title: Emerging and Zoonotic Infections in Women

text: Emerging infections, many of them zoonotic, are caused by a wide variety of pathogens with global distribution. Their impact on women is similarly diverse. Pathogens that were previously rare are emerging in recent years to cause disease in new populations, and global travel facilitates their rapid spread across continents. Finally, human encroachment on previously remote areas has brought people into contact with zoonotic diseases and vectors never before characterized. Although systematic study of rare outbreaks can be challenging, our knowledge of emerging pathogens and their differential effects on women, including those who are pregnant, has started to accumulate. We discuss the effects on women of lymphocytic choriomeningitis virus, West Nile virus, SARS coronavirus, avian influenza A (H5N1), virus, and the viral hemorrhagic fevers. We also explore the spirochetal illnesses and Chagas disease as they pertain to the pregnant patient. Finally, we review the potential impact of candidate bioterror agents on the female population, and address related issues of prophylaxis and therapy.


title: An extended outbreak of infectious peritonitis in a closed colony of european wildcats (Felis silvestris)

text: Summary Feline infectious peritonitis is a multisystemic disease of domestic and exotic cats caused by a coronavirus. An outbreak of feline infectious peritonitis was investigated in a closed colony of European wildcats (Felis silvestris) at a zoological garden. Over a six-year period, a putative fading kitten syndrome occurred in six of 11 litters born and severe lesions of infectious peritonitis occurred in five of the eight wildcats retained in the colony during this period. Lesions were more acute in the early stages of the outbreak and included perivascular pyogranulomatous inflammation with exudative serositis. Lesions occurred only in males. Vascular lesions were common in the liver of all affected wildcats, serositis occurred in the abdominal and thoracic cavities in most cases and meningeal lesions were present in two cases. Immunohistochemistry with specific antisera detected viral antigen within macrophages in all lesions. This outbreak demonstrates that the lesions of feline infectious peritonitis can become modified over time and that the virus can persist in a closed colony, possibly via carrier wildcats.


title: Natural and artificial hyperimmune solutions: Impact on health in puppies

text: Colostrum and milk are complex mammary secretions providing the puppy with many nutritional and immunological factors, which play a crucial role for its correct development and survival. In the case of colostrum and/or milk intake deficiency, puppies are at increased risk of infectious diseases. This work reviews the various nutritional hyperimmune supplementations proposed to provide a passive immune protection and to positively impact puppies’ health. Some strategies rely on canine immunoglobulins: canine colostrum banking and canine serum/plasma supplementation. Others involve heterologous sources of antibodies and other immune factors: bovine colostrum or hyperimmune egg powder. Among the different solutions evaluated from birth to weaning, canine plasma and hyperimmune egg powder showed promising beneficial effect on puppies’ health. Canine plasma seems to positively impact not only growth (increased growth during the neonatal period), but also digestive health (higher species richness of intestinal microbiota) and the general health (tendency of lower morbidity). Puppies supplemented with hyperimmune egg powder presented increased neonatal growth and decreased risk of canine parvovirus infection. Nevertheless, natural canine maternal colostrum and milk ingestion remains the optimal guarantee for puppies’ health and survival, as a source of immunity, energy and growth factors.


title: Infecciones neonatales (II)

text: Resumen Las infecciones neonatales son un problema de salud pública mundial. Su incidencia se aproxima al 1 % de los nacimientos en los países industrializados, pero es más elevada en los países en desarrollo. En 1996, las infecciones aparecidas en el primer mes de vida eran responsables de cinco millones de fallecimientos anuales. Casi todos los microorganismos patógenos (bacterias, hongos y virus) pueden ser causantes de infecciones en el recién nacido. La epidemiología bacteriana varía según las épocas, los países e incluso las regiones, lo que impide extrapolar las propuestas terapéuticas formuladas a partir de la expenencia de un centro, tanto en lo que se refiere a los protocolos curativos como a los preventivos.


title: Coronavirus disease 2019: initial chest CT findings

text: OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20–91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4–7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: • Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. • The halo sign may be a special CT feature in the early-stage COVID-19 patients. • Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.


title: Severe respiratory SARS-CoV2 infection: Does ACE2 receptor matter?

text: Abstract SARS-CoV-2 is a novel virus of the Coronaviridiae family that represents a major global health issue. Mechanisms implicated in virus/host cells interaction are central for cell infection and replication that in turn lead to disease onset and local damage. To enter airway and lung epithelia, SARS-CoV-2 attaches to ACE2 receptors by spike (S) glycoproteins. Molecular mechanisms that promote interaction between SARS-CoV-2 virus and host with particular focus on virus cell entry receptor ACE2 are described. We further explore the impact of underlying medical conditions and therapies including renin-angiotensin inhibitors on modulating ACE 2, which is the major SARS-CoV-2 cell entry receptor.


title: Complete genome sequence of Treponema pallidum ssp. pallidum strain SS14 determined with oligonucleotide arrays

text: BACKGROUND: Syphilis spirochete Treponema pallidum ssp. pallidum remains the enigmatic pathogen, since no virulence factors have been identified and the pathogenesis of the disease is poorly understood. Increasing rates of new syphilis cases per year have been observed recently. RESULTS: The genome of the SS14 strain was sequenced to high accuracy by an oligonucleotide array strategy requiring hybridization to only three arrays (Comparative Genome Sequencing, CGS). Gaps in the resulting sequence were filled with targeted dideoxy-terminators (DDT) sequencing and the sequence was confirmed by whole genome fingerprinting (WGF). When compared to the Nichols strain, 327 single nucleotide substitutions (224 transitions, 103 transversions), 14 deletions, and 18 insertions were found. On the proteome level, the highest frequency of amino acid-altering substitution polymorphisms was in novel genes, while the lowest was in housekeeping genes, as expected by their evolutionary conservation. Evidence was also found for hypervariable regions and multiple regions showing intrastrain heterogeneity in the T. pallidum chromosome. CONCLUSION: The observed genetic changes do not have influence on the ability of Treponema pallidum to cause syphilitic infection, since both SS14 and Nichols are virulent in rabbit. However, this is the first assessment of the degree of variation between the two syphilis pathogens and paves the way for phylogenetic studies of this fascinating organism.


title: Emerging Trends in Clinical Tropical Medicine Research

text: The American Society for Tropical Medicine and Hygiene recently inaugurated an award for the best clinical research article published in the society’s journal in the previous year. This article summarizes both the process of selecting the winner and several themes that stood out in those articles which rose to the top for consideration. Themes of note included the importance of doing clinical research outside of referral centers, the complexity that must be considered when implementing interventions, incorporation of both ends of the age spectrum into studies, and considering cost-effectiveness and opportunity cost of interventions.


title: Transport and deposition of hygroscopic particles in asthmatic subjects with and without airway narrowing

text: Abstract This study numerically investigates the effect of hygroscopicity on transport and deposition of particles in severe asthmatic lungs with distinct airway structures. The study human subjects were selected from two imaging-based severe asthmatic clusters with one characterized by non-constricted airways and the other by constricted airways in the lower left lobe (LLL). We compared the deposition fractions of sodium chloride (NaCl) particles with a range of aerodynamic diameters (1–8 μm) in cluster archetypes under conditions with and without hygroscopic growth. The temperature and water vapor distributions in the airways were simulated with an airway wall boundary condition that accounts for variable temperature and water vapor evaporation at the interface between the lumen and the airway surface liquid layer. On average, the deposition fraction increased by about 6% due to hygroscopic particle growth in the cluster subjects with constricted airways, while it increased by only about 0.5% in those with non-constricted airways. The effect of particle growth was most significant for particles with an initial diameter of 2 μm in the cluster subjects with constricted airways. The effect diminished with increasing particle size, especially for particles with an initial diameter larger than 4 μm. This suggests the necessity to differentiate asthmatic subjects by cluster in engineering the aerosol size for tailored treatment. Specifically, the treatment of severe asthmatic subjects who have constricted airways with inhalation aerosols may need submicron-sized hygroscopic particles to compensate for particle growth, if one targets for delivering to the peripheral region. These results could potentially inform the choice of particle size for inhalational drug delivery in a cluster-specific manner.


title: Point‐of‐care diagnostic assay for rapid detection of porcine deltacoronavirus using the recombinase polymerase amplification method

text: Porcine deltacoronavirus (PDCoV) has emerged and spread throughout the porcine industry in many countries over the last 6 years. PDCoV caused watery diarrhoea, vomiting and dehydration in newborn piglets. A sensitive diagnostic method would be beneficial to the prevention and control of PDCoV infection. Recombinase polymerase amplification (RPA) is an isothermal amplification method which has been widely used for virus detection. A probe‐based reverse transcription RPA (RT‐RPA) assay was developed for real‐time detection of PDCoV. The amplification can be finished in 20 min and fluorescence monitoring was performed by a portable device. The lowest detection limit of the PDCoV RT‐RPA assay was 100 copies of RNA molecules per reaction; moreover, the RT‐RPA assay had no cross‐reaction with other common swine viruses. The clinical performance of the RT‐RPA assay was evaluated using 108 clinical samples (54 intestine specimens and 54 faecal swab specimens). The coincidence rate of the detection results for clinical samples between RT‐RPA and RT‐qPCR was 97.2%. In summary, the real‐time RT‐RPA assay offers a promising alternative to RT‐qPCR for point‐of‐care detection of PDCoV.


