic drug?

text: Oligonucleotide-based therapeutics have been hailed as ‘the next great wave of the biotechnology revolution’ starting with antisense oligonucleotides (ASOs) nearly 20 years ago to RNA interference (RNAi) currently. Is RNAi just the latest research tool or does it have real potential as a therapeutic drug modality? As a research tool, it is evident that RNAi has revolutionized the biological sciences by allowing selective silencing of messenger RNA (mRNA) expression. With the advent of the postgenomic era, RNAi offers a therapeutic platform on which to identify potential picomolar active drug candidates to any target, including those that are conventionally undruggable. In this review, we will discuss the progress made in developing RNAi therapeutics for the treatment of respiratory diseases.


title: Tmprss2 Is Essential for Influenza H1N1 Virus Pathogenesis in Mice

text: Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.


title: Oral Recombinant Feline Interferon-Omega as an alternative immune modulation therapy in FIV positive cats: Clinical and laboratory evaluation

text: Abstract Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1MU/cat rFeIFN-ω PO, SID, 90days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP’s variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol.


Recommendations for Surgery During the COVID-19 Pandemic


Human Enteric Coronaviruses: Further Characterization and Immunoblotting of Viral Proteins


title: Pathogenicity and immunogenicity of a new strain of porcine epidemic diarrhea virus containing a novel deletion in the N gene

text: Abstract Since late 2010, highly virulent PEDV G2-genotype strains have emerged globally extracting heavy losses on the pork industries of numerous countries. We investigated the characteristics of a field strain of PEDV (PEDV strain SH) isolated from a piglet with severe diarrhea on a farm in Shanghai China. Whole genome sequencing and analysis revealed that the SH strain belonged to subtype G2b and has a unique 12-aa deletion (aa 399–410) including the antigenic epitope NEP-1C9 (aa 398–406) of the N protein. PEDV SH strain is highly pathogenic to challenged newborn piglets, resulting in 100 % morbidity and mortality. Pathological examination revealed significant villus atrophy in the jejuna of infected piglets. Mice inoculated with inactivated PEDV SH produced antibodies against the N protein, but no antibodies against the deletions. These results illustrated that deletion of the NEP-1C9 epitope had no effect on the immunogenicity or pathogenicity of PEDV, providing evidence of the necessity to monitor the genetic diversity of the virus. Our study also contributes to development of candidate for vaccines and diagnostics that could differentiate pigs seropositive due to vaccination by conventional strains from wild virus infection.


docid: azdpkkbh

title: Interleukin-1 (type II) receptor expression in normal and pathological human brain


title: Managing common endocrine disorders amid COVID-19 pandemic

text: BACKGROUND AND AIMS: The novel coronavirus disease (COVID-19) pandemic and the resulting nationwide lockdowns have posed a major challenge to the management of pre-existing and newly diagnosed endocrine disorders. Herein, we have summarized the management approaches of common endocrine disorders amid the ongoing pandemic. METHODS: We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till 25 May 2020, with the following keywords: “COVID-19”, “diabetes mellitus”, “thyroid disorders”, “primary adrenal insufficiency”, “Cushing's syndrome”, “pituitary tumors”, “vitamin D″, “osteoporosis”, “primary hyperparathyroidism”, “hypoparathyroidism”, “management”, “treatment” and “guidelines” with interposition of the Boolean operator “AND”. RESULTS: We have summarized the feasible strategies for the management of diabetes mellitus, hypothyroidism, hyperthyroidism, primary adrenal insufficiency (including congenital adrenal hyperplasia), Cushing's syndrome, pituitary tumors, osteoporosis, primary hyperparathyroidism and hypoparathyroidism amid the constraints laid down by the raging pandemic. In general, medical management should be encouraged and surgical interventions should be deferred whenever possible. Ongoing medications should be continued. Sick-day rules should be sincerely adhered to. Regular contact with physicians can be maintained through teleconsultations and virtual clinics. CONCLUSIONS: Considering the burden of endocrine disorders in the general population, their management needs to be prioritized amid the ongoing COVID-19 pandemic.