title: Role of CD151, A tetraspanin, in porcine reproductive and respiratory syndrome virus infection

text: BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA virus causing respiratory and reproductive diseases in swine. The susceptibility for PRRSV varies between the different breeds of swine. In cell culture, PRRSV virus can be propagated in primary porcine alveolar macrophages and some African green monkey kidney cell lines, such as MARC-145 cells. Previous studies have shown that 3' untranslated region (UTR) RNAs of the arteriviruses play an important role in the replication of the virus through interactions with cellular proteins. To better understand the differences in the replication capability of PRRSV in different cell lines, we sought to identify the host cellular proteins interacting with PRRSV 3' UTR RNA. We constructed a cDNA library of MARC-145 cell line in lambda ZAP Express vector and screened the library with the positive sense 3' UTR RNA of PRRSV. RESULTS: We found that CD151, a host cellular protein, interacting with PRRSV 3' UTR RNA. The specificity of the interaction between CD151 and PRRSV 3' UTR RNA was examined by gel shift assay as well as North-Western hybridization. The transfection of CD151 expression clone into BHK-21 rendered these cells susceptible to PRRSV infection, and the transfection of siRNA against CD151 into MARC-145 significantly reduced the level of PRRSV infection. Also, anti-CD151 antibody treatment to MARC-145 completely blocked PRRSV infection. CONCLUSION: Based on our results, we suggest that CD151 should cooperate in PRRSV infection in vitro in MARC-145 and BHK-21 cells.


title: Follow-up of the health conditions of an urban colony of free-roaming cats (Felis catus Linnaeus, 1758) in the city of Rio de Janeiro, Brazil

text: Abstract Similar to other urban areas where food and shelter are abundant, the zoological garden of Rio de Janeiro has dealt for years with a colony of feral or semi-feral domestic cats. A survey was conducted during 2002–2004 as a follow-up to a previous study in 2001 of the cat colony to identify pathogens circulating among the population and to annually follow the status of the cats to analyze morbidity coefficients and associations among infections and infestations identified in the colony. During the 3 years of the present study, 75 cats were sampled at least once, including 44 that were caught and examined only once, 14 that were examined twice, and 17 that were examined three times. For each cat that was caught, records were kept regarding sex, age, general health, and the presence of ectoparasites. Each year, a blood sample was taken for hematologic testing, platelet count, hemoparasite detection, antibodies to Toxoplasma gondii, and retrovirus detection. Blood counts were within normal range for the majority of cats tested. Feline immunodeficiency virus, fleas, and lice were detected in all years; however, incidence rates for each of these varied significantly throughout the years. Prevalence of Cytauxzoon spp., Mycoplasma spp., T. gondii infections were variable among the 3 years, although differences were not significant. Prevalence of feline leukemia virus increased significantly over the 3 years. Mycoplasma spp. and flea infestations were significantly associated, but no other associations among the pathogens were detected. Over the 3 years, the rate of new cat introductions decreased, and the pathogens showed a tendency to disseminate throughout the colony; however, there was virtually no evidence of clinically detectable disease. Therefore, it seems that stabilizing the population by a judicious control program facilitated the distribution of the pathogens throughout the colony, while the general well-being of the cats was not seriously affected.


title: Perspectives from Italy during the COVID-19 pandemic: nationwide survey-based focus on minimally invasive HPB surgery

text: The safety of minimally invasive procedures during COVID pandemic remains hotly debated, especially in a country, like Italy, where minimally invasive techniques have progressively and pervasively entered clinical practice, in both the hepatobiliary and pancreatic community. A nationwide snapshot of the management of HPB minimally invasive surgery activity during COVID-19 pandemic is provided: a survey was developed and conducted within AICEP (Italian Association of HepatoBilioPancreatic Surgeons) with the final aim of conveying the experience, knowledge, and opinions into a unitary report enabling more efficient crisis management. Results from the survey (81 respondents) show that, in Italian hospitals, minimally invasive surgery maintains its role despite the COVID-19 pandemic, with the registered reduction of cases being proportional to the overall reduction of the HPB surgical activity. Respondents agree that the switch from minimally invasive to open technique can be considered as a valid option for cases with a high technical complexity. Several issues merit specific attention: screening for virus positivity should be universally performed; only expert surgical teams should operate on positive patients and specific technical measures to lower the biological risk of contamination during surgery must be followed. Future studies specifically designed to establish the true risks in minimally invasive surgery are suggested. Furthermore, a standard and univocal process of prioritization of patients from Regional Healthcare Systems is advisable. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13304-020-00815-5) contains supplementary material, which is available to authorized users.


title: Development of a Rapid Automated Influenza A, Influenza B, and Respiratory Syncytial Virus A/B Multiplex Real-Time RT-PCR Assay and Its Use during the 2009 H1N1 Swine-Origin Influenza Virus Epidemic in Milwaukee, Wisconsin

text: Rapid, semiautomated, and fully automated multiplex real-time RT-PCR assays were developed and validated for the detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV) from nasopharyngeal specimens. The assays can detect human H1N1, H3N2, and swine-origin (S-OIV) H1N1 Flu A viruses and were effectively used to distinguish Flu A infections (of all subtypes) from Flu B and RSV infections during the current S-OIV outbreak in Milwaukee, WI. The analytical limits of detection were 10(−2) to 10(1) TCID(50)/ml depending on the platform and analyte and showed only one minor cross-reaction among 23 common respiratory pathogens (intermittent cross-reaction to adenovirus at >10(7) TCID(50)/ml). A total of 100 clinical samples were tested by tissue culture, both automated assays, and the US Food and Drug Administration-approved ProFlu+ assay. Both the semiautomated and fully automated assays exhibited greater overall (Flu A, Flu B, and RSV combined) clinical sensitivities (93 and 96%, respectively) and individual Flu A sensitivities (100%) than the Food and Drug Administration-approved test (89% overall sensitivity and 93% Flu A sensitivity). All assays were 99% specific. During the S-OIV outbreak in Milwaukee, WI, the fully automated assay was used to test 1232 samples in 2 weeks. Flu A was detected in 134 clinical samples (126 H1N1 S-OIV, 5 H1N1 [human], and 1 untyped) with 100% positive agreement compared with other “in-house” validated molecular assays, with only 2 false-positive results. Such accurate testing using automated high-throughput molecule systems should allow clinicians and public health officials to react quickly and effectively during viral outbreaks.


COVID-19 and the Air We Breathe


title: Various computed tomography findings of 2009 H1N1 influenza in 17 patients with relatively mild illness

text: PURPOSE: We retrospectively analyzed the computed tomography (CT) findings of H1N1 virus infection in 17 patients with relatively mild illness. MATERIALS AND METHODS: From September 2009 to January 2010, a total of 17 patients with confirmed H1N1 infection were included in the study (mean age 30.7 years). All patients were managed as outpatients or required short hospitalization without ventilation assistance. The CT scans were assessed for the presence of nodules, ground glass opacity (GGO), consolidation, bronchial wall thickening, reticulation, effusion, and lymph node enlargement. Location and distribution were evaluated. RESULTS: The most frequent manifestation was a mixture of nodules, consolidation, and GGO (5/17, 29.4%). In one case there was a focal area of bronchiolitis (centrilobular nodules with tree-in-bud appearance), and 10 of 17 cases (58.8%) showed bronchial wall thickening (findings of bronchitis/peribronchitis) and/or other abnormalities. In 16 of the 17 cases (94.1%) there were CT abnormalities with bilateral and random distribution without zonal predominance. Pleural effusions were seen in eight cases (47.1%). CONCLUSION: In contrast to several reports so far, CT findings of H1N1 virus infection in patients with mild illness are variable, including suggestive findings of inflammation involving large and/or small airways. This study showed various CT findings overlapping with other viral, atypical, or bacterial pneumonia and even cryptogenic organizing pneumonia.


title: ‘Healthcare Heroes’: problems with media focus on heroism from healthcare workers during the COVID-19 pandemic

text: During the COVID-19 pandemic, the media have repeatedly praised healthcare workers for their ‘heroic’ work. Although this gratitude is undoubtedly appreciated by many, we must be cautious about overuse of the term ‘hero’ in such discussions. The challenges currently faced by healthcare workers are substantially greater than those encountered in their normal work, and it is understandable that the language of heroism has been evoked to praise them for their actions. Yet such language can have potentially negative consequences. Here, I examine what heroism is and why it is being applied to the healthcare workers currently, before outlining some of the problems associated with the heroism narrative currently being employed by the media. Healthcare workers have a clear and limited duty to treat during the COVID-19 pandemic, which can be grounded in a broad social contract and is strongly associated with certain reciprocal duties that society has towards healthcare workers. I argue that the heroism narrative can be damaging, as it stifles meaningful discussion about what the limits of this duty to treat are. It fails to acknowledge the importance of reciprocity, and through its implication that all healthcare workers have to be heroic, it can have negative psychological effects on workers themselves. I conclude that rather than invoking the language of heroism to praise healthcare workers, we should examine, as a society, what duties healthcare workers have to work in this pandemic, and how we can support them in fulfilling these.


title: Silencing Viral Infection

text: The authors describe recent progress and obstacles to harnessing RNA interference to prevent or treat viral infection.


title: Inhibition of SARS-CoV-2 main protease 3CL(pro) by means of α-ketoamide and pyridone-containing pharmaceuticals using in silico molecular docking

text: The coronavirus disease infections (COVID-19) caused by a new type of coronavirus (SARS-CoV-2) have been emerging in the entire world. Therefore, it is necessary to find out potential therapeutic pharmaceuticals for this disease. This study investigates the inhibitory effect of the 3-chymotrypsin-like protease of SARS-CoV-2 (3CL(pro)) using pharmaceuticals containing α-ketoamide group and pyridone ring based on molecular docking. Of these, eight pharmaceuticals approved by US-Food and Drug Administration have shown good contact with the catalytic residues of 3CL(pro). They are telaprevir, temsirolimus, pimecrolimus, aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide. Their binding affinity score ranged from -5.6 to -7.4 kcal/mol. Hydrogen bonds were observed and reported. To the knowledge, this study report for the first time a compound that could be binding to ALA(285), the new residue resulting from genetic modification of 3CL(pro) of SARS-CoV-2 that has increased its catalytic activity 3.6-fold compared with its predecessor 3CL(pro) of SARS-CoV. It is recommended that telaprevir, and pyridone-containing pharmaceuticals including aminoglutethimide, apixaban, buspirone, lenalidomide, and pomalidomide be repurposed for COVID-19 treatment after suitable validation and clinical trials.


docid: tkhupnko

title: Care of the Pregnant Woman with COVID-19 in Labor and Delivery: Anesthesia, Emergency cesarean delivery, Differential diagnosis in the acutely ill parturient, Care of the newborn, and Protection of the healthcare personnel

text: COVID-19 in pregnancy can cause severe maternal morbidity in up to 9% of affected gravidae. Chest imaging is helpful in pregnant women who have a high pretest probability of COVID-19, but are RT-PCR negative. Vertical transmission is unlikely, but active measures are needed to prevent neonatal infection. We present an algorithm of care for the acutely ill parturient. We present a protocol for intrapartum care of the pregnant woman in labor.


Vaccination schedule for infants and COVID-19


title: Morbidity and Mortality Associated With Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplant: Too Little Defense or Harmful Immunity?

text: The impact on morbidity and mortality of Community Acquired Respiratory Virus (CARV) infections in patients undergoing Allogeneic Hematopoietic Cell Transplant (HCT) is widely studied. Here we give an overview of the current literature on the incidence and chance of progression to severe disease in this highly immune compromised population. We discuss the issue whether it is predominantly direct viral damage that causes clinical deterioration, or that it is in fact the allogeneic immuneresponse to the virus that is most important. This is an important question as it will guide therapeutic decision making. It asks for further collaborative studies focusing on sensitive surveillance with PCR techniques and relating clinical data with parameters of immune reconstitution.


title: Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits

text: Abstract Steroid-associated osteonecrosis (SAON) may lead to joint collapse and subsequent joint replacement. Poly lactic-co-glycolic acid/tricalcium phosphate (P/T) scaffold providing sustained release of icaritin (a metabolite of Epimedium-derived flavonoids) was investigated as a bone defect filler after surgical core-decompression (CD) to prevent femoral head collapse in a bipedal SAON animal model using emu (a large flightless bird). The underlying mechanism on SAON was evaluated using a well-established quadrupedal rabbit model. Fifteen emus were established with SAON, and CD was performed along the femoral neck for the efficacy study. In this CD bone defect, a P/T scaffold with icaritin (P/T/I group) or without icaritin (P/T group) was implanted while no scaffold implantation was used as a control. For the mechanistic study in rabbits, the effects of icaritin and composite scaffolds on bone mesenchymal stem cells (BMSCs) recruitment, osteogenesis, and anti-adipogenesis were evaluated. Our efficacy study showed that P/T/I group had the significantly lowest incidence of femoral head collapse, better preserved cartilage and mechanical properties supported by more new bone formation within the bone tunnel. For the mechanistic study, our in vitro tests suggested that icaritin enhanced the expression of osteogenesis related genes COL1α, osteocalcin, RUNX2, and BMP-2 while inhibited adipogenesis related genes C/EBP-ß, PPAR-γ, and aP2 of rabbit BMSCs. Both P/T and P/T/I scaffolds were demonstrated to recruit BMSCs both in vitro and in vivo but a higher expression of migration related gene VCAM1 was only found in P/T/I group in vitro. In conclusion, both efficacy and mechanistic studies show the potential of a bioactive composite porous P/T scaffold incorporating icaritin to enhance bone defect repair after surgical CD and prevent femoral head collapse in a bipedal SAON emu model.


title: Survey of acute hospital infection control resources and services in the Republic of Ireland

text: Summary Following the development of national guidelines on the control of antimicrobial resistance in 2001, a survey was carried out in 2003 of all 68 acute hospitals in the Republic of Ireland on resources available and current practice to control and prevent nosocomial infection. Completed questionnaires were received from 66 hospitals (97%). The median number of acute inpatient beds per hospital was 156; this was 522 in regional/tertiary referral centres. Only 31 (47%) hospitals had on-site consultant microbiologist sessions, and there was an infection control nurse in 56 (85%) hospitals. Eighteen (29%) hospitals had an occupational health physician, and 48 (73%) hospitals had an infection control committee. There was a median of one isolation room for every 16 acute beds, and a median of five rooms with en-suite bathroom facilities per hospital in those hospitals that provided data. All hospitals had documented infection control policies, and these were available in electronic format in 25 (38%) hospitals. Fifty-five (83%) hospitals undertook surveillance of nosocomial infection, and alcohol-based hand hygiene facilities were available, either at a handwashing sink or at the entrance to a ward, in 57 (86%) hospitals. In the Republic of Ireland, there remains a significant shortage of microbiologists/infection control doctors, occupational health physicians and infection control nurses. Isolation facilities are also inadequate. Although there is much agreement internationally on the importance of nosocomial infection and the priorities for surveillance, there are no agreed basic minimum standards for the resources and facilities necessary to control and prevent nosocomial infection.


title: Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort

text: BACKGROUND: Information about incidence, clinical characteristics, and outcomes of HIV-infected individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is scarce. We characterised individuals with COVID-19 among a cohort of HIV-infected adults in Madrid. METHODS: In this observational prospective study, we included all consecutive HIV-infected individuals (aged ≥18 years) who had suspected or confirmed COVID-19 as of April 30, 2020, at the Hospital Universitario Ramón y Cajal (Madrid, Spain). We compared the characteristics of HIV-infected individuals with COVID-19 with a sample of HIV-infected individuals assessed before the COVID-19 pandemic, and described the outcomes of individuals with COVID-19. FINDINGS: 51 HIV-infected individuals were diagnosed with COVID-19 (incidence 1·8%, 95% CI 1·3–2·3). Mean age of patients was 53·3 years (SD 9·5); eight (16%) were women, and 43 (84%) men. 35 (69%) cases of co-infection had laboratory confirmed COVID-19, and 28 (55%) required hospital admission. Age and CD4 cell counts in 51 patients diagnosed with COVID-19 were similar to those in 1288 HIV-infected individuals without; however, 32 (63%) with COVID-19 had at least one comorbidity (mostly hypertension and diabetes) compared with 495 (38%) without COVID-19 (p=0·00059). 37 (73%) patients had received tenofovir before COVID-19 diagnosis compared with 487 (38%) of those without COVID-19 (p=0·0036); 11 (22%) in the COVID-19 group had previous protease inhibitor use (mostly darunavir) compared with 175 (14%; p=0·578). Clinical, analytical, and radiological presentation of COVID-19 in HIV-infected individuals was similar to that described in the general population. Six (12%) individuals were critically ill, two of whom had CD4 counts of less than 200 cells per μL, and two (4%) died. SARS-CoV-2 RT-PCR remained positive after a median of 40 days from symptoms onset in six (32%) individuals, four of whom had severe disease or low nadir CD4 cell counts. INTERPRETATION: HIV-infected individuals should not be considered to be protected from SARS-CoV-2 infection or to have lower risk of severe disease. Generally, they should receive the same treatment approach applied to the general population. FUNDING: None.


title: Determinants of translational fidelity and efficiency in vertebrate mRNAs

text: Abstract This article reviews current knowledge on the mechanisms affecting the fidelity of initiation codon selection, and discusses the effects of structural features in the 5′-non-coding region on the efficiency of translation of messenger RNA molecules.


title: Modelling the spreading rate of controlled communicable epidemics through an entropy-based thermodynamic model

text: A model based on a thermodynamic approach is proposed for predicting the dynamics of communicable epidemics in a city, when the epidemic is governed by controlling efforts of multiple scales so that an entropy is associated with the system. All the epidemic details are factored into a single parameter that is determined by maximizing the rate of entropy production. Despite the simplicity of the final model, it predicts the number of hospitalized cases with a reasonable accuracy, using the data of SARS of the year 2003, once the inflexion point characterizing the effect of multiple controlling efforts is known. This model is supposed to be of potential usefulness since epidemics such as avian influenza like H7H9 in China this year have the risk to become communicable among human beings.


title: Chapter 39 Viral Syndromes

text: Abstract The chapters in this textbook deal with those viruses causing human disease, and the various modes of replication, transmission, and disease-causing processes that contribute to a particular clinical presentation. This final chapter focuses on each of the major clinical syndromes and outlines the contribution of particular viruses to each one, thereby serving as a pointer to elsewhere among earlier chapters where more specific information can be found. These virus–disease associations have been presented in tabular form for ease of reference.


title: Genome-wide expression profiling shows transcriptional reprogramming in Fusarium graminearum by Fusarium graminearum virus 1-DK21 infection

text: BACKGROUND: Fusarium graminearum virus 1 strain-DK21 (FgV1-DK21) is a mycovirus that confers hypovirulence to F. graminearum, which is the primary phytopathogenic fungus that causes Fusarium head blight (FHB) disease in many cereals. Understanding the interaction between mycoviruses and plant pathogenic fungi is necessary for preventing damage caused by F. graminearum. Therefore, we investigated important cellular regulatory processes in a host containing FgV1-DK21 as compared to an uninfected parent using a transcriptional approach. RESULTS: Using a 3′-tiling microarray covering all known F. graminearum genes, we carried out genome-wide expression analyses of F. graminearum at two different time points. At the early point of growth of an infected strain as compared to an uninfected strain, genes associated with protein synthesis, including ribosome assembly, nucleolus, and ribosomal RNA processing, were significantly up-regulated. In addition, genes required for transcription and signal transduction, including fungal-specific transcription factors and cAMP signaling, respectively, were actively up-regulated. In contrast, genes involved in various metabolic pathways, particularly in producing carboxylic acids, aromatic amino acids, nitrogen compounds, and polyamines, showed dramatic down-regulation at the early time point. Moreover, genes associated with transport systems localizing to transmembranes were down-regulated at both time points. CONCLUSION: This is the first report of global change in the prominent cellular pathways in the Fusarium host containing FgV1-DK21. The significant increase in transcripts for transcription and translation machinery in fungal host cells seems to be related to virus replication. In addition, significant down-regulation of genes required for metabolism and transporting systems in a fungal host containing the virus appears to be related to the host defense mechanism and fungal virulence. Taken together, our data aid in the understanding of how FgV1-DK21 regulates the transcriptional reprogramming of F. graminearum.