title: AGS Position Statement: Resource Allocation Strategies and Age‐Related Considerations in the COVID‐19 Era and Beyond

text: COVID‐19 continues to impact older adults disproportionately, from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these needs have focused attention on how resources are ultimately allocated and used. Some strategies misguidedly use age as an arbitrary criterion, which inappropriately disfavors older adults. This statement represents the official policy position of the American Geriatrics Society (AGS). It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations to consider when developing strategies for allocating scarce resources during an emergency involving older adults. Members of the AGS Ethics Committee collaborated with interprofessional experts in ethics, law, nursing, and medicine (including geriatrics, palliative care, emergency medicine, and pulmonology/critical care) to conduct a structured literature review and examine relevant reports. The resulting recommendations defend a particular view of distributive justice that maximizes relevant clinical factors and de‐emphasizes or eliminates factors placing arbitrary, disproportionate weight on advanced age. The AGS positions include: (1) avoiding age per se as a means for excluding anyone from care; (2) assessing comorbidities and considering the disparate impact of social determinants of health; (3) encouraging decision makers to focus primarily on potential short‐term (not long‐term) outcomes; (4) avoiding ancillary criteria such as “life‐years saved” and “long‐term predicted life expectancy” that might disadvantage older people; (5) forming and staffing triage committees tasked with allocating scarce resources; (6) developing institutional resource allocation strategies that are transparent and applied uniformly; and (7) facilitating appropriate advance care planning. The statement includes recommendations that should be immediately implemented to address resource allocation strategies during COVID‐19, aligning with AGS positions. The statement also includes recommendations for post‐pandemic review. Such review would support revised strategies to ensure that governments and institutions have equitable emergency resource allocation strategies, avoid future discriminatory language and practice, and have appropriate guidance to develop national frameworks for emergent resource allocation decisions.


title: The impact of COVID-19 pandemic on surgical residency programmes in Italy: a nationwide analysis on behalf of the Italian Polyspecialistic Young Surgeons Society (SPIGC)

text: INTRODUCTION: Recently, Italy has been heavily hit by COVID-19 pandemic and today it is still one of the most affected countries in the world. The subsequent necessary lockdown decreed by the Italian Government had an outstanding impact on the daily life of the entire population, including that of Italian surgical residents’ activity. Our survey aims to evaluate the impact of COVID-19 on the training programme of Italian surgical residents. MATERIALS AND METHODS: We designed a 12-item-electronic anonymous questionnaire on SurveyMonkey© web application. The survey was composed of different sections concerning demographic characteristics and impacts of COVID-19 on the concrete participation in clinical, surgical and research activities. Future perspectives of responders after the pandemic were also investigated. RESULTS: Eighty hundred responses were collected, and 756 questionnaires were considered eligible to be included in the study analysis. Almost 35 and 27% of respondents experienced, respectively, complete interruption of surgical and clinical activities. A subgroup analysis, comparing the COVID-19 impact on clinical activities with demographics data, showed a statistically significant difference related to specialties (p = 0.0062) and Italian regions (p < 0.0001). Moreover, 112 residents have been moved to non-surgical units dealing with COVID-19 or, in some case, they voluntarily decided to interrupt their residency programme to support the ongoing emergency. CONCLUSION: Our survey demonstrated that COVID-19 pandemic has severely impacted the educational programme of Italian surgical residents. Despite many regional differences, this survey highlighted the overall shortage of planning in the re-allocation of resources facing this unexpected health emergency. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13304-020-00811-9) contains supplementary material, which is available to authorized users.


title: VAPiD: a lightweight cross platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank

text: With sequencing technologies becoming cheaper and easier to use, more groups are able to obtain whole genome sequences of viruses of public health and scientific importance. Submission of genomic data to NCBI GenBank is a requirement prior to publication and plays a critical role in making scientific data publicly available. GenBank currently has automatic prokaryotic and eukaryotic genome annotation pipelines but has no viral annotation pipeline beyond influenza virus. Annotation and submission of viral genome sequence is a non-trivial task, especially for groups that do not routinely interact with GenBank for data submissions. We present Viral Annotation Pipeline and iDentification (VAPiD), a portable and lightweight command-line tool for annotation and GenBank deposition of viral genomes. VAPiD supports annotation of nearly all unsegmented viral genomes. The pipeline has been validated on human immunodeficiency virus, human parainfluenza virus 1-4, human metapneumovirus, human coronaviruses (229E/OC43/NL63/HKU1/SARS/MERS), human enteroviruses/rhinoviruses, measles virus, mumps virus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human polyomaviruses BK/JC/MCV, human adenoviruses, and human papillomaviruses. The program can handle individual or batch submissions of different viruses to GenBank and correctly annotates multiple viruses, including those that contain ribosomal slippage or RNA editing without prior knowledge of the virus to be annotated. VAPiD is programmed in Python and is compatible with Windows, Linux, and Mac OS systems. We have created a portable, lightweight, user-friendly, internet-enabled, open-source, command-line genome annotation and submission package to facilitate virus genome submissions to NCBI GenBank. Instructions for downloading and installing VAPiD can be found at https://github.com/rcs333/VAPiD.