The explosion in scabies cases during COVID‐19 pandemic


title: Pulmonary delivery of nanostructured lipid carriers for effective repurposing of salinomycin as an antiviral agent

text: Coronavirus disease outbreak caused a severe public health burden all over the world. Salinomycin (SAL) is a broad-spectrum antibiotic that had drawn attention in selective targeting of cancer and viral infections. Recent drug screen identified SAL as a potent antiviral agent against SARS-CoV-2. In this review we discuss the potential of pulmonary delivery of SAL using nanostructured lipid carriers (NLCs) against SARS-CoV-2.


Predicting severe outcomes in COVID-19


title: Japanese encephalitis virus: A multi-epitope loaded peptide vaccine formulation using reverse vaccinology approach

text: Abstract Japanese encephalitis (JE) is a serious leading health complication emerging expansively that has severely affected the survival rate of human beings. This fatal disease is caused by JE Virus (JEV). The current study was carried out for designing a multi-epitope loaded peptide vaccine to prevent JEV. Based on reverse vaccinology and in silico approaches, octapeptide B-cell and hexapeptide T-cell epitopes belonging to five proteins, viz. E, prM, NS1, NS3 and NS5 of JEV were determined. Hydrophilicity, antigenicity, immunogenicity and aliphatic amino acids of the epitopes were estimated. Further, the epitopes were analyzed for different physicochemical parameters, e.g. total net charges, amino acid composition and Boman index. Out of all the epitopes, a total of four T-cell epitopes namely KRADSS, KRSRRS, SKRSRR and KECPDE and one B-cell epitope i.e. PKPCSKGD were found to have potential for raising immunity in human against the pathogen. Taking into account the outcome of this study, the pharmaceutical industries could initiate efforts to combine the identified epitopes together with adjuvant or carrier protein to develop a multi-epitope-loaded peptide vaccine against JEV. The peptide vaccine, being cost effective, could be administered as a prophylactic measure and in JEV infected individuals to combat the spread of this virus in human population. However, prior to administration into human beings, the vaccine must pass through several clinical trials.


title: Surveillance and Preparedness for Ebola Virus Disease — New York City, 2014

text: In July 2014, as the Ebola virus disease (Ebola) epidemic expanded in Guinea, Liberia, and Sierra Leone, an air traveler brought Ebola to Nigeria and two American health care workers in West Africa were diagnosed with Ebola and later medically evacuated to a U.S. hospital. New York City (NYC) is a frequent port of entry for travelers from West Africa, a home to communities of West African immigrants who travel back to their home countries, and a home to health care workers who travel to West Africa to treat Ebola patients. Ongoing transmission of Ebolavirus in West Africa could result in an infected person arriving in NYC. The announcement on September 30 of an Ebola case diagnosed in Texas in a person who had recently arrived from an Ebola-affected country further reinforced the need in NYC for local preparedness for Ebola.


title: Regional localization of virus in the central nervous system of mice persistently infected with murine coronavirus JHM

text: Abstract Suckling C57BU6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop either a fatal acute encephalomyelitis or a late onset demyelinating disease, depending on whether they are nursed by unimmunized or immunized dams. To determine the localization of virus-specific RNA, serial sections of brains from infected and uninfected mice were annealed with a 35S-labeled antisense RNA probe and analyzed by film autoradiography. In the mice with acute encephalomyelitis, viral RNA was present in the mesencephalon, hypothalamus, hippocampus, basal ganglia, subcortical white matter, and thalamus. Viral RNA was detected in the spinal cords of all mice with the late onset, demyelinating encephalomyelitis, but was distributed into three different patterns in the brains of these mice, even though all had the same clinical disease. In the first group, viral RNA was detected only in the brainstem. In the second group, viral RNA was detected in the brainstem, thalamus, and cerebral grey matter. This distribution was consistent with viral spread along well-defined tracts connecting these parts of the brain. In the third group, viral RNA could be detected both in the brainstem and in several white matter tracts within close physical proximity to the optic chiasm. This distribution was consistent with viral spread by an extracellular route from one white matter tract to other tracts which were physically close, but which were not part of the same pathways. These results suggest that MHV-JHM spreads through the central nervous system both along well-defined neuronal pathways and by spread from contiguous structures, but also suggest that viral replicates preferentially in a limited number of areas of the brain. The technique of in situ hybridization with film autoradiography should be generally useful for analyzing macroscopic movements of virus within infected organs.


docid: txdlgghh

title: 8 Electrospinning and microfluidics An integrated approach for tissue engineering and cancer

text: Abstract Progress in microfluidic technology has enabled precise manipulation of small volumes of fluids, leading to the development of low-cost and portable systems that have shown considerable promise in biomedicine. Although these functional devices have gained a great deal of attention over the past decades, a new fascinating trend concerns the integration of microfluidics with other fabrication techniques, with particular regard to electrospinning and additive manufacturing.In this chapter, the attention will be focused on integrative approaches obtained combining microfluidics and electrospinning, highlighting the recent advances and challenges in the tissue-engineering framework. Indeed, although this innovative trend is still at its beginning, significant results have been achieved both in the microfluidic-aided fabrication of novel microstructured materials and in the development of new biosensors and analytical devices for point-of-care diagnostics.


“The Art of War” in the Era of Coronavirus Disease 2019 (COVID-19)


title: Long-term safety and efficacy of a pasteurized nanofiltrated prothrombin complex concentrate (Beriplex P/N): a pharmacovigilance study

text: BACKGROUND: The rapid reversal of the effects of vitamin K antagonists is often required in cases of emergency surgery and life-threatening bleeding, or during bleeding associated with high morbidity and mortality such as intracranial haemorrhage. Increasingly, four-factor prothrombin complex concentrates (PCCs) containing high and well-balanced concentrations of vitamin K-dependent coagulation factors are recommended for emergency oral anticoagulation reversal. Both the safety and efficacy of such products are currently in focus, and their administration is now expanding into the critical care setting for the treatment of life-threatening bleeding and coagulopathy resulting either perioperatively or in cases of acute trauma. METHODS: After 15 yr of clinical use, findings of a pharmacovigilance report (February 1996–March 2012) relating to the four-factor PCC Beriplex P/N (CSL Behring, Marburg, Germany) were analysed and are presented here. Furthermore, a review of the literature with regard to the efficacy and safety of four-factor PCCs was performed. RESULTS: Since receiving marketing authorization (February 21, 1996), ∼647 250 standard applications of Beriplex P/N have taken place. During this time, 21 thromboembolic events judged to be possibly related to Beriplex P/N administration have been reported, while no incidences of viral transmission or heparin-induced thrombocytopenia were documented. The low risk of thromboembolic events reported during the observation period (one in ∼31 000) is in line with the incidence observed with other four-factor PCCs. CONCLUSIONS: In general, four-factor PCCs have proven to be well tolerated and highly effective in the rapid reversal of vitamin K antagonists.


title: Discovery of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as new apoptosis inducers using a cell- and caspase-based HTS assay

text: We report the discovery of a series of substituted N′-(2-oxoindolin-3-ylidene)benzohydrazides as inducers of apoptosis using our proprietary cell- and caspase-based ASAP HTS assay. Through SAR studies, N′-(4-bromo-5-methyl-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (3g) was identified as a potent apoptosis inducer with an EC(50) value of 0.24 μM in human colorectal carcinoma HCT116 cells, more than a 40-fold increase in potency from the initial screening hit N′-(5-bromo-2-oxoindolin-3-ylidene)-3,4,5-trimethoxybenzohydrazide (2a). Compound 3g also was found to be highly active in a growth inhibition assay with a GI(50) value of 0.056 μM in HCT116 cells. A group of potentially more aqueous soluble analogs were prepared and found to be highly active. Among them, compound 4e incorporating a methyl piperazine moiety was found to have EC(50) values of 0.17, 0.088 and 0.14 μM in human colorectal carcinoma cells HCT116, hepatocellular carcinoma cancer SNU398 cells and human colon cancer RKO cells, respectively. Compounds 3g and 4e were found to function as inhibitors of tubulin polymerization.