title: Biological and Epidemiological Trends in the Prevalence and Mortality due to Outbreaks of Novel Coronavirus COVID-19

text: Abstract The novel coronavirus (Covid-19) infection outbreak has posed a major threat to international health system and economy. This study is aimed at investigating the biological and epidemiological trends in the prevalence and mortality due to outbreaks of novel coronavirus (COVID-19) infections. The data on the global outbreak of COVID-19, were obtained from World Health Organization (WHO), Worldometer, Centers for Disease Control and Prevention (CDC), and research institutes. The information was also recorded from research documents published in global scientific journals indexed in Pub Med and Institute of Scientific Information (ISI) Web of Science on the trends in the prevalence and mortality due to COVID-19 infection outbreaks. The results show rising trends in the transmission, prevalence and mortality rate due to coronavirus COVID-19. During the period of December 29, 2019 through March 31, 2020, it has infected 750890 people worldwide, resulting in 36405 deaths with a mortality rate of 4.84%. The infections were more frequent among male gender with above 60 years of age. The mean growth rate index for total number of cases from January 23 to March 31, 2020 was 1.20 and growth rate index for mortality rate was 1.12. There was a positive association between the prevalence and mortality rate (R2=0.996). The novel coronavirus COVID-19 is highly contagious and has affected a large number of people worldwide. It is still spreading with mutable prevalence and mortality outbreak trends. The global health officials have taken priority measures to prevent the further outbreaks of this emerging pathogen across the globe. However, the rising number of cases and mortality risk estimates are demonstrating that enhanced public health mediations, good hygienic conditions, social distancing and movement limitations may control the COVID-19 epidemics.


title: Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents

text: Abstract Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8+ lymphocytes and NK cells were significantly reduced in cases of severe infection compared to patients with mild infection and healthy individuals. The NK group 2 member A (NKG2A) receptor transduces inhibitory signalling, suppressing NK cytokine secretion and cytotoxicity. Overexpression of NKG2A has been observed on CD8+ and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8+ cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8+ cells and NK cells in cancers modulated tumor growth, restoring CD8+ T and NK cell function. A recently proposed mechanism via which SARS-CoV-2 overrides innate immune response of the host is by over-expressing NKG2A on CD+ T and NK cells, culminating in functional exhaustion of the immune response against the viral pathogen. Monalizumab is an inhibiting antibody against NKG2A which can restore the function of CD8 + T and NK cells in cancers, successfully ceasing tumor progression with no significant side effects in Phase 2 clinical trials. We hypothesize that patients with severe COVID-19 have a severely compromised innate immune response and could be treated via the use of Monalizumab, interferon α, chloroquine, and other antiviral agents.


SARS-CoV-2: the emergence of a viral pathogen causing havoc on human existence


title: Allogeneic cardiosphere-derived cells (CAP-1002) in critically ill COVID-19 patients: compassionate-use case series

text: There are no definitive therapies for patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Therefore, new therapeutic strategies are needed to improve clinical outcomes, particularly in patients with severe disease. This case series explores the safety and effectiveness of intravenous allogeneic cardiosphere-derived cells (CDCs), formulated as CAP-1002, in critically ill patients with confirmed coronavirus disease 2019 (COVID-19). Adverse reactions to CAP-1002, clinical status on the World Health Organization (WHO) ordinal scale, and changes in pro-inflammatory biomarkers and leukocyte counts were analyzed. All patients (n = 6; age range 19–75 years, 1 female) required ventilatory support (invasive mechanical ventilation, n = 5) with PaO(2)/FiO(2) ranging from 69 to 198. No adverse events related to CAP-1002 administration were observed. Four patients (67%) were weaned from respiratory support and discharged from the hospital. One patient remains mechanically ventilated as of April 28th, 2020; all survive. A contemporaneous control group of critically ill COVID-19 patients (n = 34) at our institution showed 18% overall mortality at a similar stage of hospitalization. Ferritin was elevated in all patients at baseline (range of all patients 605.43–2991.52 ng/ml) and decreased in 5/6 patients (range of all patients 252.89–1029.90 ng/ml). Absolute lymphocyte counts were low in 5/6 patients at baseline (range 0.26–0.82 × 10(3)/µl) but had increased in three of these five patients at last follow-up (range 0.23–1.02 × 10(3)/µl). In this series of six critically ill COVID-19 patients, intravenous infusion of CAP-1002 was well tolerated and associated with resolution of critical illness in 4 patients. This series demonstrates the apparent safety of CAP-1002 in COVID-19. While this initial experience is promising, efficacy will need to be further assessed in a randomized controlled trial.