title: Airflow and droplet spreading around oxygen masks: A simulation model for infection control research

text: BACKGROUND: Respiratory assist devices, such as oxygen masks, may enhance the potential to spread infectious aerosols from patients with respiratory infections. METHODS: A technique was developed to visualize exhaled aerosols during simulated patients' use of oxygen masks in a health care setting and tested using the simple, the nonrebreathing, and the Venturi oxygen masks. A smoke tracer was introduced into one of the lungs of the model to enable it to mix with the incoming oxygen and then to be further inhaled/exhaled by the model according to a variety of realistic respiratory settings (14, 24, and 30 breaths per minute, with tidal volumes of 500, 330, 235 mL, respectively) and oxygen supply flow rates (between 6 and 15 liters per minute). Digital recordings of these exhaled airflow patterns allowed approximate distances to be estimated for the extent of the visible exhaled air plumes emitted from each oxygen mask type at these settings. RESULTS: It was found that the simple, the nonrebreathing, and the Venturi-type oxygen masks produced exhaled smoke plumes over minimum distances of 0.08 to 0.21 m, 0.23 to 0.36 m, and 0.26 to 0.40 m, respectively. CONCLUSION: Health care workers may therefore consider any area within at least 0.4 m of a patient using such oxygen masks to be a potential nosocomial hazard zone.


docid: sneqefec

title: Coronaviruses: General Features

text: Coronaviruses have the largest known RNA genomes (∼30kb), which are of positive sense. Together with toroviruses, they are classified in the family Coronaviridae, order Nidovirales. All coronaviruses have four common proteins, three in the envelope and one associated with the genome. Assembly of virus particles occurs at internal membranes. The genes for the structural proteins are at the 3′ end of the genome. Most of the genome (∼20kb) is gene 1, which encodes 15–16 proteins associated with RNA replication and transcription. Translation of gene 1 involves ribosomal frameshifting. Transcription is by a discontinuous process which results in a 3′ co-terminal nested set of mRNAs, each of which has a common leader sequence transcribed from the 5′ terminus of the genome. Only the most 5′-proximal gene of each mRNA is translated. Recombination is a feature of coronavirus evolution. The outbreak of severe acute respiratory syndrome (SARS) has resulted in the discovery of more coronaviruses in humans, other mammals, and avian species, and the realization that the host range of coronaviruses is wider than previously acknowledged. Coronaviruses are associated with a wide range of diseases, including the respiratory and enteric systems, though not necessarily restricted to these, for example, some coronaviruses affect the central nervous system, kidneys, and gonads. The most widely used coronavirus vaccine (billions of doses annually) is against infectious bronchitis virus, which affects chickens.


title: Pathology of the thyroid in severe acute respiratory syndrome

text: Summary The severe acute respiratory syndrome (SARS) epidemic started in November 2002 and spread worldwide. The pathological changes in several human organs of patients with SARS have been extensively described. However, to date, little has been reported about the effects of this infection on the thyroid gland. Femoral head necrosis and low serum triiodothyronine and thyroxine levels, commonly found in patients with SARS, raise the possibility of thyroid dysfunction. We have undertaken this study to evaluate for any potential injury to the thyroid gland caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay was performed to identify apoptotic cells. The follicular epithelium was found to be damaged with large numbers of cells exfoliated into the follicle. The terminal deoxynucleotidyl transferase-mediated dUPT nick end–labeling assay demonstrated many cells undergoing apoptosis. Follicular architecture was altered and showed distortion, dilatation, and collapse. No distinct calcitonin-positive cells were detectable in the SARS thyroids. In conclusion, both parafollicular and follicular cells were injured. This may provide an explanation both for low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients with SARS. Apoptosis may play a role in the pathogenesis of SARS associated coronavirus infection in the thyroid gland.


title: Effects of environmental disinfection on the isolation of vancomycin-resistant Enterococcus after a hospital-associated outbreak of Middle East respiratory syndrome

text: Environmental disinfection with sodium hypochlorite and hydrogen peroxide vapor was performed after a hospital-associated outbreak of Middle East respiratory syndrome. Although only 11% of total beds were disinfected, the isolation and vancomycin-resistance rates of Enterococcus spp significantly decreased for 2 months, whereas other multidrug-resistant organisms did not.


title: Virogenomics: the virus–host interaction revisited

text: Genomics tools allow us to assess gene expression ‘genome wide’ providing an unprecedented view on the host-side of the virus–host interaction. The success of the application of these tools crucially depends on our ability to reduce the total information load while increasing the information density of the data collected. In addition to the advanced data analysis algorithms, gene annotation-pathway databases, and theoretical models, specifically designed sets of complementary experiments are crucial in translating the collected genomics data into palatable knowledge. A better understanding of the molecular basis of virus–host interactions will support the rational design of improved and novel intervention strategies for viral infections.


Heart Rhythm Society Expert Consensus Statement on Electrophysiology Laboratory Standards: Process, Protocols, Equipment, Personnel, and Safety


title: Enigmatic Histamine Receptor H(4) for Potential Treatment of Multiple Inflammatory, Autoimmune, and Related Diseases

text: The histamine H(4) receptor, belonging to the family of G-protein coupled receptors, is an increasingly attractive drug target. It plays an indispensable role in many cellular pathways, and numerous H(4)R ligands are being studied for the treatment of several inflammatory, allergic, and autoimmune disorders, including pulmonary fibrosis. Activation of H(4)R is involved in cytokine production and mediates mast cell activation and eosinophil chemotaxis. The importance of this receptor has also been shown in inflammatory models: peritonitis, respiratory tract inflammation, colitis, osteoarthritis, and rheumatoid arthritis. Recent studies suggest that H(4)R acts as a modulator in cancer, neuropathic pain, vestibular disorders, and type-2 diabetes, however, its role is still not fully understood.


title: Contributions of Farm Animals to Immunology

text: By their very nature, great advances in immunology are usually underpinned by experiments carried out in animal models and inbred lines of mice. Also, their corresponding knock-out or knock-in derivatives have been the most commonly used animal systems in immunological studies. With much credit to their usefulness, laboratory mice will never provide all the answers to fully understand immunological processes. Large animal models offer unique biological and experimental advantages that have been and continue to be of great value to the understanding of biological and immunological processes. From the identification of B cells to the realization that γδ T cells can function as professional antigen presenting cells, farm animals have contributed significantly to a better understanding of immunity.


title: Human bocavirus, coronavirus, and polyomavirus detected among patients hospitalised with severe acute respiratory illness in South Africa, 2012 to 2013

text: AIM: To investigate the prevalence of human bocavirus (hBoV), human coronaviruses (hCoV), and human polyomaviruses (hPyV) among patients with severe acute respiratory illness (SARI), in South Africa. METHODS: The study included 680 South African patients randomly selected in age‐defined categories from hospitalised patients enrolled through SARI surveillance during 2012 to 2013. A multiplex reverse transcription real‐time polymerase chain reaction assay was used to detect hBoV; hCoV‐OC43, hCoV‐229E, hCoV‐NL63, and hCoV‐HKU1; and Washington University hPyV (hPyV‐WU) and Karolinska Insitute hPyV (hPyV‐KI), in respiratory tract specimens collected from patients with SARI. All respiratory specimens from patients enrolled through SARI surveillance were also routinely tested by multiplex reverse transcription real‐time polymerase chain reaction for adenovirus; enterovirus; human metapneumovirus; parainfluenza virus types 1, 2, and 3; respiratory syncytial virus; rhinovirus; influenza A, and influenza B. RESULTS: Human bocavirus, hCoV‐229E, and hPyV‐WU were detected in 3.7% (25/680), 4.1% (28/680), and 4.1% (28/680) of respiratory specimens, respectively. All other viruses were detected in <2% of specimens. Rhinovirus was the most common coinfecting virus (21.4%‐60.7%), followed by adenovirus (21.4%‐39.3%), and respiratory syncytial virus (10.7%‐24.0%). Testing for the additional viruses (hBoV, hCoV, and hPyV) decreased the number of specimens that initially tested negative by 2.9% (20/680). CONCLUSION: Inclusion of laboratory tests for hBoV, hCoV‐229E, and hPyV‐WU in differential testing algorithms for surveillance and diagnostics for suspected cases of respiratory illness of unknown cause may improve our understanding of the etiology of SARI, especially in a country like South Africa with a high number of immune compromised persons.


Global Health Security Alliance (GloHSA)


docid: dquvysba

title: 4 Smart durable and self-healing textile coatings

text: Abstract The durability of textiles can be endangered in different ways. Various treatments are used to protect textiles against degradation or damage or even to restore or repair the initial properties. Other technologies are still under investigation. In this chapter an overview is presented of the work done in our laboratory in the area of smart coatings protecting textiles.


Nuevo coronavirus (2019-nCov): ¿tiene suficientes unidades de cuidados intensivos?


title: Feline gut microbiota composition in association with feline coronavirus infection: A pilot study

text: Abstract Feline coronaviruses (FCoV) colonize the intestinal tract, however, due to not fully understood mutations, they can spread systemically and cause feline infectious peritonitis (FIP). Recent studies on human medicine report that gut microbiota is involved in the development of systemic disorders and could influence the immune response to viral diseases. The aim of this study was to provide preliminary data on the fecal microbiota composition in healthy cats compared to FCoV-infected cats, with and without FIP. Cats were equally grouped as healthy FCoV-negative, healthy FCoV-positive or FIP affected (total n = 15). Fecal sample were evaluated for the microbiota composition. A total of 3,231,916 sequences were analyzed. The samples' alpha-diversity curves did not reach a proper plateau and, for the beta-diversity, the samples seemed not to group perfectly by category, even if the healthy FCoV-positive group showed a hybrid microbial composition between FCoV-negative and FIP groups. Although there were no taxa significantly linked to the different conditions, some peculiar patterns were recognized: Firmicutes was always the most represented phylum, followed by Bacteroidetes and Actinobacteria. In FCoV-positive cats, the Firmicutes and Bacteroidetes were respectively over- and under-represented, compared to the other groups. Among FIP cats, three subjects shared a similar microbiome, one cat showed a different microbial profile and the other one had the lowest number of diverse phyla. Despite the limited number of animals, some differences in the fecal microbiome between the groups were observed, suggesting to further investigate the possible correlation between gut microbiota and FCoV infection in cats.


title: A possible link between recurrent upper respiratory tract infections and lower cytokine production in patients with Q fever fatigue syndrome

text: Besides fatigue, many Q fever fatigue syndrome (QFS) patients also complain of frequently recurring upper respiratory tract infections with severe symptoms. We investigated whether immunologic dysregulation contributes to these complaints. Cytokine and chemokine production was measured after stimulating monocytes of QFS patients and age‐ and sex‐matched healthy controls with LPS and several viral ligands. The H3K4me3 mark of open chromatin was measured at the promoter regions of cytokines and chemokines that differed significantly from healthy controls. Monocytes of QFS patients produced significantly less TNF‐α (p = 0.032), IL‐1β (0.004, 0.024, and 0.008), IL‐6 (0.043), RANTES (0.033), IP‐10 (0.049), MCP‐1 (0.022), IL‐ 13 (0.029), and IL‐10 (0.026) than healthy controls when stimulated with various ligands. H3K4me3 expression was significantly lower in QFS patients than in healthy controls on the promoter regions of IL‐1β (p = 0.004), MCP‐1 (<0.001 and <0.001), IP‐10 (<0.001), IL‐10 (0.041), and IL‐13 (<0.001, <0.001, and 0.001). QFS patients showed diminished cytokine responses to various stimuli compared to age‐ and sex‐matched healthy controls, likely due to epigenetic remodeling and long‐term memory as a result from the acute Q fever infection. This might explain the upper respiratory tract ailments in QFS.


title: Antivirales (a excepción del VIH y la hepatitis)

text: Los antivirales son en la actualidad un sector esencial de la farmacopea antiinfecciosa. Incluso si no se tienen en cuenta los antirretrovirales y los antivirales dirigidos contra los virus de la hepatitis B y C, que constituyen una parte muy importante, existen varias moléculas que se utilizan en la práctica clínica que permiten luchar eficazmente contra las infecciones por virus herpes, adenovirus, poxvirus, virus del papiloma y virus de la gripe. La mayoría de estas moléculas se dirigen contra las enzimas virales implicadas en la replicación de los genomas virales. La mayoría de los análogos nucleosídicos (de los que el arquetipo es el aciclovir) y los análogos nucleotídicos (cuyo arquetipo es el cidofovir) requieren una fosforilación previa para inhibir, por un mecanismo de competición y, en ocasiones de terminación, la actividad de una polimerasa de ADN (ácido desoxirribonucleico). El foscarnet, análogo de pirofosfato, ejerce esta inhibición directamente sin modificación. En la actualidad, se dispone de menos antivirales para los virus ARN (ácido ribonucleico) que para los de ADN, aunque los inhibidores de la neuraminidasa han demostrado su eficacia contra los virus de la gripe. La especificidad de los antivirales suele ser estrecha, limitada por lo general para cada molécula a unos pocos virus relacionados. Las otras limitaciones del uso actual de los antivirales son la imposibilidad de erradicar las infecciones virales latentes, la aparición de resistencia, los efectos indeseables relacionados en gran parte con la toxicidad celular relativa de las moléculas y su coste. Se esperan avances tanto en la eficacia de los antivirales como en su tolerabilidad clínica y el número de las enfermedades virales tratadas. Es esencial que las exigencias económicas no restrinjan la dinámica de uno de los ámbitos más innovadores de la medicina contemporánea.


title: Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine in a blinded, randomized, placebo-controlled trial of adults in Mexico

text: Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18–64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 μg, 15 μg, or 45 μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 μg VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 μg and 45 μg) compared to the placebo and 5 μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82–92% of all subjects and in 64–85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.


The Association of Voter Turnout with County-level COVID-19 Occurrence Early in the Pandemic


title: Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity

text: Abstract Objective With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)–based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. Study design Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. Methods The evaluated rapid test is an IgG/IgM–based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. Results Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). Conclusion Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.


title: Detection and molecular characterization of caliciviruses (vesivirus and norovirus) in an outbreak of acute diarrhea in kittens from Brazil

text: Abstract Feline caliciviruses (FCVs) have occasionally been described in cats in association with enteric disease, but an etiological role for these viruses in acute gastroenteritis is still unclear. In this study, molecular characterization of FCV and feline norovirus (FNoV) was undertaken using real-time PCR (RT-PCR) and sequence analysis of the ORF1 region in fecal specimens from 29 diarrheic cats. The specimens were also screened for parvovirus, coronavirus, astrovirus and group A rotavirus. A quantitative one step RT-PCR was also performed to detect and quantitate NoV genogroup IV and the role of these animal caliciviruses in feline gastroenteritis was investigated. This is the first description of enteric FCV and FNoV in South America.


title: The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression

text: Many viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins required for viral replication are still synthesized during shutoff. The molecular determinants of target selectivity in host shutoff remain incompletely understood. Here, we report that the influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with cellular proteins involved in RNA splicing. The interaction with splicing contributes to target discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds light on the specificity of viral control of host gene expression and may provide opportunities for development of new host-targeted antivirals.


title: Quantifying the bat bushmeat trade in North Sulawesi, Indonesia, with suggestions for conservation action

text: Abstract The intense consumption of flying foxes in North Sulawesi, Indonesia has raised hunting pressure and extirpation is expected to spread into other regions. To assess local cultural attitudes towards bats for formulating a targeted conservation campaign, we conducted a survey of consumption practices of bats in 2013 at the eight major markets near Manado. Locals eat flying foxes at least once a month, but the frequency increases tenfold around Christian holidays. Approximately 500 metric tons of bats are imported from other provinces, with South Sulawesi as the main provider at 38%. No action has been taken to conserve the bats, as continued abundance in the market masks the effects of the bushmeat trade on wild populations. We suggest: (1) engaging churches as conduits for environmental education and quota enforcement; (2) legal regulation of interprovincial trade; (3) substituting bats with a sustainable option; (4) involving local students as campaigners to ensure higher receptiveness from local communities. Grassroots conservation initiatives combined with enforcement of existing laws aim to affect change on a local level, which has been successful in other conservation programs. These efforts would not only progress bat conservation, but conservation of other rare, endemic mammals common to the bushmeat trade.


title: WFDC1/ps20: A host factor that influences the neutrophil response to murine hepatitis virus (MHV) 1 infection

text: Abstract The whey acidic protein family member, WFDC1/ps20 is a permissivity factor in HIV infection. Herein we describe a contrasting role for ps20 in limiting MHV-1 infection. Intranasal MHV-1 infection produces a respiratory infection in mice. Using ps20 knockout mice we provide evidence that intranasal MHV-1 infection results in increased lung viral titers in ps20−/− compared to ps20+/+ mice. Accompanying MHV-1 infection we observe an increase in the number of neutrophils infiltrating the BAL and an increase in the percentage of neutrophils in the lung draining lymph nodes of ps20−/− compared with ps20+/+ mice. Gene expression levels for the neutrophil chemoattractants CXCL1 and CXCL2 are elevated in the lungs of ps20−/− mice post-MHV-1 infection. Characterization of the immune cell profile in naïve ps20−/− mice revealed an increase in circulating neutrophils compared to ps20+/+ mice. No notable differences in other immune cell profiles were observed between the ps20+/+ and ps20−/− mice. Accordingly, we examined MHV-1 infection of neutrophils and provide evidence that neutrophils isolated from ps20−/− mice are more susceptible to MHV-1 infection than neutrophils isolated from ps20+/+ mice. These data suggest roles for ps20 in regulating expression of neutrophil-specific chemotactic factors, thereby potentially modulating neutrophil migration, and in modulating neutrophil susceptibility to MHV-1 infection.


title: 33rd international mammalian genome conference: meeting highlights

text: Scientists from 12 countries met at the International Mammalian Genome Conference (IMGC) to share advances in mammalian genetics and genomics research. The event was held in Strasbourg, France and represents the city’s second time hosting the IMGC. A diverse attendance of pre-doctoral and post-doctoral trainees, young investigators, established researchers, clinicians, bioinformaticians, and computational biologists enjoyed a rich scientific program of 63 oral presentations, 65 posters, and 5 workshops in the fields of epigenetics, system genetics, developmental biology, cancer, human disease modeling, technical advances, and bioinformatics. This report presents selected highlights of this meeting which illustrate how recent advances in mammalian genetic approaches have improved our ability to decipher complex biological mechanisms.


title: A review of vaccine development and research for industry animals in Korea

text: Vaccination has proven to be the most cost-effective strategy for controlling a wide variety of infectious diseases in humans and animals. For the last decade, veterinary vaccines have been substantially developed and demonstrated their effectiveness against many diseases. Nevertheless, new vaccines are greatly demanded to effectively control newly- and re-emerging pathogens in livestock. However, development of veterinary vaccines is a challenging task, in part, due to a variety of pathogens, hosts, and the uniqueness of host-susceptibility to each pathogen. Therefore, novel concepts of vaccines should be explored to overcome the limitation of conventional vaccines. There have been greatly advanced in the completion of genomic sequencing of pathogens, the application of comparative genomic and transcriptome analysis. This would facilitate to open opportunities up to investigate a new generation of vaccines; recombinant subunit vaccine, virus-like particle, DNA vaccine, and vector-vehicle vaccine. Currently, such types of vaccines are being actively explored against various livestock diseases, affording numerous advantages over conventional vaccines, including ease of production, immunogenicity, safety, and multivalency in a single shot. In this articles, the authors present the current status of the development of veterinary vaccines at large as well as research activities conducted in Korea.


title: CXC chemokines and antimicrobial peptides in rhinovirus‐induced experimental asthma exacerbations

text: RATIONALE: Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV‐induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophil‐related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV‐induced exacerbations of asthma. METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LL‐37) and neutrophil chemokines (CXCL1/GRO‐α, CXCL2/GRO‐β, CXCL5/ENA‐78, CXCL6/GCP‐2, CXCL7/NAP‐2, and CXCL8/IL‐8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post‐experimental infection. RESULTS: BAL HNP 1–3 and Elafin were higher, CXCL7/NAP‐2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1–3 and CXCL8/IL‐8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1–3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1–3 or IL‐8 levels. CONCLUSIONS: We propose that RV infection in asthma leads to increased release of CXCL8/IL‐8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL‐8 may be useful in treatment of virus‐induced asthma exacerbations.


Breast milk and infection


title: Effects of specialty proteins as alternatives to bovine or porcine spray-dried plasma in non-medicated diets fed to weaned pigs housed in an unsanitary environment

text: Two experiments were done to compare growth performance of pigs weaned at 21 ± 2 d of age that were housed in unsanitary pens and fed non-medicated diets containing alternative proteins versus spray-dried porcine (SDPP; Exp. 1) or bovine (SDBP; Exp. 2) plasma. Experiment 1 used 360 pigs fed 1 of 6 experimental diets from d 0 to 15, followed by a common diet fed to all pigs from d 15 to 28 post-weaning with 11 pens of 5 or 6 pigs/pen allotted per treatment. Experimental diets were based on 8.04% soy protein concentrate (SPC) as the control protein or a similar diet with either 2.50 or 5.00% SDPP or 0.17, 0.33, or 1.00% activated porcine plasma (APP) replacing SPC on an equal Lys basis. Experiment 2 used 300 pigs that were fed 1 of 6 experimental diets from d 0 to 14 post-weaning with 10 pens of 4 to 6 pigs/pen allotted per diet. Experiment 2 diets were based on 8.04% SPC as the control protein source or similar diets with the following specialty proteins replacing SPC on an equal Lys basis: 0.40% APP; 10.66% enzymatically hydrolyzed soy and yeast protein (EHSY); a combination (CB) of 6.36% EHSY, 0.40% APP, and 2.50% fish meal; 0.44% spray-dried whole egg from hyper-immunized hens (IEGG); or 5.00% SDBP. Results of Exp. 1 indicated pigs fed SDPP diets had greater (P < 0.05) ADG and ADFI at d 7 and 15 compared with pigs fed SPC or APP diets. Gain:feed at d 7 was higher (P < 0.05) for pigs fed diets with SDPP compared with other diets. Average BW at d 7 was greater (P < 0.05) for pigs fed diets with SDPP compared to other diets and pigs fed the 5.00% SDPP diet had greater BW at d 15 compared to diets without SDPP. At d 28 BW was greater (P < 0.05) for pigs fed the 2.50% SDPP diet compared with pigs fed diets with SPC, 0.33% APP, or 1.00% APP. Performance of pigs fed the SPC diet did not differ from APP diets at any period of the study. In Exp. 2, pigs fed the SDBP diet had greater (P < 0.05) BW, ADG, and ADFI at d 7 and 14 compared with pigs fed the other diets. Gain:feed did not differ significantly among diets. Average daily gain and ADFI of pigs did not differ among diets that did not contain SDBP. In conclusion, during the initial 2 wk post-weaning, pigs housed in unsanitary pens and fed non-medicated diets with APP in Exp. 1, or APP, EHSY, CB, or IEGG in Exp. 2 had equivalent performance to pigs fed SPC; however, performance of pigs fed diets with the alternatives was not equivalent to diets containing SDPP in Exp. 1 or SDBP in Exp. 2.


title: Novel use of home pulse oximetry monitoring in COVID‐19 patients discharged from the emergency department identifies need for hospitalization

text: OBJECTIVES: Our objective was to evaluate patient‐reported oxygen saturation (SpO(2)) using pulse oximetry as a home monitoring tool for patients with initially non‐severe COVID‐19 to identify need for hospitalization. METHODS: Patients were enrolled at the emergency department (ED) and outpatient testing centers. Each patient was given a home pulse oximeter and instructed to record their SpO(2) every eight hours. Patients were instructed to return to the ED for sustained home SpO(2) <92% or if they felt they needed emergent medical attention. Relative risk was used to assess the relation between hospitalization and home SpO(2) <92% in COVID‐19 positive patients. RESULTS: We enrolled 209 patients with suspected COVID‐19, of which 77 patients tested positive for COVID‐19 and were included. Subsequent hospitalization occurred in 22/77 (29%) patients. Resting home SpO(2) <92% was associated with an increased likelihood of hospitalization compared to SpO(2) ≥92% [RR 7.0 (95% CI 3.4 – 14.5), p‐value <0.0001]. Home SpO2 <92% was also associated with increased risk of ICU admission, ARDS and septic shock. In our cohort, 50% of patients who ended up hospitalized only returned to the ED for incidental finding of low home SpO(2) without worsening of symptoms. One‐third (33%) of non‐hospitalized patients stated they would have returned to the ED if they did not have a pulse oximeter to reassure them at home. CONCLUSIONS: This study found that home pulse oximetry monitoring identifies need for hospitalization in initially non‐severe COVID‐19 patients when a cut off of SpO(2) 92% is used. Half of patients who ended up hospitalized had SpO(2) <92% without worsening symptoms. Home SpO(2) monitoring also reduces unnecessary ED revisits.


Cancer has not gone away: A primary care perspective to support a balanced approach for timely cancer diagnosis during COVID‐19


title: Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase

text: The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2′-O-ribose methyltransferase (2′-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2′-O-MTase methylates the ribose 2′-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (ΔG), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (ΔG = −9.8 kcal/mol) & Raltegravir (ΔG = −7.8 kcal/mol) for 3CLpro and Dolutegravir (ΔG = −9.4 kcal/mol) and Bictegravir (ΔG = −8.4 kcal/mol) for 2′-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma


title: Disability-Adjusted Life Years for Communicable Disease in the Korean Burden of Disease Study 2012

text: Globally, the incidence of communicable diseases has decreased compared to non-communicable diseases. However, chronic communicable diseases such as HIV/AIDS and tuberculosis persist worldwide. Furthermore, emerging new infections such as H1N1 influenza pose a new threat to public health. However, most studies have focused on non-communicable diseases because of their increasing incidence, with fewer studies investigating communicable diseases. Therefore, we estimated the burden of communicable diseases in Korea using national representative 2012 data. To estimate the disability-adjusted life years (DALY), we used cause of death data from the Statistics Korea to estimate the years of life lost (YLL), applied the Korean garbage code algorithm, and used national claims data from the National Health Insurance Service (NHIS) to estimate years lived with disability (YLD). In 2012, the total DALYs of communicable disease were 445 per 100,000, with 129 YLLs per 100,000 and 316 YLDs per 100,000. The total DALYs in men were 468 per 100,000, greater than the 422 per 100,000 DALYs seen in women. The DALYs of lower respiratory infections were the highest value among communicable diseases at 143/100,000 DALYs followed by tuberculosis and upper respiratory infections. The 40-49 years old age group had the largest number of total DALYs. In contrast, the over 80 years old age group had the largest number of total DALYs per 100,000 followed by the 70-79 and 0-9 years old age groups. These results enable the prioritization of interventions related to communicable diseases and can be used for evidence-based public health policies.


title: Characteristics of COVID-19 Community Practice Declines in Non-Invasive Diagnostic Imaging Professional Work

text: Purpose The operational and financial impact of the widespread COVID-19 curtailment of imaging services on radiology practices is unknown. We aimed to characterize recent COVID-19 related community practice non-invasive diagnostic imaging professional work declines. Methods Using imaging metadata from nine community radiology practices across the United States between January 2019 and May 2020, we mapped work relative value unit (wRVU) weighted stand-alone non-invasive diagnostic imaging service codes to both modality and body region. Weekly 2020 vs. 2019 wRVU changes were analyzed by modality, body region, and site of service. Practice share Chi-square testing was performed. Results Aggregate weekly wRVUs ranged from a high of 120,450 (February 2020) to a low of 55,188 (April 2020). During that -52% wRVU nadir, outpatient declines were greatest (-66%). All practices followed similar aggregate trends in the distribution of wRVUs between each 2020 vs. 2019 week (p=0.96-0.98). As a percentage of total all-practice wRVUs, declines in CT (20,046/63,992; 31%) and radiography/fluoroscopy (19,196; 30%) were greatest. By body region, declines in abdomen/pelvis (16,203; 25%) and breast (12,032; 19%) imaging were greatest. Mammography (-17%) and abdominal/pelvic CT (-14%) accounted for the largest shares of total all-practice wRVU reductions. Across modality-region groups, declines were far greatest for mammography (-92%). Conclusions Substantial COVID-19 related diagnostic imaging work declines were similar across community practices and disproportionately impacted mammography. Decline patterns could facilitate pandemic second wave planning. Overall implications for practice workflows, practice finances, patient access, and payment policy are manifold.


title: A review of vaccine research and development: Human acute respiratory infections()

text: Worldwide, acute respiratory infections (ARIs) constitute the leading cause of acute illnesses, being responsible for nearly 4 million deaths every year, mostly in young children and infants in developing countries. The main infectious agents responsible for ARIs include influenza virus, respiratory syncytial virus (RSV), parainfluenza virus type 3 (PIV-3), Streptococcus pneumoniae and Haemophilus influenzae. While effective vaccines against influenza, H. influenzae type b (Hib) and S. pneumoniae infections have been available for several years, no vaccine is available at present against illnesses caused by RSV, PIV-3, metapneumovirus or any of the three novel coronaviruses. In addition, the threat constituted by the multiple outbreaks of avian influenza during the last few years is urgently calling for the development of new influenza vaccines with broader spectrum of efficacy, which could provide immunity against an avian influenza virus pandemic. This article reviews the state of the art in vaccine R&D against ARIs and attempts to address these basic public health questions.


title: Real-world comparison of two molecular methods for detection of respiratory viruses

text: BACKGROUND: Molecular polymerase chain reaction (PCR) based assays are increasingly used to diagnose viral respiratory infections and conduct epidemiology studies. Molecular assays have generally been evaluated by comparing them to conventional direct fluorescent antibody (DFA) or viral culture techniques, with few published direct comparisons between molecular methods or between institutions. We sought to perform a real-world comparison of two molecular respiratory viral diagnostic methods between two experienced respiratory virus research laboratories. METHODS: We tested nasal and throat swab specimens obtained from 225 infants with respiratory illness for 11 common respiratory viruses using both a multiplex assay (Respiratory MultiCode-PLx Assay [RMA]) and individual real-time RT-PCR (RT-rtPCR). RESULTS: Both assays detected viruses in more than 70% of specimens, but there was discordance. The RMA assay detected significantly more human metapneumovirus (HMPV) and respiratory syncytial virus (RSV), while RT-rtPCR detected significantly more influenza A. We speculated that primer differences accounted for these discrepancies and redesigned the primers and probes for influenza A in the RMA assay, and for HMPV and RSV in the RT-rtPCR assay. The tests were then repeated and again compared. The new primers led to improved detection of HMPV and RSV by RT-rtPCR assay, but the RMA assay remained similar in terms of influenza detection. CONCLUSIONS: Given the absence of a gold standard, clinical and research laboratories should regularly correlate the results of molecular assays with other PCR based assays, other laboratories, and with standard virologic methods to ensure consistency and accuracy.


title: Therapists join national effort to help essential workers

text: Employees deemed “essential” workers (i.e., health care professionals, first responders, service industry employees, truck drivers, military and many others on the front line who are not able to work from their homes and risk exposure to COVID‐19 so that others could stay at home) can now have access to free or reduced‐fee online therapy sessions.


title: Clinical features of pediatric patients with coronavirus disease (COVID-19)

text: Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10–26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1–23 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.


title: Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine

text: Abstract The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (CoV), a type I transmembrane envelope glycoprotein, consists of S1 and S2 domains responsible for virus binding and fusion, respectively. The S1 contains a receptor-binding domain (RBD) that can specifically bind to angiotensin-converting enzyme 2 (ACE2), the receptor on target cells. Here we show that a recombinant fusion protein (designated RBD-Fc) containing 193-amino acid RBD (residues 318–510) and a human IgG1 Fc fragment can induce highly potent antibody responses in the immunized rabbits. The antibodies recognized RBD on S1 domain and completely inhibited SARS-CoV infection at a serum dilution of 1:10,240. Rabbit antisera effectively blocked binding of S1, which contains RBD, to ACE2. This suggests that RBD can induce highly potent neutralizing antibody responses and has potential to be developed as an effective and safe subunit vaccine for prevention of SARS.


Porcine Deltacoronavirus, Thailand, 2015


title: SARS-CoV-Encoded Small RNAs Contribute to Infection-Associated Lung Pathology

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) causes lethal disease in humans, which is characterized by exacerbated inflammatory response and extensive lung pathology. To address the relevance of small non-coding RNAs in SARS-CoV pathology, we deep sequenced RNAs from the lungs of infected mice and discovered three 18–22 nt small viral RNAs (svRNAs). The three svRNAs were derived from the nsp3 (svRNA-nsp3.1 and -nsp3.2) and N (svRNA-N) genomic regions of SARS-CoV. Biogenesis of CoV svRNAs was RNase III, cell type, and host species independent, but it was dependent on the extent of viral replication. Antagomir-mediated inhibition of svRNA-N significantly reduced in vivo lung pathology and pro-inflammatory cytokine expression. Taken together, these data indicate that svRNAs contribute to SARS-CoV pathogenesis and highlight the potential of svRNA-N antagomirs as antivirals.


title: Effects of an experimentally induced rhinovirus cold on sleep, performance, and daytime alertness

text: Abstract Study objectives: There is accumulating evidence that the common cold produces impairments in psychomotor vigilance. This has led some investigators to hypothesize that such illnesses may also have disruptive effects on sleep. While several self-report studies suggest that viral illness may influence sleep parameters, no studies have assessed polysomnographically recorded sleep following viral infections. Design: Parallel control group comparison. Setting: Sleep laboratory in a large urban medical center. Participants: Twenty-one men and women with susceptibility to the rhinovirus type 23. Interventions: Nasal inoculation with rhinovirus type 23. Measurements: Polysomnographically recorded sleep for five nights (2300–0700 h) post-viral inoculation. Twice daily (1030 and 1430 h) performance assessment during each experimental day using auditory vigilance and divided attention tasks. A multiple sleep latency test (MSLT) was performed daily for the duration of the study. Results: In symptomatic individuals, total sleep time decreased an average of 23 min, consolidated sleep decreased an average of 36 min, and sleep efficiency was reduced by an average of 5% during the active viral period (experimental days/nights 3–5) compared with the incubation period. Psychomotor performance was impaired. These changes were significantly greater than those observed in asymptomatic individuals. Conclusions: The common cold can have detrimental effects on sleep and psychomotor performance in symptomatic individuals during the initial active phase of the illness.


title: In vivo Biodistribution of a Highly Attenuated Recombinant Vesicular Stomatitis Virus Expressing HIV-1 Gag Following Intramuscular, Intranasal, or Intravenous Inoculation

text: Recombinant vesicular stomatitis viruses (rVSVs) are being developed as potential HIV-1 vaccine candidates. To characterize the in vivo replication and dissemination of rVSV vectors in mice, high doses of a highly attenuated vector expressing HIV-1 Gag, rVSV(IN)- N4CT9-Gag1, and a prototypic reference virus, rVSV(IN)-HIVGag5, were delivered intramuscularly (IM), intranasally (IN), or intravenously (IV). We used quantitative, real-time RT-PCR (Q-PCR) and standard plaque assays to measure the temporal dissemination of these viruses to various tissues. Following IM inoculation, both viruses were detected primarily at the injection site as well as in draining lymph nodes; neither virus induced significant weight loss, pathologic signs, or evidence of neuroinvasion. In contrast, following IN inoculation, the prototypic virus was detected in all tissues tested and caused significant weight loss leading to death. IN administration of rVSV(IN)- N4CT9-Gag1 resulted in detection in numerous tissues (brain, lung, nasal turbinates, and lymph nodes) albeit in significantly reduced levels, which caused little or no weight loss nor any mortality. Following IV inoculation, both prototypic and attenuated viruses were detected by Q-PCR in all tissues tested. In contrast to the prototype, rVSV(IN)-N4CT9-Gag1 viral loads were significantly lower in all organs tested, and no infectious virus was detected in the brain following IV inoculation, despite the presence of viral RNA. These studies demonstrated significant differences in the biodistribution patterns of and the associated pathogenicity engendered by the prototypic and attenuated vectors in a highly susceptible host.


title: Diagnosis of community-acquired acute respiratory illness: From conventional microbiological methods to molecular detection (multiplex)

text: Abstract Investigations of the etiologic agents of community-acquired acute respiratory illness may lead to better treatment decisions and patient outcomes. In a routine care setting, we assessed the diagnostic performance of a multiplex PCR assay with respect to conventional microbiological methods, in a continuous series of adult cases of community-acquired acute respiratory illness. We enrolled 279 adult patients hospitalised for community-acquired acute respiratory illness at Tours University Hospital during the winter of 2011–2012. Respiratory samples (mostly nasopharyngeal aspirates) were studied prospectively by indirect immunofluorescence assay and multiplex PCR, that enable detection of 8 viruses and 21 respiratory pathogens respectively. In total, 255 of the 279 (91.4%) samples had interpretable results by both methods. At least one respiratory pathogen was detected by multiplex PCR in 171 specimens (65%). Overall, 130 (76%) of the 171 positive samples were positive for only one respiratory pathogen, 37 (22%) samples were positive for two pathogens and four (2%) were positive for three pathogens. With indirect immunofluorescence assay, a respiratory virus was detected in 27 of the 255 (11%) specimens. Indirect immunofluorescence assay detected some of the influenza virus A (15/51, 29%) infections identified by multiplex PCR and some (7/15, 47%) human metapneumovirus and (5/12, 42%) respiratory syncytial virus infections, but it did not detect all the adenovirus infections. Thus, access to multiplex molecular assays improves the diagnostic spectrum and accuracy over conventional methods, increasing the frequency of identification of the respiratory pathogens involved in community-acquired acute respiratory illness.


EV71 vaccines: a milestone in the history of global vaccine development